Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Testing the Addition of the Chemotherapy Drug Lomustine (Gleostine®) to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Methylated Glioblastoma
This phase III trial compares the effect of adding lomustine to temozolomide and radiation
therapy versus temozolomide and radiation therapy alone in shrinking or stabilizing newly
diagnosed MGMT methylated glioblastoma. Chemotherapy drugs, such as lomustine and
temozolomide, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy
uses high energy photons to kill tumor cells and shrink tumors. Adding lomustine to usual
treatment of temozolomide and radiation therapy may help shrink and stabilize glioblastoma.
• STEP 1 REGISTRATION: No known IDH mutation. (If tested before step 1 registration,
patients known to have IDH mutation in the tumor on local or other testing are
ineligible and should not be registered)
• STEP 1 REGISTRATION: Availability of formalin-fixed paraffin-embedded (FFPE) tumor
tissue block and hematoxylin and eosin (H&E) stained slide to be sent for central
pathology review for confirmation of histology and MGMT promoter methylation status.
Note that tissue for central pathology review and central MGMT assessment must be
received by the NYU Center for Biospecimen Research and Development (CBRD) on or
before postoperative calendar day 23. If tissue cannot be received by postoperative
calendar day 23, then patients may NOT enroll on this trial as central pathology
review will not be complete in time for the patient to start treatment no later than 6
weeks following surgery. Results of central pathology review and central MGMT analysis
will generally be conveyed to NRG Oncology within 10 business days of receipt of
tissue. Note: In the event of an additional tumor resection(s), tissue must be
received within 23 days of the most recent resection and the latest resection must
have been performed within 30 days after the initial resection. Surgical resection is
required; stereotactic biopsy alone is not allowed because it will not provide
sufficient tissue for MGMT analysis
• STEP 1 REGISTRATION: Contrast-enhanced brain MRI within 4 days after surgery
• Magnetic resonance imaging (MRI) with Axial T2 weighted FLAIR{preferred} or T2
TSE/FSE and 3D contrast-enhanced T1 sequences are required.
• 3-dimensional (3D) pre contrast-enhanced T1 sequences are strongly suggested
• STEP 1 REGISTRATION: Willing to use highly effective method of contraception for
participants of childbearing potential (participants who may become pregnant or who
may impregnate a partner) during therapy and for 6 months after completing treatment;
this inclusion is necessary because the treatment in this study may be significantly
teratogenic
• STEP 1 REGISTRATION: The patient or a legally authorized representative must provide
study-specific informed consent prior to study entry and, for patients treated in the
United States (U.S.), authorization permitting release of personal health information
• STEP 2 REGISTRATION: Histopathologically proven diagnosis of glioblastoma (or
gliosarcoma as a subtype of glioblastoma) confirmed by central pathology review
• STEP 2 REGISTRATION: MGMT promoter with methylation confirmed by central pathology
review (See Section 10 for details). Note: Patients with tissue that is insufficient
or inadequate for analysis, fails MGMT testing, or has indeterminate or unmethylated
MGMT promoter are excluded. Patients with unmethylated MGMT may be considered for
enrollment on NRG-BN007
• STEP 2 REGISTRATION: IDH mutation testing by at least one method (such as
immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and
no mutation must be found (i.e IDH wildtype). (If a mutation is identified then the
patient will be ineligible and must be registered as ineligible at Step 2.)
• STEP 2 REGISTRATION: History/physical examination within 28 days prior to Step 2
registration
• STEP 2 REGISTRATION: Karnofsky performance status (KPS) >= 70 within 28 days prior to
Step 2 registration
• STEP 2 REGISTRATION: Neurologic function assessment within 28 days prior to Step 2
registration
• STEP 2 REGISTRATION: Age 18-70 years
• STEP 2 REGISTRATION: Hemoglobin >= 10 g/dl (Note: the use of transfusion or other
intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable)
• STEP 2 REGISTRATION: Leukocytes >= 2,000/mm^3
• STEP 2 REGISTRATION: Absolute neutrophil count >= 1,500/mm^3
• STEP 2 REGISTRATION: Platelets >= 100,000/mm^3
• STEP 2 REGISTRATION: Total bilirubin =< 1.5 x institutional/lab upper limit of normal
(ULN)
• STEP 2 REGISTRATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic
transaminase [SGOT]) =< 2.5 x ULN
• STEP 2 REGISTRATION: Alanine aminotransferase (ALT) (serum glutamate pyruvate
transaminase [SGPT]) =< 2.5 x ULN
• STEP 2 REGISTRATION: Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >=
50 mL/min (if using the Cockcroft-Gault formula
• STEP 2 REGISTRATION: For patients with evidence of chronic hepatitis B virus (HBV)
infection, the HBV viral load must be undetectable on suppressive therapy, if
indicated
• Note: Known positive test for hepatitis B virus surface antigen (HBV sAg)
indicating acute or chronic infection would make the patient ineligible unless
the viral load becomes undetectable on suppressive therapy. Patients who are
immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible
(e.g. patients immunized against hepatitis B)
• STEP 2 REGISTRATION: For patients with a history of hepatitis C virus (HCV) infection
must have been treated and cured. For patients with HCV infection who are currently on
treatment, they are eligible if they have an undetectable HCV viral load
• Note: Known positive test for hepatitis C virus ribonucleic acid (HCV ribonucleic
acid [RNA]) indicating acute or chronic infection would make the patient
ineligible unless the viral load becomes undetectable on suppressive therapy
• STEP 2 REGISTRATION: Known human immunodeficiency virus (HIV) infected patients on
effective anti-retroviral therapy with undetectable viral load within 6 months prior
to step 2 registration are eligible for this trial. Testing is not required for entry
into protocol
• STEP 2 REGISTRATION: Negative serum or urine pregnancy test (in persons of
childbearing potential) within 7 days prior to Step 2 registration
• Childbearing potential is defined as any person who has experienced menarche and
who has not undergone surgical sterilization (hysterectomy or bilateral
oophorectomy) or who is not postmenopausal
Exclusion Criteria:
• STEP 2 REGISTRATION: Prior therapy for tumor except for resection. For example, prior
chemotherapy, immunotherapy, or targeted therapy for GBM or lower grade glioma is
disallowed (including but not limited to temozolomide, lomustine, bevacizumab, any
viral therapy, ipilimumab or other CTLA-4 antibody, PD-1 antibody, CD-137 agonist,
CD40 antibody, PDL-1 or 2 antibody, vaccine therapy, polio or similar viral injection
as treatment for the tumor, and/or any other antibody or drug specifically targeting
T-cell co-stimulation or immune checkpoint pathways) as is prior Laser interstitial
thermal therapy (LITT), Gliadel wafer, radiotherapy, radiosurgery, vaccine or other
immunotherapy, brachytherapy, or convection enhanced delivery
• Note: 5-aminolevulinic acid (ALA)-mediated fluorescent guided resection (FGR)
photodynamic therapy (PDT) or fluorescein administered prior to/during surgery to
aid resection is not exclusionary and is not considered a chemotherapy or
intracerebral agent
• STEP 2 REGISTRATION: Current or planned treatment with any other investigational
agents for the study cancer
• STEP 2 REGISTRATION: Definitive clinical or radiologic evidence of metastatic disease
outside the brain
• STEP 2 REGISTRATION: Prior invasive malignancy (except non-melanomatous skin cancer,
cervical cancer in situ and melanoma in situ) unless disease free for a minimum of 2
years
• STEP 2 REGISTRATION: Prior radiotherapy to the head or neck that would result in
overlap of radiation therapy fields
• STEP 2 REGISTRATION: Pregnancy and individuals unwilling to discontinue nursing due to
the potential teratogenic effects and potential risk for adverse events in nursing
infants
• STEP 2 REGISTRATION: History of allergic reactions attributed to compounds of similar
chemical or biologic composition to temozolomide or lomustine
• STEP 2 REGISTRATION: History of pulmonary fibrosis
• STEP 2 REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection requiring IV antibiotics, IV antiviral, or IV
antifungal treatment
• Symptomatic congestive heart failure, defined as New York Heart Association
Functional Classification III/IV (Note: Patients with known history or current
symptoms of cardiac disease, or history of treatment with cardiotoxic agents,
should have a clinical risk assessment of cardiac function using the New York
Heart Association Functional Classification)
• Unstable angina pectoris within 6 months prior to Step 2 registration
• Uncontrolled cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study
requirements
• Participant is within the approved age range as per labeling recommendations.
• Participant is either on existing Epidiolex therapy for treatment of a seizure
disorder or is to be started on Epidiolex for treatment of an Food and Drug
Administration (FDA)-approved indication.
• Participant is willing to refrain from strenuous exercise 48 to 72 hours prior to all
study visits with the exception of unscheduled visits.
• Any non-pharmacological therapies (e.g., ketogenic diet) must also be stable up to 4
weeks prior to Screening Visit and expected to be stable throughout the duration of
the study.
Exclusion Criteria:
• Participant is currently using or within 3 months of screening has used recreational
or medicinal cannabis, or synthetic cannabinoid-based medications, not including
Epidiolex if currently prescribed.
• Participant is not planning to abstain from using recreational cannabinoids or
medicinal cannabis, or synthetic cannabinoid-based medications during the study.
• Female participant is pregnant (positive pregnancy test), lactating or planning
pregnancy during the course of the study and for 3 months thereafter.
• Participant has any other significant disease or disorder which, in the opinion of the
investigator, may either put the participant, other participants, or site staff at
risk because of participation in the study, may influence the result of the study, or
may affect the participant's ability to take part in the study
• Participant has diseases or disorders which are associated with known severe liver
fibrosis with a FibroScan score of ≥ 6.5 Kilopascals.
• Positive serology panel (including hepatitis B surface antigen and hepatitis C virus
antibody) and/or positive human immunodeficiency virus antibody/p24 antigen screens at
screening.
• Following a physical examination, if the participant has any abnormalities that, in
the opinion of the investigator, would prevent the participant from safe participation
in the study.
• Participant has significantly impaired hepatic function at Screening Visit alanine
aminotransferase or aminotransferase > 3 x upper limit of normal (ULN), and total
bilirubin > 2 x ULN or international normalized ratio > 1.5.
• Participant is planning to have epilepsy surgery or other major surgery within five
years.
• Participant has or plans to have any medical device implanted that is contraindicated
for use with FibroScan, with the investigator consulting with the Sponsor as needed.
• Participation in any clinical trial involving an investigational medicinal product
within 3 months prior to the Screening Visit or at any point during this study.
• Histologically or cytologically documented locally advanced or metastatic solid tumor
malignancy.
• Progressed or was intolerant to all available therapies known to confer clinical
benefit appropriate for their tumor type, and for which the patient was eligible and
willing to receive, or refused SOC treatments that are perceived to have marginal
clinical benefit.
• Adequate bone marrow, kidney and liver function.
• Performance status of 0 or 1.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1
except for AEs not constituting a safety risk by Investigator judgement.
Exclusion Criteria:
• Prior treatment targeting ILT2 and/or ILT4 or targeting HLA-G.
Drug: NGM707, Drug: NGM707 plus pembrolizumab, Drug: NGM707, Drug: NGM707, Drug: NGM707, Drug: NGM707 plus pembrolizumab, Drug: NGM707 plus pembrolizumab
Esophageal Cancer, Breast Cancer, Melanoma, Gastric Cancer, Colorectal Cancer, Ovarian Cancer, Glioblastoma, Cervical Cancer, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Mesothelioma, Cholangiocarcinoma, Pancreatic Ductal Adenocarcinoma, Brain and Nervous System, Breast - Female, Breast - Male, Kidney, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Skin, Ovary, Pancreas, Squamous Cell Carcinoma of Head and Neck, Endocervical Cancer
Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias
Spinocerebellar ataxias (SCA) are genetic neurological diseases that cause imbalance, poor
coordination, and speech difficulties. There are different kinds of SCA and this study will
focus on types 1, 2,3, and 6 (SCA 1, SCA 2, SCA 3 , also known as Machado-Joseph disease and
SCA 6). The diseases are rare, slowly progressive, cause increasingly severe neurological
difficulties and are variable across and within genotypes. The purpose of this research study
is to bring together a group of experts in the field of SCA for the purpose of learning more
about the disease.
The research questions are:
1. How does your disease progress over time?
2. What are the best ways to measure the progression?
3. Do some genes, other than the gene that is abnormal in your disease, have any effect on
the way the disease behaves?
This is a nationwide study and we expect that 800 patients will participate all over the USA.
The participants will be in the study for an indeterminate period of time. Study visits will
be done every 6 or 12 months depending on the participating site.
• Presence of symptomatic ataxic disease
• Definite molecular diagnosis of SCA 1, 2,3,or 6 either in the subject or another
affected family member
• Willingness to participate in the study and ability to give informed consent.
• Age 6 years and above
Exclusion Criteria:
• Known recessive, X-linked and mitochondrial ataxias
• Exclusion of SCA 1, 2, 3 and 6 by previous DNA testing,
• A lack of willingness to participate in the study
Genetic: All Participants
Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia Type 3, Spinocerebellar Ataxia Type 6
Spinocerebellar Ataxia, Natural History, Genetic Modifiers, DNA testing
The brain networks controlling movement are complex, involving multiple areas of the brain.
Some neurological disorders, like Parkinson's disease (PD) and essential tremor (ET), cause
abnormalities in these brain networks. Deep brain stimulation is a treatment that is used to
treat these types of neurological diseases and is thought to help patients by modulating
brain networks responsible for movement. Levodopa medication is also used to modulate this
brain networks in patients with PD. The overall objective is to develop a unified theory of
basal ganglia thalamocortical (BGTC) circuit dynamics that accounts for disease
symptomatology, movement, and their inter-relationship. The underlying hypothesis, is that
the rigidity and bradykinesia of PD are fundamentally related to excessive functional
coupling across nodes in the BGTC motor circuit impeding effective information flow. In this
research, the investigator will take advantage of the unique opportunity provided by awake
deep brain stimulation surgery to learn more about how the brain functions in a diseased
state and how deep brain stimulation changes these networks to make movement more normal. The
investigator will simultaneously assess cortical and subcortical electrophysiology in
relation to clinical symptoms and behavioral measures and in response to deep brain
stimulation, cortical stimulation, and pharmacologic therapy in patients undergoing Deep
Brain Stimulation (DBS) implantation surgery.
• Diagnosis of Parkinson's disease or Essential Tremor who have been recommended to
undergo deep brain stimulation for management of their movement disorder
• Preoperative MRI without evidence of cortical or subdural adhesions or vascular
abnormalities
• Willingness and ability to cooperate during conscious operative procedure for up to 40
minutes
Exclusion Criteria:
• Patients with recent use (within one week) of anticoagulant or antiplatelet agents
• Neurocognitive testing indicating amnestic cognitive deficits
Drug: Inbrija, Other: Subcortical Stimulation
Parkinson Disease, Essential Tremor, Brain and Nervous System
deep brain stimulation, levodopa medication, motor cortex, basal ganglia, thalamus
Mapping the Phenotype in Adults With Phelan-McDermid Syndrome
The protocol aims to comprehensively define the phenotype of Phelan-McDermid Syndrome and to
identify potential genetic factors, which may play a role in the variability of the disease's
outcomes. The first aim involves a physical exam, a neurological exam, collection of medical
history information, a clinical genetic evaluation, blood work and neuropsychological
assessments. If clinically indicated, the protocol collects information from medical tests.
These medical tests may include electrocardiography, echocardiography, renal ultrasonography,
and renal ultrasound.
• Participant is 22 years of age and older at the time of enrollment
• Participant has been diagnosed with pathogenic deletions or mutations of the SHANK3
gene
• Participant is proficient in English
• Participant provided consent
Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females (EMRSHN)
The goal of this project is to test our central hypothesis that changes in sex hormone
concentration result in changes to the basic elements of motor control - at multiple levels,
from the musculotendinous unit to motor control circuitry. Under Aim 1 the investigator will
determine the influence of sex hormone fluctuations on the muscle stretch reflex during
active and passive states, and the time lag between hormone concentration changes and the
reflex response. The investigator will use a technically simple assessment that could be
implemented in the field. Under Aim 2 the investigator will determine the influence of sex
hormone fluctuations on spinal motor neuron excitability using H-reflex as a probe and the
simultaneous change in the muscle mechanics using muscle twitch response. Aims 1 & 2 will
include a focus on the differential role of oral contraceptives. In Aim 3 the investigator
will use paired-pulse transcranial magnetic stimulation during active contraction to
determine the influence of sex hormone fluctuation.
• Females: ages 18-39 years, who are eumenorrheic (regular monthly cycles of 24-35 days)
or on a stable hormonal contraceptive regimen for 6 months (oral, transdermal or
vaginal), no history of pregnancy, moderately active (less than 7 hours of vigorous
physical activity per week)
• Males: Ages 18-39
Exclusion Criteria:
• History of musculoskeletal or orthopedic injury of the spine, hip, knee, ankle or
foot, history of neurological injury of the peripheral or central nervous system,
current smoker, history of disordered eating, history of stress fracture in the lower
limb, history of a connective tissue disorder (Marfan's syndrome, Ehlers-Danlos
disease).
• For female participants only: Point of care screening for anemia will be completed,
and individuals with hemoglobin levels <11.6 g/dl will be excluded from participating
in the study.
• Specific exclusion criteria for TMS (male and female): pacemaker, metal implants in
the head region, history of epilepsy or seizures, skull fractures or skull deficits,
concussion within the last 6 months, unexplained recurring headaches, medications that
lower seizure threshold, and pregnancy.
• Additional exclusion criteria for female participants: History of menstrual
dysfunction (primary or secondary amenorrhea, oligomenorrhea, anovulatory cycles,
polycystic ovarian disease), current or past pregnancy, started or stopped taking oral
contraceptives within the previous 6 months, exercise vigorously more than 7 hours per
week or currently participating in competitive level sports. The reason for excluding
highly active or competitive athletes is due to the high rate of undiagnosed menstrual
dysfunction in females of this population.
• This study will not include: adults unable to consent, Individuals who are not yet
adults (infants, children, teenagers), pregnant women or prisoners.
Device: Transcranial Magnetic Stimulation Device
Role of Sex Hormones Along the Neuromechanical Axis
Sex Hormones
UT Southwestern; Parkland Health & Hospital System
General anesthesia (GA) is a medically induced state of unresponsiveness and unconsciousness,
which millions of people experience every year. Despite its ubiquity, a clear and consistent
picture of the brain circuits mediating consciousness and responsiveness has not emerged.
Studies to date are limited by lack of direct recordings in human brain during medically
induced anesthesia. Our overall hypothesis is that the current model of consciousness,
originally proposed to model disorders and recovery of consciousness after brain injury, can
be generalized to understand mechanisms of consciousness more broadly. This will be studied
through three specific aims. The first is to evaluate the difference in anesthesia
sensitivity in patients with and without underlying basal ganglia pathology. Second is to
correlate changes in brain circuitry with induction and emergence from anesthesia. The third
aim is to evaluate the effects of targeted deep brain stimulation on anesthesia induced loss
and recovery of consciousness. This study focuses on experimentally studying these related
brain circuits by taking advantage of pathological differences in movement disorder patient
populations undergoing deep brain stimulation (DBS) surgery. DBS is a neurosurgical procedure
that is used as treatment for movement disorders, such as Parkinson's disease and essential
tremor, and provides a mechanism to acquire brain activity recordings in subcortical
structures. This study will provide important insight by using human data to shed light on
the generalizability of the current model of consciousness. The subject's surgery for DBS
will be prolonged by up to 40 minutes in order to record the participant's brain activity and
their responses to verbal and auditory stimuli.
• Willingness and ability to cooperate during conscious operative procedure for up to 40
minutes
• Clinical diagnosis of Parkinson's disease or essential tremor
• Preoperative MRI without evidence of cortical or subdural adhesions or vascular
abnormalities
Exclusion Criteria:
• Patients with recent use (within one week) of anticoagulant or antiplatelet agent use
• Neurocognitive testing indicating amnestic cognitive deficits
• History of intolerance of propofol or medical indications to use an anesthetic other
than propofol
Drug: Propofol
Parkinson Disease, Anesthesia, Essential Tremor, Brain and Nervous System, Loss of Consciousness
general anesthesia, deep brain stimulation, basal ganglia, thalamus, sensorimotor cortex
1. Patient or legally authorized representative provides written authorization and/or
consent.
2. Patient is enrolled in the LAANTERN trial and had an epilepsy diagnosis without the
presence of a malignant brain tumor.
3. Patient is 16 years of age or older.
4. Patient has completed a baseline comprehensive neuropsychological assessment with a
neuropsychologist.
Exclusion Criteria:
1. Patient does not complete the index LITT procedure as specified in the LAANTERN
registry.
Device: Neuroblate System
Brain and Nervous System, Cognitive Change
Quality of Life, Neuropsychological Test Scores, Visual Field
The purpose of this study is to (1) investigate the effect of known dystonia-causing
mutations on brain structure and function, to (2) identify structural brain changes that
differ between clinical phenotypes of dystonia, and to (3) collect DNA, detailed family
history, and clinical phenotypes from patients with idiopathic dystonia with the goal of
identifying new dystonia-related genes. Investigators will be recruiting both healthy control
subjects and subjects with any form of dystonia. For this study there will be a maximum of
two study visit involving a clinical assessment, collection of medical and family history,
task training session, an MRI using the learned tasks, and finally a blood draw for genetic
analysis. In total, these visits will take 3-5 hours. If the dystonia subjects receive
botulinum toxin injections for treatment, the participants and their matched controls will be
asked to come for a second visit.
General Exclusion (both Dystonia and Control groups):
• Metal in any part of the body (including metal injury to the eye) OR carrying a
medical device incompatible with MRI (e.g., metal implants such as surgical clips or
pacemakers) OR positive screening per UTSW MRI screening form
• Claustrophobia
• Non-fluent English
• Weight incompatible with MRI safety
• History of head trauma with neurological sequelae, including multiple concussions
and/or history of stroke
• Pregnancy
• Serious medical illness or history of serious medical illness, including cancer that
was treated with radiation or chemotherapy, heart attack, or a known history of HIV-1
+ status
• Subjects with Hepatitis C (by Hepatitis C+ titer)
• Subjects with insulin dependent diabetes mellitus (IDDM)
• Severe respiratory compromise
• In the opinion of the investigator, not able to safely participate in this study
Inclusion Criteria:
• Dystonia group
Previous diagnosis of dystonia which include but is not limited to:
• cervical dystonia (50 subjects)
• blepharospasm (25 subjects)
• limb dystonia (50 subjects)
• spasmodic dysphonia (25 subjects)
• segmental dystonia
• multi-focal dystonia
• Any childhood-onset dystonia (25 subjects) Age > 11 years
• Control group:
No prior dystonia diagnosis (175 subjects) Age > 11 years
Exclusion Criteria:
• Dystonia group Prior history of or concurrent neurological or psychiatric diagnosis -
depression and/or anxiety accepted Current use of non-dystonia neuroactive medications
•SSRI/medication for depression and/or anxiety accepted Current use of cervical brace
designed for dystonia treatment Prior structural brain injury
Control group:
History of or current neurological or psychiatric diagnosis •depression and/or anxiety
accepted, but must not be in active phase Current use of any neuroactive medication,
SSRI/medication for depression and/or anxiety accepted
Multimodal Monitoring of Cerebral Autoregulation After Pediatric Brain Injury
Various methods have been studied to evaluate autoregulation. However, there is currently no
universally accepted technique to assess integrity of the cerebral autoregulation
neurovascular system. In the last decade, significant progress has been achieved in
developing methods to assess cerebral autoregulation by quantifying cross-correlation between
spontaneous oscillations in CBF or oxygenation and similar oscillations in arterial blood
pressure.
In this study the investigators will analyze the relationship between spontaneous
fluctuations in mean arterial blood pressure and cerebral blood flow velocity or cerebral
regional oxygenation to investigate two novel methods for measuring cerebral autoregulation,
Transfer Function Analysis and Wavelet Coherence after acute pediatric brain injury.
• Ages 28 days-18 years admitted to the PICU at Children's Medical Center Dallas
• Acute presentation (< 24 hour) onset of neurologic injury
• Acute neurologic injury can be due to any of the following mechanisms:
• Severe accidental or abusive traumatic brain injury
• Severe encephalopathy secondary to cardiac arrest
• Spontaneous intracranial hemorrhage
• Status epilepticus
• Stroke
• Presence of or pending placement of invasive indwelling arterial line for stand
medical care
• Any patient with an ICP monitor placed as standard of care
Exclusion Criteria:
• Patients without an arterial line placed as standard of care
• Patients unable to cooperate with wearing a TCD headpiece device
• Expected death within 24-48 hours
• Inability to place NIRS probes or insonate TCD signal due to massive facial or cranial
injury
• Receiving an inhalational anesthetic agent
• Hemoglobinopathy, myoglobinemia or and hyperbilirubinemia (due to inaccurate NIRS
readings)
Device: Transcranial Doppler
Traumatic Brain Injury, Brain Injuries, Brain Injury, Vascular, Brain and Nervous System
1. Adolescents and adults with previously documented diagnosis of Glut1 Deficiency with
diagnosis genetically confirmed or confirmed by PET scan of the brain.
2. Ages 16 to 65
3. Persons with dental fillings, dental crowns, and short (max.4 cm) dental retainer
wires can be included.
Exclusion Criteria:
1. People or patients with uncontrolled seizure disorder, defined as grand mal (not
absence) seizure in the preceding 3 months.
2. Pregnant females will be excluded. A serum or urine pregnancy test will be
administered to all females of child bearing potential within 24 hours of
administration of the tracer and MRI scan. The pregnancy test will be communicated in
person by the study PI. Positive results in subjects 17 years old or younger will be
disclosed to parent/guardian only.
3. Subjects with typical implanted orthopedic metal in bone may be considered for
inclusion in a 7T scan providing the implant is not within the volume of the radio
frequency coil. The PI and the AIRC Medical Director will discuss each case and
determine eligibility.
4. Persons with ICD, pacemakers, neurostimulators and other such devices will be
excluded.
5. Persons with claustrophobia are excluded.
6. Persons with questionable ferrous implants, bullets, BB's, and shrapnel will be
excluded.
7. Subjects who are not fluent in English will be excluded because immediate cooperation
and the ability to respond to instructions from the investigators are necessary.
Device: Magnetic resonance imaging
Glucose Transporter Type 1 Deficiency Syndrome, Epilepsy, Glut1 Deficiency Syndrome 1, Autosomal Recessive, Glucose Metabolism Disorders, Glucose Transport Defect, Glucose Transporter Protein Type 1 Deficiency Syndrome, Glut1 Deficiency Syndrome 1
Framing Eighteen Coils in Cerebral Aneurysms Trial (FEAT)
This trial is being conducted in order to compare angiographic outcomes in patients
receiving 0.014-0.0155" platinum framing and filling coils (larger diameter coils) versus
those treated solely with coils less than 0.014" (with a standard diameter).
Hypothesis: Angiographic occlusion at follow-up imaging will be more frequent in patients
receiving 0.014-0.0155" platinum coils during embolization compared to those receiving
smaller-diameter coils.
1. Patient presenting with ruptured or unruptured cerebral aneurysm appropriate for
endovascular treatment as determined by the neurovascular treating team
(neurointerventionist and/or neurosurgeon).
2. The neurointerventionist feels that the aneurysm can be safely treated with either
using, or not using, a 0.015-0.0155" platinum coil.
3. Patients are 18-80 years of age (inclusive).
4. Patient must be Hunt and Hess grade 0 to 3.
5. Patient has given fully informed consent to endovascular coiling procedure. If the
patient cannot consent for themselves, appropriate written consent has been sought
from their next of kin or appropriate power of attorney.
6. Aneurysm 6-14 mm in maximum diameter.
7. Patient is willing and able to return for clinical evaluation and follow-up imaging
evaluation (angiography or MRA) at 3-6 months and 12-18 months after endovascular
treatment.
8. The patient has not been previously randomized into this trial or another related
ongoing trial.
9. The aneurysm has not been previously treated by coiling or clipping.
Exclusion Criteria:
1. Patient has more than one aneurysm requiring treatment in the current treatment
session, and only one of those to be treated aneurysms fits the FEAT inclusion
criteria (ie •if either (1) a patient has multiple aneurysms, but only one will be
treated at enrollment; or (2) if two or more aneurysms are treated during the current
treatment session and BOTH are able to be enrolled, then they remain eligible for the
trial). Non-treated additional aneurysms may be treated at a later date with any coil
type that the operator chooses).
2. Target aneurysm has had previous coil treatment or has been surgically clipped.
3. Hunt and Hess score is 4 or 5 after subarachnoid hemorrhage.
4. Inability to obtain informed consent.
5. Medical or surgical co-morbidity such that the patient's life expectancy is less than
2 years.
Procedure: Coil Embolization with larger Diameter Coils, Procedure: Coil Embolization with Standard Diameter Coils
Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD) (MOVE FSHD)
The primary goal of this proposal is to collect motor and functional outcomes specific to
FSHD over time. By collecting measures specific to FSHD, this will help ensure the best level
of clinical care is being provided. Also, the hope is to speed up drug development by gaining
a better understanding of how having FSHD impacts motor function and other health outcomes
(i.e. breathing, wheelchair use, etc.) and how big a change in motor function would be
clinically meaningful to those with FSHD.
Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD) will have approximately 450 FSHD
participants followed for a minimum of 3 years. A subset of MOVE FSHD participants,
approximately 200, will participate in the MOVE+ sub-study which includes whole body MRI and
muscle biopsy.
• Genetically confirmed FSHD (types 1 or 2) or clinical diagnosis of FSHD with
characteristic findings on exam and an affected parent or offspring.
Exclusion Criteria:
• Unwilling or unable to provide informed consent.
• Any other medical condition which in the opinion of the investigator would interfere
with study participation.
Validation of Early Prognostic Data for Recovery Outcome After Stroke for Future, Higher Yield Trials (VERIFY)
VERIFY will validate biomarkers of upper extremity (UE) motor outcome in the acute ischemic
stroke window for immediate use in clinical trials, and explore these biomarkers in acute
intracerebral hemorrhage. VERIFY will create the first multicenter, large-scale, prospective
dataset of clinical, transmagnetic stimulation (TMS), and MRI measures in the acute stroke
time window.
• Age 18 years or older
• Unilateral stroke due to ischemia or intracerebral hemorrhage
• Motor deficits in the acutely affected UE, defined as a Shoulder Abduction and Finger
Extension (SAFE) score ≤ 8 out of 10 points (i.e., excluding full or nearly full motor
strength in both shoulder abduction and finger extension) within 48 to 96 hours of
stroke onset (or time last known well).
• Provision of signed and dated informed consent form within 48 to 96 hours of stroke
onset (or time last known well).
• Stated willingness to comply with all study procedures and availability for the
duration of the study
• Fluent in English or Spanish
Exclusion Criteria:
• UE injury or conditions on paretic side that limited use prior to the stroke.
• Legally blind.
• Dense sensory loss indicated by a score of 2 on NIHSS sensory item
• Unable to abduct the shoulder or extend the fingers of the non-paretic arm/hand/wrist
on verbal command
• Isolated cerebellar stroke
• Bilateral hemisphere acute strokes
• Co-enrollment in a trial of an intervention targeting the incident stroke (acute
treatment or rehabilitation/recovery intervention) after baseline assessments for
VERIFY are initiated
• Known or expected inability to maintain follow-up with study procedures through 90
days
• Cognitive or communication impairment precluding informed consent by the participant.
• Major medical, neurological, or psychiatric condition that would substantially affect
functional status
• Non-cerebrovascular diagnosis associated with unlikely survival at 90 days
• Pregnancy
• Contraindication to noncontrast MRI (i.e., certain metallic implants, metallic foreign
bodies or severe claustrophobia)
• Contraindication to TMS (i.e., cardiac pacemaker or other electronic devices in the
body at or above the level of the seventh cervical vertebra, such as cochlear implant,
cortical stimulator, deep brain stimulator, vagus nerve stimulator, cervical spine
epidural stimulator, or ventriculoperitoneal shunt; Skull defect related to current
stroke; Seizure after onset of current stroke; Seizure within the last 12 months while
taking anti-epileptic medications; Previous serious adverse reaction to TMS)
• Unable to perform behavioral assessments within 48-120 hours of symptom onset
• Unable to receive TMS or get MRI within 72-168 hours of symptom onset
• Anticipated inability to perform study procedures within 168 hours of symptom onset.
Diagnostic Test: Transcranial Magnetic Stimulation (TMS)
The Placebo-Controlled Efficacy in Idiopathic Normal Pressure Hydrocephalus (iNPH) Shunting
(PENS) trial is a multi-center blinded, randomized, placebo-controlled design investigation
of cerebrospinal fluid (CSF) shunt surgery to study the shunt efficacy in iNPH patients.
1. Age ≥ 60 years; and
2. Diagnosis of iNPH and recommendation for shunt surgery based on the Investigator's
clinical judgement based on criteria and testing as described in the iNPH Guidelines;
3. Evans Ratio ≥ 0.30; and
4. One positive supplementary test to include either large volume Lumbar Puncture or
extended CSF drainage per institutional standards; and
5. History or evidence of gait impairment (such as decreased step height or length,
decreased speed, retropulsion as described in the iNPH Guidelines) duration ≥ 6
months; and
6. Participant has the sensory motor skills, communication skills and understanding to
comply with the testing and reporting required in the PENS trial; and
7. Participant is able to give written informed consent.
Exclusion Criteria:
1. Unable to walk 10 meters with or without an assistive device; or
2. Baseline fastest gait velocity (out of three gait trials) >1 m/sec prior to drainage
trial and fastest gait velocity improvement is < 30% with or without an assistive
device; or
3. Unable to return to the study center for follow up evaluation and shunt programming;
or
4. Participant is not medically cleared for shunt surgery per local standards; or
5. Secondary NPH. (Prior encephalitis, meningitis, subarachnoid hemorrhage, traumatic
brain injury (including concussion) within two years or with brain injury or skull
fracture on baseline imaging, brain abscess, brain tumor, obstructive hydrocephalus
(including acquired aqueductal stenosis and carcinomatous meningitis); or
6. Prior or existing shunts, endoscopic third ventriculostomy, or any previous surgical
intervention for hydrocephalus; or
7. Previous intracranial neurosurgical procedure; or
8. Symptomatic cerebral or cerebellar infarction occurring within 6 months from screening
(asymptomatic lacunar infarctions are permitted); or
9. Diagnosis of Parkinsonian syndrome that, in the investigator's judgment, will
complicate the outcome evaluation; or
10. Diagnosis of schizophrenia or any psychiatric diagnosis (including depression) that,
in the investigator's judgment, will complicate the outcome evaluation (such as
neuroleptic treatment for schizophrenia); or
11. Diagnosis of dementia disorder where the investigator considers cognition deficit
limits participation in the study; or
12. Conditions impairing gait that are considered to be unrelated to hydrocephalus, such
as hemiparesis, spasticity, cerebellar ataxia or musculoskeletal and joint disease,
which will interfere with gait assessment or the potential for gait improvement.
13. Individuals with contraindication to MRI (e.g., implanted electric and electronic
devices, aneurysm clip(s), any metallic fragment or foreign body, coronary and
peripheral artery stents, cardiac pacemaker, known claustrophobia, or known/possible
pregnancy or breast-feeding) will be excluded according to institutional guidelines.
Environmental Epidemiology of Essential Tremor (RULET)
This study's research is devoted to studying the causes of tremor, and especially essential
tremor (ET), which is the most common type of tremor. Previous studies have revealed a link
between harmane [HA], a dietary neurotoxin, and ET; these studies now also suggest a link
between this toxin and Parkinson's disease (PD), a related tremor disorder. Yet these links
are tentative rather than conclusively established; therefore, in this new patient-based
proposal, which incorporates investigations spanning two continents (North America and
Europe), utilizes several complementary study designs (prospective cohort, case control), and
draws on several types of tissue (blood, brain), our goal is to nail down the links between
HA and ET and to further solidify the emerging links between HA and PD.
• Essential Tremor
• Subjects must be 50 years of age or older.
• Subjects must have been diagnosed with Essential Tremor
• Subjects must live within 3 hours of UTSW
• Parkinson's Disease
• Subjects must be 50 years of age or older.
• Subjects must have been diagnosed with Parkinson's Disease
• Subjects must live within 3 hours of UTSW
• Healthy Individuals
• Healthy individuals living within 3 hours of UTSW
• Subjects must be 50 years of age or older
• You are healthy and have not being diagnosed with any neurological disease
• Essential Tremor and Parkinson's Disease
• Subjects must be 50 years of age or older.
• Subjects must have been diagnosed with Essential Tremor
• Subjects must have been diagnosed with Parkinson's Disease preceded by at least 3
years of enrollment in study
• Subjects must live within 3 hours of UTSW
Exclusion Criteria:
• Healthy Individuals
• Subjects with medical history of neurological conditions
• Subjects with family history of neurological condition
• Subjects with spouse diagnosed with Essential Tremor or Parkinson's Disease
• Essential Tremor
• Subjects with medical history of another movement disorder such as Parkinson's
Disease or dystonia
• Subjects with head tremor that preceded hand tremor
• Parkinson's Disease
--Subjects with medical history of Essential Tremor
• Essential Tremor and Parkinson's Disease
• Criteria that does not meet inclusion
Parkinson Disease, Essential Tremor, Brain and Nervous System
Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy (DEVOTE)
The primary objectives of this study are to examine the clinical efficacy of nusinersen
administered intrathecally at higher doses to participants with spinal muscular atrophy
(SMA), as measured by change in Children's Hospital of Philadelphia-Infant Test of
Neuromuscular Disorders (CHOP-INTEND) total score (Part B); to examine the safety and
tolerability of nusinersen administered intrathecally at higher doses to participants with
SMA (Parts A and C).
The secondary objectives of this study are to examine the clinical efficacy of nusinersen
administered intrathecally at higher doses to participants with SMA (Parts A, B and C); to
examine the effect of nusinersen administered intrathecally at higher doses to participants
with SMA (Parts A and C); to examine the safety and tolerability of nusinersen administered
intrathecally at higher doses to participants with SMA, to examine the effect of nusinersen
administered intrathecally at higher doses compared to the currently approved dose in
participants with SMA (Part B).
Part A, B and C:
•Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound
heterozygote)
Part A:
• Onset of clinical signs and symptoms consistent with SMA at > 6 months (> 180 days) of
age (i.e., later-onset SMA)
• Age 2 to ≤ 15 years, inclusive, at the time of informed consent
Part B:
• Participants with SMA symptom onset ≤ 6 months (≤ 180 days) of age (infantile onset)
should have age > 1 week to ≤ 7 months (≤ 210 days) at the time of informed consent
• Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):
• Age 2 to < 10 years at the time of informed consent
• Can sit independently but has never had the ability to walk independently
• HFMSE score ≥ 10 and ≤ 54 at Screening
Part C:
•Currently on nusinersen treatment at the time of Screening, with the first dose being at
least 1 year prior to Screening
Part C Cohort 1:
•Participants of any age (individuals ≥18 years of age at Screening must be ambulatory)
Part C Cohort 2:
• Participants ≥18 years of age at Screening (can be ambulatory or nonambulatory)
• HFMSE total score ≥4 points at Screening
• RULM entry item A score ≥3 points at Screening
Key
Exclusion Criteria:
Part A, B and C:
• Presence of an untreated or inadequately treated active infection requiring systemic
antiviral or antimicrobial therapy at any time during the Screening period
• Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or of an
implanted central nervous system (CNS) catheter
• Hospitalization for surgery, pulmonary event, or nutritional support within 2 months
prior to Screening or planned within 12 months after the participant's first dose
Part A:
• Respiratory insufficiency, defined by the medical necessity for invasive or
noninvasive ventilation for > 6 hours during a 24-hour period, at Screening
• Medical necessity for a gastric feeding tube
• Treatment with an investigational drug given for the treatment of SMA, biological
agent, or device within 30 days or 5 half-lives of the agent, whichever is longer,
prior to Screening or anytime during the study; any prior or current treatment with
any survival motor neuron-2 gene (SMN2)-splicing modifier or gene therapy; or prior
antisense oligonucleotide treatment, or cell transplantation
Part B:
• Treatment with an investigational drug including but not limited to the treatment of
SMA, biological agent, or device within 30 days or 5 half-lives of the agent,
whichever is longer, prior to Screening or anytime during the study; any prior or
current treatment with any SMN2-splicing modifier or gene therapy; or prior antisense
oligonucleotide treatment, or cell transplantation
• Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):
• Respiratory insufficiency, defined by the medical necessity for invasive or
noninvasive ventilation for > 6 hours during a 24-hour period, at Screening
• Medical necessity for a gastric feeding tube
• Participants with SMA symptom onset ≤ 6 months (≤ 180 days) of age (infantile onset):
Signs or symptoms of SMA present at birth or within the first week after birth
Part C:
• Concurrent or previous participation and/or administration of nusinersen in another
clinical study
• Concomitant or previous administration of any SMN2-splicing modifier (excluding
nusinersen) or gene therapy, either in a clinical study or as part of medical care.
• Concurrent or previous participation in any interventional investigational study for
any other drug or device within 30 days or 5 half-lives of the agent, whichever is
longer, prior to Screening
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia
The 2020 NIMH Strategic Plan for Research calls for investigations targeting neurobiology of
mental illness across the lifespan. Growing evidence suggests that lifespan neurobiology of
schizophrenia (SZ) incorporates two distinct dimensions: aging and disease course. However,
their clinical correlates, associated biomarker trajectories, and implications for treatment
are unknown. This study will investigate differential aspects of SZ neurobiology captured by
aging and disease course, in order to develop specific biomarkers which may offer actionable
targets for SZ stage-dependent intervention. The study is predicated on a novel mechanistic
Model of SZ Trajectories across the Adult Lifespan, positing distinct biological fingerprints
within the anterior limbic system for aging and disease course in SZ: (1) alterations in the
circuit's function and structure that occur earlier in the lifespan and are larger in
magnitude than the alterations expected with normal aging (accelerated aging dimension); and
(2) regionally-specific anterior limbic "hyperactivity" in early SZ, with a subsequent
transformation into "hypoactivity" in advanced SZ (disease course dimension). In a sample of
SZ and matched healthy controls (n=168, 84/group) aged 18-75 years the investigators will
ascertain a broad panel of biomarkers [via multimodal brain imaging: optimized 1H-MRS,
high-resolution task-based fMRI, perfusion (Vascular Space Occupancy) and structural MRI],
along with comprehensive cognitive and clinical assessments. All measures will be acquired at
baseline and repeated at 2-year longitudinal follow-up. Using cutting-edge computational
approaches, the study will examine (i) effects of aging and SZ course on anterior limbic
system biomarkers; (ii) lifespan trajectories for different biomarkers; (iii) patterns of
limbic system biomarkers in age- and SZ course-based subgroups (e.g., Younger vs. Older,
Early-Course vs. Advanced SZ), as well as in data-driven subgroups (e.g., those with vs.
without accelerated aging profiles); and (iv) associations between biomarkers and cognitive
and clinical outcomes. This research will advance the field by providing novel biomarkers
that capture unique neurobiological contributions of aging and disease course in SZ, and will
motivate future studies on SZ mechanisms across the lifespan and development of precision
treatments.
• 18-65 years of age (SZ); 18-75 years of age (CON)
• Women and men
• All races and ethnicities
• Psychiatric diagnoses:
Patient participants (SZ): Meet DSM-5 criteria for schizophrenia or schizoaffective
disorder Healthy control participants (CON): No personal history of lifetime psychiatric
disorders, or a family history of psychotic disorders in 1st-or 2nd- degree relatives
• Able to read, speak, and understand English
• Able and willing to provide written informed consent; and willing to commit to the
study protocol, including 2-year longitudinal follow-up
Exclusion Criteria:
• Compromised cognitive function: Both SZ and CON participants: Estimated premorbid
intellectual ability <75 age-corrected score on Wide Range Achievement Test-4/Word Reading
Subtest (WRAT-4) CON participants: <26 score on the Montreal Cognitive Assessment (MoCA)
• Neurological or medical disorder that may affect brain function (history of stroke,
head injury with a loss of consciousness >10 min, seizure disorder, AIDS, poorly
controlled hypertension, poorly controlled diabetes, decompensated lung disease, etc.)
• Co-morbid DSM-5 diagnosis of drug/alcohol use disorder in prior 3 months
• Current treatment with benzodiazepine or non-benzodiazepine sedatives/hypnotics,
and/or anticonvulsants
• Presence of ferromagnetic objects in body
• Weight or body size exceeding MRI scanner capacity [>300 lbs]
• Claustrophobia in MRI scanner
• Pregnant women
• Breastfeeding women (VASO scan will not be administered. All other imaging modalities
are safe to administer.)
• Impaired kidney function: Glomerular Filtration Rate (GFR) < 30 ml/min/1.73m2 (VASO
scan will not be administered due to an association between Gadolinium-based MR
contrast use and Nephrogenic Systemic Fibrosis in individuals with severely impaired
renal function. All other imaging modalities are safe to administer.)
• History of hypersensitivity to any MRI contrast agent (VASO scan will not be
administered. All other imaging modalities are safe to administer.)
Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers
Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the
valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein.
Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac
amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and
premature death. Fortunately, new therapies that stabilize TTR improve morbidity and
mortality in hATTR-CA, especially when prescribed early in the disease. However, hATTR-CA is
often diagnosed at an advanced stage and conventional diagnostic tools lack diagnostic
specificity to detect early disease.
The overall objectives of this study are to determine the presence of subclinical hATTR-CA
and to identify biomarkers that indicate amyloid progression in V122I TTR carriers. The
central hypothesis of this proposal is that hATTR-CA has a long latency period that will be
detected through subclinical amyloidosis imaging and biomarker phenotyping.
The central hypothesis will be tested by pursuing 2 specific aims: Aim 1) determine the
association of V122I TTR carrier status with CMRI evidence of amyloid infiltration; Sub-aim
1) determine the association of V122I TTR carrier status with cardiac reserve; Aim 2)
determine the association between amyloid-specific biomarkers and V122I TTR carrier status;
and Sub-aim 2) determine the association of amyloid-specific biomarkers with imaging-based
parameters and evaluate their diagnostic utility for identifying subclinical hATTR-CA. In Aim
1, CMRI will be used to compare metrics associated with cardiac amyloid infiltration between
a cohort of V122I TTR carriers without HF formed by cascade genetic testing and age-, sex-,
and race-matched non-carrier controls. For Sub-Aim 1, a sub-sample of carriers and
non-carrier controls enrolled in Aim 1 will undergo novel exercise CMRI to measure and
compare cardiac systolic and diastolic reserve. Aim 2 involves measuring and comparing
amyloid-specific biomarkers in V122I TTR carriers without HF with samples matched
non-carriers (both from Aim 1) and individuals with symptomatic V122I hATTR-CA from our
clinical sites. These biomarkers detect and quantify different processes of TTR
amyloidogenesis and include circulating TTR, retinol binding protein 4, TTR kinetic
stability, and misfolded TTR oligomers. Sub-aim 2 will establish the role of these biomarkers
to detect imaging evidence of subclinical hATTR-CA disease.
• Men and women ages 30-80 who are V122I TTR carriers (or matched non-carriers) without
history of HF (this will be assessed by study personnel) and defined as: a) No history
of hospitalization within the previous 12 months for management of HF; b) Without an
elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within
the previous 12 months; or c) No clinical diagnosis of HF from a treating clinician
• Signed informed consent
Exclusion Criteria:
• A self-reported history or clinical history of HF
• Other known causes of cardiomyopathy
• History of light-chain cardiac amyloidosis
• Prior type 1 myocardial infarction (non-ST segment elevation myocardial Infarction
{NSTEMI} or ST-elevation myocardial infarction {STEMI})
• Cardiac transplantation
• Body weight >250 lbs
• Estimated glomerular filtration rate ≤30 mL/min/1.73 m2
• Inability to safely undergo CMRI
(For participants with symptomatic V122I hATTR-CA, we will enroll probands with HF from Aim
1 or patients with symptomatic V122I hATTR-CA from the three study sites.)
Inclusion Criteria:
• Men and women ages 30-80 who have symptomatic V122I hATTR-CA as determined by a
history of HF (this will be assessed by study personnel) and defined as: a) History of
hospitalization within the previous 12 months for management of HF; b) An elevated
B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the
previous 12 months; or c) A clinical diagnosis of HF from a treating clinician.
• Have an established diagnosis of hATTR-CA based on either a) Biopsy confirmed by Congo
red (or equivalent) staining with tissue typing with immunohistochemistry or mass
spectrometric analysis or immunoelectron microscopy, OR b) positive technetium-99m
(99mTc)-pyrophosphate or -bisphosphonate scan, combined with accepted laboratory
criteria without abnormal M-protein.
• TTR gene sequencing confirming the V122I variant
• Signed informed consent
Exclusion Criteria:
• Other known causes of cardiomyopathy
• History of light-chain cardiac amyloidosis
• Cardiac transplantation
• Liver transplantation
• Previous Treatment with a TTR stabilizer (tafamidis, acoramidis) or TTR silencer
(inotersen, patisiran, eplontersen)
• Estimated glomerular filtration rate ≤30 mL/min/1.73 m2
The goal of this study is to is to focus on the genetic influences on Alzheimer's Disease
(AD) risk. The investigators are looking for families and/or individuals (affected or
unaffected) of any ethic background (African American, Caucasian, and Hispanics) with a
family history of AD and willing to participate.
• Established diagnosis of definite or probable AD or have a diagnosis of a related
neurodegenerative disorder such as Frontotemporal Dementia (FTD) or Lewy Body Dementia
(LBD) (will also recruit sporadic FTD and LBD) cases.
• a living sibling with probable or possible AD;
• a third living relative affected with AD (onset age 50 or older) or unaffected (60 or
older);
• participants in the proband's generation with an identified companion serving as an
informant;
• participants who have capacity to consent or participants lacking capacity to consent
with a surrogate/proxy in place to provide consent.
Exclusion Criteria:
• failure to identify an appropriate informant;
• uncertainty of the clinical diagnosis of Alzheimer's disease or other related
disorder;
• discovery of additional diagnosis that could account for the clinical manifestations;
• unwillingness to participate;
• failure to identify a living sibling with AD or other related disorder (except in the
cases of sporadic FTD and sporadic LBD);
• participants lacking the capacity to consent who do not have a surrogate or proxy or
next of kin to provide consent.
Genetic: Blood Draw, Other: Late Onset Alzheimer's Disease (LOAD) Neuropsychological Battery Test