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Prospective Clinical Assessment Study in Children With Achondroplasia (ACH)
This is a long-term, multi-center, observational study in children 2.5 to 10 years with achondroplasia (ACH). The objective is to evaluate growth, ACH-related medical complications and treatments of study participants. No study medication will be administered.
30 Months to 10 Years old
• Signed informed consent by study participant or parent(s) or legally authorized representative (LAR) and signed informed assent by the study participant (when applicable)
• Aged 2.5 to 10 years (inclusive) at study entry
• Diagnosis of ACH
• Ambulatory and able to stand without assistance
• Study participants and parent(s) or LAR(s) are willing and able to comply with study visits and study procedures
• Have hypochondroplasia or short stature condition other than ACH (e.g trisomy 21, pseudoachondroplasia, psychosocial short stature)
• In females, having had their menarche
• Height < -2 or > +2 standard deviations for age and sex based on reference tables on growth in children with ACH
• Annualized height growth velocity ≤1.5 cm/year over a period ≥6 months prior to screening
• Have a concurrent disease or condition that in the view of the Investigator and/or Sponsor, may impact growth or where the treatment is known to impact growth.
• Significant abnormality in screening laboratory results.
• Have been treated with growth hormone, insulin-like growth factor 1 (IGF 1), or anabolic steroids in the previous 6 months or long-term treatment (>3 months) at any time
• Have received a C-type natriuretic peptide (CNP) analog or treatment targeting fibroblast growth factor receptor (FGFR) inhibition at any time
• Have had regular long-term treatment (>1 month) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable)
• Have used any other investigational product or investigational medical device for the treatment of ACH or short stature
• Have had previous limb-lengthening surgery
Skeletal dysplasia, Endochondral ossification, ACH, Shortened proximal limbs, Fibroblast growth factor receptor 3, FGFR3, Endochondral bone formation, Short-limb disproportionate dwarfism, Bone disease, Dwarfism, Bone diseases, Musculoskeletal diseases, Osteochondrodysplasia, Genetic diseases, Inborn
Parkland Health & Hospital System
Natural History Study of SCID Disorders
This study is a prospective evaluation of children with Severe Combined Immune Deficiency (SCID) who are treated under a variety of protocols used by participating institutions. In order to determine the patient, recipient and transplant-related variables that are most important in determining outcome, study investigators will uniformly collect pre-, post- and peri-transplant (or other treatment) information on all children enrolled into this study. Children will be divided into three strata: - Stratum A: Typical SCID with virtual absence of autologous T cells and poor T cell function - Stratum B: Atypical SCID (leaky SCID, Omenn syndrome and reticular dysgenesis with limited T cell diversity or number and reduced function), and - Stratum C: ADA deficient SCID and XSCID patients receiving alternative therapy including PEG-ADA ERT or gene therapy. Each Group/Cohort Stratum will be analyzed separately.
Inclusion Criteria:Stratum A: Typical SCID (formerly referred to as Classic SCID)- -Subjects who meet the following inclusion criteria and the intention is to treat with allogeneic hematopoietic cell transplant (HCT) are eligible for enrollment into Stratum A (Typical SCID) of the study:
• Absence or very low number of T cells (CD3 T cells <300/microliter) AND
• No or very low T cell function (<10% of lower limit of normal) as measured by response to phytohemagglutinin (PHA) OR
• T cells of maternal origin present. Stratum B: Leaky SCID, Omenn Syndrome, Reticular Dysgenesis- -Subjects who meet the following criteria and the intention is to treat with HCT are eligible for enrollment into Stratum B: Leaky SCID:
• Maternal lymphocytes tested for and not detected AND
• Either one or both of the following (a,b) :
• a.) <50% of lower limit of normal T cell function as measured by response to PHA, OR response to anti-CD3/CD28 antibody
• b.) Absent or <30% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens
• AND at least two of the following (a through e):
• a.) Reduced number of CD3 T cells
• age ≤2 years: <1500/microliter
• age >2 years and ≤4 years: <800/microliter
• age >4 years: <600/microliter
• b.) ≥80% of CD3+ or CD4+ T cells that are CD45RO+
• AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative
• AND/OR >50% of CD3+ or CD4+T cells express HLA-DR (at <4 years of age)
• AND/OR are oligoclonal T cells
• c.) Hypomorphic mutation in IL2RG in a male, or homozygous hypomorphic mutation or compound heterozygosity with ≥1 hypomorphic mutation in an autosomal SCID-causing gene
• d.) Low T Cell Receptor Excision Circles (TRECs) and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal.
• e.) Functional testing in vitro supporting impaired, but not absent, activity of the mutant protein, AND
• Does not meet criteria for Omenn Syndrome. Omenn Syndrome:
• Generalized skin rash
• Maternal lymphocytes tested for and not detected; --Note: If maternal engraftment was not assessed and ruled out, the subject is not eligible as Omenn Syndrome.
• ≥80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR
• 80% of CD3+ or CD4+T cells are CD62L negative AND/OR
• 50% of CD3+ or CD4+ T cells express HLA-DR (at <2 years of age);
• Absent or low (< 30% lower limit of normal) T cell proliferation response to antigens (Candida, tetanus) to which the subject has been exposed NOTE: If proliferation to antigen was not performed, but at least 4 of the following 9 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the subject is eligible as Omenn Syndrome:
• Elevated IgE
• Elevated absolute eosinophil count
• *Oligoclonal T cells measured by CDR3 length or flow cytometry
• *Proliferation to PHA is reduced <50% of lower limit of normal or SI <30
• *Hypomorphic mutation in a SCID causing gene
• Low TRECS and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal. Reticular Dysgenesis:
• Absence or very low number of T cells (CD3 <300/µL
• No or very low (<10% lower limit of normal) T cell response to PHA
• Severe neutropenia (absolute neutrophil count < 200 /µL) AND
• ≥2 of the following (a,b,c):
• a.) Sensori-neural deafness
• b.) Deficiency of marrow granulopoiesis on bone marrow examination
• c.) A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified. Stratum C: Subjects who meet the following criteria and the intention is to treat with therapy other than allogeneic HCT, primarily PEG-ADA ERT or gene therapy with autologous modified (gene transduced) cells, are eligible for enrollment into Stratum C:
• ADA Deficient SCID with intention to treat with PEG-ADA ERT
• ADA Deficient SCID with intention to treat with gene therapy
• X-linked SCID with intention to treat with gene therapy
• Any SCID patient previously treated with a thymus transplant (includes intention to treat with HCT, as well as PEG-ADA ERT or gene therapy)
• Any SCID patient who received therapy for SCID deemed "non-standard" or "investigational", including in utero procedures.
Exclusion Criteria:-Subjects who meet any of the following exclusion criteria are disqualified from enrollment in Strata A, B, or C of the study:
• Presence of an Human Immunodeficiency Virus (HIV) infection (by PCR) or other cause of secondary immunodeficiency
• Presence of DiGeorge syndrome
• MHC Class I and MHC Class II antigen deficiency, and
• Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency or transcobalamin deficiency.
XSCID, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis, Severe Combined Immunodeficiency (SCID), ADA SCID, Unknown Sites
Severe Combined Immunodeficiency (SCID), natural history study, SCID treatment
Parkland Health & Hospital System
Does Caudal Block Increase the Incidence of Urethrocutaneous Fistula Formation Following Hypospadias Repair in Infants?
This is a prospective randomized multi-center non-inferiority trial conducted through the Pediatric Regional Anesthesia Network study sites to determine if caudal block increases the incidence of urethrocutaneous fistula following distal or mid shaft hypospadias repair compared with penile nerve block.
4 Months to 2 Years old
• infants/ children with midshaft or distal hypospadias undergoing primary single stage repair in one of the Pediatric Regional Anesthesia Network participating centers.
• prior hypospadias surgery,
• proximal or penoscrotal hypospadias,
• abnormal caudal anatomy or spinal dysraphism,
• cyanotic congenital heart disease,
• infection or rash at the block injection site.
Drug: Caudal block with ropivacaine, Drug: penile nerve block with bupivacaine
Hypospadias, Urethrocutaneous Fistula
hypospadias, caudal, urethrocutaneous fistula, penile nerve block
Parkland Health & Hospital System
Phase 3 Alogliptin Pediatric Study
The primary purpose of this study is to evaluate the efficacy of alogliptin 25 milligram (mg) once daily compared to placebo when administered as monotherapy, or when added onto a background of metformin alone, insulin alone, or a combination of metformin and insulin, as measured by the glycosylated hemoglobin (HbA1c) change from Baseline at Week 26 in pediatric participants with type 2 diabetes mellitus (T2DM).
10 Years to 17 Years old
Inclusion Criteria:1. Has a confirmed diagnosis of T2DM using American Diabetes Association (ADA) and World Health Organization (WHO) criteria (laboratory determinations of fasting plasma glucose [FPG] greater than or equal to [>=] 126 mg/dL, random glucose >=200 mg/dL [>=11.10 mmol/L], HbA1c >=6.5 percent (%), or 2-hour oral glucose tolerance test [OGTT] glucose >=200 mg/dL), documented in the participants' medical record. 2. The participant and/or his/her legal representative (that is, parents or legal guardians) are able and willing to monitor their own blood glucose concentrations with a home glucose monitor and complete participant diaries.
Exclusion Criteria:1. Has a history of hypersensitivity or allergy to alogliptin, other dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, insulin or related compounds. 2. Has a confirmed diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young (MODY). 3. Has a hemoglobin level <11.0 gram per deciliter (g/dL) (<110 gram per liter [g/L]) for males and <10.0 g/dL (<100 g/L) for females. 4. Has a history of any hemoglobinopathy that may affect determination of HbA1c levels. 5. Has a history of bariatric surgery. 6. Has a history of proliferative diabetic retinopathy within the 6 months prior to Screening. 7. Has had more than 1 episode of diabetic ketoacidosis (DKA) at any time after diagnosis of T2DM. 8. Has a history of more than 1 episode of pancreatitis. 9. Has serum creatinine >=1.5 mg/dL for male participants or >=1.4 mg/dL for female participants, or creatinine clearance <60 milliliter per minute (mL/min) based on calculation by central lab using the Schwartz formula for estimated glomerular filtration rate (eGFR) at screening Visit. 10. Has a documented history of infection with human immunodeficiency virus or chronic active viral hepatitis. 11. The participant and/or his/her legal representative (that is, parents or legal guardians) is unable to understand verbal or written English, or any other language for which a certified translation of the approved informed consent/assent is available. Additional Criteria That Must be Met Prior to Randomization: For participants who have had the diagnosis of T2DM for less than 1 year and/or who are taking insulin at Screening, additional criteria will need to be met prior to randomization: 1. Must have an HbA1c level of >=6.5% to <11.0% if the participant is treatment naïve or on metformin alone or >=7.0% to <11.0% if the participant is on insulin alone or in combination with metformin. 2. The participant must not have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to randomization. 3. Must not have received an antidiabetic agent other than metformin or insulin within the 12 weeks prior to randomization. 4. Must not have received oral or parenteral steroids for more than 3 weeks (cumulatively) within the 6 months prior to randomization or have received a course of oral or parenteral steroids within the 2 months prior to randomization. 5. Has a systolic blood pressure <160 millimeter of mercury (mmHg) and a diastolic pressure <100 mm Hg. (Antihypertensive medications will be allowed during the study). 6. Has an alanine aminotransferase (ALT) level <3*upper limit of normal (ULN) or an ALT level <5 *ULN with a confirmed diagnosis of nonalcoholic fatty liver disease (NAFLD).7. Does not plan to leave the geographic area within 1 calendar year following randomization. For participants who have had the diagnosis of T2DM for less than 1 year and/or who are taking insulin prior to randomization, the following criteria must also be met: 8. Must have a fasting C-peptide concentration>=0.6 nanogram per milliliter (ng/mL) (>=0.20 nanomole per liter [nmol/L]) (drawn at least 1 week after treatment for ketosis or acidosis, if applicable). 9. No presence of autoantibodies as documented by glutamic acid decarboxylase [GAD] 65 and islet antigen [IA]-2 antibodies below the upper limit of the normal reference ranges at randomization. 10. Have a body mass index (BMI) greater than (>) 85th percentile, documented at randomization.
Drug: Alogliptin Benzoate, Drug: Placebo
Diabetes Mellitus, Type 2
Parkland Health & Hospital System
Multicenter Prospective Cohort Study on Current Treatments of Legg-Calvé-Perthes Disease (IPSG1)
Legg-Calvé-Perthes disease is a childhood hip disorder which is common enough to be a significant public health problem (affects 1 in 740 boys between ages 0—14), but uncommon enough to have a sufficient number of patients from a single institution to perform a definitive prospective study comparing the results of current treatments. The present study will establish a database of prospectively identified patients with Legg-Calvé-Perthes (LCP) Disease and collect information regarding their presentation, treatment, and outcomes in the course of receiving currently available treatments. This study seeks to compare the outcomes of current treatments in the management of different age groups (ages 1-6, 6—8, 8—11, >11) of patients with Perthes disease at two- and five-year followup and at skeletal maturity. For each age group, two to three common treatment regimens currently used by practicing pediatric orthopaedic surgeons will be compared. The intervention a patient receives is determined through physician preference. Physicians pick an intervention for each age group and treat each patient with the same intervention.
6 Years to 16 Years old
• Diagnosed with Legg-Calvé-Perthes disease
• Between age 1-18
• Patients with possible secondary femoral osteonecrosis if over the age of 11 due to trauma or corticosteroid therapy are also eligible.
• Patients with previous surgical treatment on the affected hip if not in the >11 age group
Procedure: osteotomy, Procedure: multiple epiphyseal drilling
Legg Calve Perthes Disease, Bones and Joints
femur head necrosis, hip, pediatric orthopedics, MRI, Osteonecrosis, Bone diseases, Legg Calve Perthes Syndrome
G551D Observational Study- Expanded to Additional Genotypes and Extended for Long Therm Follow up (GOAL-e2) (GOAL- e2)
The goal of this research study is to collect blood and urine samples from people who have either the R117H type of CF or the non-G551D gating type of CF to be kept for future research.We will also use some of the collected blood to measure the number of neutrophils.
6 Years and over
Inclusion Criteria for Core Study: 1. Male or female ≥ 6 years of age at Visit 1. : 2. Must have a clinical diagnosis of cystic fibrosis and the following CFTR mutations: 1. For Cohort 1 (Closed to enrollment June 30, 2012): G551D on at least 1 allele Any known or unknown mutations allowed on second allele. 2. For Cohort 2: R117H on at least 1 allele Any known or unknown mutation on the second allele except G551D 3. For Cohort 3: A Non-G551D gating mutation on one allele: (G178R, S549N, S549R, G551S,G970R, G1244E, S1251N, S1255P, G1349D) Any known or unknown mutation on the second allele except G551D OR R117H 3. Enrolled in the Cystic Fibrosis Foundation Patient Registry (with the exception of Canadian sites). (Patients may enroll in the Registry at Visit 1 if not previously enrolled.) 4. Clinically stable with no significant changes in health status within the 14 days prior to Visit 1. 5. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative. Exclusion Criteria for Core Study 1. Participation in the VX-770-105, VX-770-106, VX-770-108, VX-770-110, VX-770-111, VX-770-112, or VX-770-113 study, VX-770 Extended Access Program or use of ivacaftor within 6 months prior to Visit 1. 2. Any upper or lower respiratory symptoms requiring treatment with oral, inhaled or IV antibiotics within the 2 weeks prior to Visit 1. 3. History of solid organ transplantation. 4. Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the patient or the quality of the data.
Cystic Fibrosis, G551D, G551D Mutation
UT Southwestern; Parkland Health & Hospital System
Healthy Sleep for Children With Down Syndrome (HELP-DS)
The purpose of this multi-center observational study (utilizing the sites enrolling patients for the Pediatric Adenotonsillectomy Trial for Snoring (PATS) [1U011HL125307-O1A1]) is to gather data regarding children with Down syndrome (DS) and Sleep Disordered Breathing (SDB) referred for treatment with adenotonsillectomy to inform a future randomized controlled trial in this population.
3 Years to 13 Years old
• DS diagnosis regardless of genetic status (e.g., mosaicism or translocation).
• Aged >3 to <13 years at the date of consent.
• Primary indication for AT is nocturnal obstructive symptoms (i.e., not recurrent infections or other indications).
• Deemed to be a candidate for AT by Ear, Nose and Throat (ENT) evaluation; that is, no technical issues that would be a contraindication for surgery such as submucous cleft palate.
• Prior tonsillectomy (partial or complete).
• Severe chronic health conditions that would contradict surgery (severe morbid obesity, unrepaired cyanotic congenital heart disease, bleeding disorders).
• Severe behavioral problems that would preclude participation in the study's testing procedures (PSG, actigraphy).
• Severe OSA with respiratory failure needing urgent/emergent management
• Plan to undergo additional airway surgery at the time of AT.
• Caregiver/child planning to move out of the area within 6 months.
• Caregiver/child does not speak English or Spanish well enough to complete the behavioral and performance measures.
• Child in foster care.
Down Syndrome, Sleep Disordered Breathing
Parkland Health & Hospital System
Red Blood Cell Exchange Transfusion as a Novel Treatment for GLUT1 Deficiency Syndrome
This proposal is an investigator-initiated, single-site proof of concept trial. Five patients will undergo isovolemic hemodilution-red cell exchange (IHD- RBCx) with up to 10 units of red cell antigens (Rh group, Kell, Duffy, Kidd blood group antigens) matched normal donor red cells to replace a target of 70% of the patient's red cells with donor red cells. The procedure will be performed as an outpatient according to protocols established for sickle cell anemia patients. One of the investigators is an expert on RBCx and will oversee the transfusion. Subjects will be assessed before and after transfusion, and at two months post transfusion. Outcome measures include neurological exam, electroencephalography (EEG), neuropsychological testing, and biochemical assays.
16 Years to 64 Years old
Early Phase 1
• Male or Female
• Age 16 years to 64 years old.
• Diagnosed with genetically-confirmed glucose transporter type 1 disorder
• Patients not currently receiving dietary therapy, including ketogenic diet or other dietary therapy, due to failure of these diets to achieve seizure remission or due to patient preference, including compliance or tolerance issues. Patients currently on Modified Atkins Diet (MAD) and / or taking Medium Chain Triglyceride (MCT) oil are allowed.
• Currently on the ketogenic diet or taking triheptanoin (C7) oil
• No genetic confirmation of G1D diagnosis
• Unable to return for follow up visits
• Weak peripheral veins, such that IV placement is contraindicated (required for transfusion)
• Serious chronic medical conditions, such as congestive heart failure, renal failure, liver failure, or any other medical conditions that preclude large volume transfusions.
• Patients currently pregnant or breast-feeding are excluded from participating in this research. Patients who plan on getting pregnant during this research or who are unwilling to use birth control, including abstinence, during the course of this research are also excluded due to safety concerns for the fetus.
Other: Red Blood Cell Transfusion
Glucose Transporter Type 1 Deficiency Syndrome, GLUT1DS1, Brain and Nervous System, Other Hematopoietic
G1D, Glucose transporter
UT Southwestern; Parkland Health & Hospital System
Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science (DHREAMS)
The goal of this study is to identify genes that convey susceptibility to congenital diaphragmatic hernia in humans. The identification of such genes, and examination of their structure and function, will enable a delineation of molecular pathogenesis and, ultimately, prevention or treatment of congenital diaphragmatic hernia. There are many different possible modes of inheritance for congenital anomalies, including autosomal dominant, autosomal recessive, and multifactorial. Multi-factorial inheritance is responsible for many common medical disorders, including hypertension, myocardial infarction, diabetes and cancer. This type of inheritance pattern appears to involve environmental factors as well as a combination of genetic variations that together can predispose to or produce congenital anomalies, such as congenital diaphragmatic hernia. Our study is designed to establish a small, well-defined genetic resource consisting of 1) Nuclear families suitable for linkage analysis by parametric,non-parametric (e.g. sib pairs, TDT) and association techniques, 2) Individuals with congenital diaphragmatic hernia who can be directly screened for allelic variation in candidate genes, and 3) Individuals who can serve as controls (are unaffected by congenital diaphragmatic hernia). Neonates and their families will be collected from homogenous and heterogeneous populations. By characterizing diverse populations, it should be possible to increase the likelihood of demonstration of genetic variation in selected candidate genes that can then be used in association and linkage studies in individual subjects with congenital diaphragmatic hernia.
• All individuals affected with a congenital diaphragmatic hernia (CDH), or with a family history of a CDH
• Individuals with no personal history of a CDH or family history of a family member affected with congenital diaphragmatic hernia
Congenital Diaphragmatic Hernia
Congenital Diaphragmatic Hernia (CDH), Genes, Genetic, Genetic testing, exome sequencing, genome sequencing, RNAseq
UT Southwestern; Children’s Health; Parkland Health & Hospital System