Search Results Within Category "Heart and Vascular"
Efficacy and Safety of Mibavademab in Adult and Pediatric Patients With Generalized Lipodystrophy (LAGO)
This study is researching a new drug called mibavademab (called "study drug"). The study involves participants with a condition called Generalized Lipodystrophy (GLD). The aim of the study is to see how well mibavademab works and what side effects it has. Researchers will also look at how much mibavademab is in the body at different times. This is a 2-part study: Part A is an efficacy study in pediatric and adult participants, Part B is a safety and pharmacokinetic study in pediatric participants. The study is researching several other questions, including: * How mibavademab affects the amount of sugar in the blood * How mibavademab affects the amount of fat (triglycerides) in the blood * How mibavademab affects the amount of fat that has built up in the liver * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
studyfinder@utsouthwestern.edu
• Participants ≥2 years of age at screening
• At least one of the below criteria are fulfilled during screening (measurements can be repeated once during screening period) * HbA1c ≥7% * Fasting TG ≥500 mg/dL * Fasting TG value of ≥300 mg/dL and the presence of another complication of GLD consistent with leptin deficiency (history of diabetes mellitus, hyperphagia, Metabolic Associated Fatty Liver Disease (MAFLD), polycystic ovary syndrome, etc)
• Weight ≥15 kg at screening
• Willing and able to provide, or have the treating physician provide, values of HbA1c and fasting TG from at least 6 months prior to screening, as described in the protocol For Part B only:
• Participants \<12 years of age at screening
• Weighing ≥7 kg at screening
• No metabolic criteria for study entry is required, as described in the protocol Key
• Has a current diagnosis of familial or acquired partial lipodystrophy or autoimmune (Type 1) diabetes mellitus
• Any malignancy, eg, lymphoma, within the past 1 year, prior to screening visit, as described in the protocol
• eGFR of \<30 mL/min/1.73 m2 based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine or Schwartz equation, as applicable, at screening. Assessment can be repeated once
• History of heart failure hospitalization, diagnosis of a myocardial infarction, stroke, clinically significant arrhythmia, as described in the protocol
• Treatment with over-the-counter or prescription medications with the intention of weight loss within 3 months prior to the screening visit For Part A only:
• Treatment with metreleptin within 3 months of the screening visit
• Addition or discontinuation of prescription medications or over-the-counter supplements for diabetes and/or dyslipidemia within 3 months prior to the start of the screening period, or changes in the use of these medications, as described in the protocol
• Significant changes to lifestyle and diet, as described in the protocol
• Current chronic treatment with high-dose corticosteroids, defined as use of higher than physiologic doses, as described in the protocol NOTE: Other protocol defined inclusion/exclusion criteria apply.
A Safety, Tolerability, and Biomarker Trial of VS-041 in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF)
A Safety, Tolerability, and Biomarker Trial of VS-041 in Participants with Heart Failure with Preserved Ejection Fraction (HFpEF)
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Serrano@UTSouthwestern.edu
• Males or females ≥ 50 years of age at the time of signing the informed consent.
• Diagnosis of HFpEF as defined by European Society of Cardiology or American College of Cardiology/American Heart Association criteria
• NYHA Functional Class II or III
• LVEF ≥ 50% demonstrated by echocardiography (ECHO) performed at Screening with evidence of heart failure
• Elevated NT-proBNP at Screening
• NordicPRO-C6™ ≥ 11 ng/mL at Screening.
• Stable dose of all concomitant HF medications for at least 4 weeks prior to Screening.
• Body weight of at least 110 lbs (50 kg) and body mass index (BMI) within the range ≥ 18 to \< 45 kg/m2.
• Males must agree to the contraception requirements and females must be of non-childbearing potential
• Able to understand and willing to sign a written informed consent form (ICF).
• Willing and able to comply with trial procedures and restrictions listed in the ICF and in this protocol.
• Female trial participant who is pregnant or breastfeeding.
• Known hypersensitivity to VS-041.
• Cardiovascular disease other than HFpEF
• Active intercurrent illness such as acute bacterial or viral infection.
• History of illicit drug or alcohol abuse or addiction that in the opinion of the PI could affect participation.
• Active chronic viral infection such as Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) at Screening.
• Acute decompensated HF within 30 days of Screening
• Lung disease within 12 months prior to Screening
• History of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.
• History of any other condition including psychiatric disorders that, in the opinion of the PI, may preclude the participant from following and completing the protocol.
• Have participated within the last 6 months in a clinical study involving an investigational product.
• Any other reason which, in the opinion of the PI, would prevent the participant from participating in the trial.
CLEOPATTRA: A Research Study to Look at the Effects of Treatment With a Medicine Called Coramitug (NNC6019-0001) in People With Heart Failure Due to Transthyretin Amyloid (ATTR) Amyloidosis (CLEOPATTRA)
This study will find out if a new medicine called NNC6019-0001 can help reduce the risk of heart-related death and illness in participants with a condition called transthyretin amyloid cardiomyopathy (ATTR-CM), which affects the heart. Participants will either receive NNC6019-0001 or a placebo (a treatment with no active medicine), and which one they get is decided by chance. Everyone in the study will continue receiving their usual heart treatments as recommended by their doctor.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Therese.Vallina@UTSouthwestern.edu
• Male or female.
• Age 18 years or above at the time of signing the informed consent.
• Have an established diagnosis of ATTR-CM (wild-type ATTR \[ATTRwt\] or variant ATTR \[ATTRv\]), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF. Note: Target ATTRv recruitment is approximately 15 percent of the study population. a. Cardiac amyloid infiltration demonstrated by: i. Cardiac biopsy positive for TTR amyloid, OR ii. Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylene diphosphonate (HMDP) nuclear medicine imaging with single-photon emission computed tomography (SPECT) or SPECT/CT (preferably) combined with an extracardiac biopsy positive for TTR amyloid, OR iii. Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP nuclear medicine imaging with SPECT or SPECT/CT (preferably) combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE)/or mass spectrometry based methods including mass fixation). Notes: * Non-invasive diagnostic pathway will be confirmed by a centralised expert review. * Bone tracer nuclear medicine imaging with SPECT or SPECT/CT (preferably) will be conducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP). * The eGFR adjusted acceptable serum free light chain ratio. * Patients with Grade 2 or 3 cardiac uptake at PYP/DPD/HDMP nuclear imaging with SPECT or SPECT/CT (preferably) and evidence of monoclonal gammopathy of undetermined significance (MGUS; based on serum and urine protein electrophoresis and serum free light chains) will require endomyocardial biopsy with typing using mass spectrometry or immunohistochemistry to confirm presence of TTR protein in tissue. * Timing of serum free light chain ratio, SPIE, UPIE and mass spectrometry-based methods including mass fixation should be within 12 months of SPECT or SPECT/CT nuclear imaging. b. Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm). c. Chronic HF (New York Heart Association \[NYHA\] Class I-IV): i. At least 1 documented hospitalisation for HF, OR ii. History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on x-ray or auscultation, or peripheral oedema that required or requires ongoing treatment with a diuretic).
• Expected to be on stable cardiovascular medical therapy (defined as no greater than 50 percent dose adjustment and no categorical changes of medications), with the exception of diuretics, 4 weeks prior to the randomisation visit.
• Completed more than 50 meters on the 6MWT at screening.
• Known or suspected hypersensitivity to study intervention(s) or related products.
• Current or previous participation (dosing with active treatment) in a study for an investigational ATTR depleting drug or ATTR gene editing therapy.
• Total bilirubin greater than 3 times the upper limit of normal (ULN) at screening.
• Current diagnosis or history of amyloid light chain, other non-ATTR amyloidosis, known leptomeningeal amyloidosis, or multiple myeloma.
• HF not primarily caused by ATTR-CM (e.g., due to hypertension, valvular heart disease, or ischemic heart disease in the opinion of the investigator).
• Currently hospitalised or hospitalised within 14 days prior to screening.
• Currently treated with positive inotropic medication.
• Uncorrected, severe, haemodynamically significant, left-sided heart valve disease.
• Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularisation, cardiac device implantation, cardiac valve repair, or major surgery within 60 days of screening.
• Prior solid organ transplant or planned solid organ transplant during the study.
• Left ventricular ejection fraction (LVEF) less than 30 percent as assessed by centralised review of echocardiography.
• Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, carcinoma in situ/high-grade prostatic intraepithelial neoplasia \[PIN\], low-risk prostate cancer, or on stable therapy for prostate cancer) within 3 years before screening.
• End-stage renal disease (estimated glomerular filtration rate \[eGFR\] less than 15 mL/min/1.73 m\^2 at screening, or chronic/intermittent haemodialysis or peritoneal dialysis).
Assessing the Impact of Muvalaplin on Major Cardiovascular Events in Adults With Elevated Lipoprotein(a) (MOVE-Lp(a))
The purpose of this study is to evaluate the efficacy of muvalaplin in reducing cardiovascular risk in participants with high lipoprotein(a) who have cardiovascular disease or are at risk of a heart attack or stroke.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Bandana.Poudel@UTSouthwestern.edu
EASi-PROTKT™ - A Study to Test Vicadrostat (BI 690517) Taken Together With Empagliflozin in People With Type 2 Diabetes, High Blood Pressure, and Cardiovascular Disease
This study is open to adults with type 2 diabetes, high blood pressure, and cardiovascular disease. People can join the study if they have these conditions and do not have a history of heart failure. The purpose of this study is to find out if a medicine called vicadrostat, when taken with empagliflozin, helps reduce cardiovascular risk in people with these conditions. The study will compare this combination to a placebo version of vicadrostat with empagliflozin. Participants are put into 2 groups randomly, which means by chance. One group takes vicadrostat and empagliflozin tablets, and the other group takes placebo tablets with empagliflozin. Placebo tablets look like vicadrostat tablets but do not contain any medicine. Participants take a tablet once per day for 2 and a half years and up to 4 years and 3 months. All participants also continue their medication for type 2 diabetes, high blood pressure, and cardiovascular disease. Participants have an equal chance of receiving the study medicine or placebo. Participants are in the study for up to 4 years and 3 months. During this time, they visit the study site regularly. During these visits, doctors collect information about participants' health and take blood samples. The doctors document when participants experience cardiovascular events. The doctors also regularly check participants' health and take note of any unwanted effects.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Jovana.Valdez@UTSouthwestern.edu
A Polypill for Acute Coronary Syndrome (PolyACS)
The current study aims to investigate whether combining the standard medications prescribed after acute coronary syndrome (ACS)-aspirin, P2Y12 inhibitors, and statins-into a single polypill can improve outcomes following an ACS event. Although these therapies are effective, gaps in adherence and uptake significantly contribute to risk or adverse events in the post-ACS period. This study is designed as a pragmatic, multi-center, randomized trial to assess the feasibility and effectiveness of a polypill-based strategy for treatment of ACS.
Call 214-648-5005
studyfinder@utsouthwestern.edu, JuanDavid.CoellarPauta@UTSouthwestern.edu
Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (MARITIME-CV)
The primary objective of this trial is to demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing cardiovascular (CV) morbidity and mortality.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Serrano@UTSouthwestern.edu
XVIVO Heart Box (XHB) With Supplemented XVIVO Heart Solution (SXHS) Continued Access Protocol (CAP) (NIHP-CAP-001)
The purpose of this study is to evaluate if Non-Ischemic Heart Preservation (NIHP) of extended criteria donor hearts using the XVIVO Heart Preservation System (XHPS) is a safe and effective way to preserve and transport hearts for transplantation.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Haley.Mathis@UTSouthwestern.edu
• Age ³18 years.
• Signed informed consent form (ICF).
• Listed for heart transplantation. Exclusion Criteria Recipient:
• Previous solid organ or bone marrow transplantation.
• Requires a multi-organ transplant.
• Subject is enrolled and ongoing in another investigational pharmaceutical or medical device clinical trial (Exception: observational studies are permitted).
• Subject is on mechanical circulatory support pre-transplant other than durable LVAD, Impella or intra-aortic balloon pump (IABP).
• History of complex congenital heart disease ie: single ventricle physiology (per Investigator's discretion and XVIVO review).
• Subject on renal replacement therapy/dialysis.
• Ventilator dependence (subject is intubated at time of transplant/unable to provide consent or re-affirmation of consent).
• Sensitized participants meeting any of the following: * Participant with calculated Panel Reactive Antibody (cPRA) greater than 50% * Participant undergoing any desensitization treatment (also with cPRA less than 50%) * Participant with a positive prospective crossmatch and/or a positive virtual cross match Donor
• Estimated Cross Clamp Time ≥4 hours OR
• Estimated Cross Clamp ≥ 2 hours AND Any one or more of the following: * Age ≥50 years * LVEF 40% - 50% at time of provisional acceptance. (Refer to section 6.3.4 for definition of provisional acceptance). * Down-time ≥20 minutes * Hypertrophy septal thickness \>12 - ≤16mm * Angiographic luminal irregularities with no significant CAD OR 1) Donation after Circulatory Death (DCD) Donor
• Unstable hemodynamics requiring high-dose inotropic support.
• Significantly abnormal coronary angiogram defined as CAD \> 50% stenosis of one or more vessels or if the donor heart exhibits any contusions, structural damage, gross abnormalities, or palpable CAD on final examination.
• Moderate to severe cardiac valve pathology.
• Investigator's clinical decision to exclude from trial.
• Previous sternotomy.
Hyperpolarized 13C Pyruvate-MRI and FDG-PET in a Single Exam for the Prognosis of Ischemic Cardiomyopathy (FDG PET-HP MRI)
This prospective, non-blinded, single-center, translational research study aims to validate a multimodal advanced imaging exam for cardiac viability. The protocol utilizes three distinct imaging modalities: Single Photon Emission Computed Tomography Myocardial Perfusion Imaging (SPECT MPI), 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and Hyperpolarized Carbon-13 (HP-13C) Pyruvate Magnetic Resonance Imaging (MRI). Under this protocol, the SPECT MPI and FDG-PET exams will be used in combination to comprehensively assess myocardial viability. Concurrently, the HP-13C Pyruvate MRI will be utilized to provide additional insights into myocardial metabolism. The study will evaluate healthy volunteers to establish baseline parameters and patients with ischemic cardiomyopathy (ICM) before and after surgical revascularization.
Sarah McNeil, RN sarah.mcneil@utsouthwestern.edu
Cesia Rodriguez Gongora, RN cesia.rodriguezgongora@utsouthwestern.edu
AMBER-HFpEF: Assessment of CK-4021586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF (AMBER-HFpEF)
This is a Phase 2 dose-finding study in adult participants with symptomatic HFpEF.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Daisy.Zambrana@UTSouthwestern.edu
Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction (COMET-HF)
The purpose of this study is to find out if the investigational drug called omecamtiv mecarbil can reduce the risk of the effects of heart failure, like hospitalization, transplantation, or death in patients with heart failure and severely reduced ejection fraction.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Terrell.Martinez@UTSouthwestern.edu
MTOR Inhibitors in Older Adults
Over the past decades, healthcare systems face significant challenges to meet the needs of an aging population due to progressive debility, functional decline and chronic diseases development. While there is a growing appreciation of the potential impact of mTOR inhibitors on slowing aging processes, preventing chronic disease and prolonging healthy lifespan, a major challenge in developing clinical trials to establish the clinical efficacy of mTOR inhibitors is the absence of pharmacokinetics (PK) and pharmacodynamics (PD) data in older adults. The proposed study will provide the foundation for future clinical trials assessing the role of mTOR inhibitors on aging related indications
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alice.Osuji@UTSouthwestern.edu
• Community-dwelling adults
• Patients should be 65 Years and older
• Patients is able to understand and follow trial procedures
• Creatinine clearance \<30 mL/min;
• History of chronic liver disease;
• Uncontrolled Hypertension (i.e., systolic blood pressure \>160 mm Hg);
• Hemorrhagic central nervous system (CNS) event within 1 year from screening visit;
• Thrombotic event (DVT,PE) within 1 year from screening visit if not on anticoagulation;
• Planned major surgical procedures;
• Cardiovascular diseases ( i.e., admission for heart failure or myocardial infarction within 12 months);
• Taking medication that increase or decrease sirolimus blood concentrations;
• Other investigational therapy received within 1 month prior to screening visit;
• History of dementia; 11 Dependence in any Katz Basic Activities of Daily Living.
HIV+ Deceased Donor Heart Transplant Study for HIV+ Recipients
This will be a prospective single-center interventional trial to compare the outcomes of HIV-positive heart transplant recipients by the HIV status of the donor; HIV-positive vs. HIV-negative and learn whether heart organ transplantation from HIV+ deceased donors is as safe and effective in HIV+ recipients as transplants from HIV- deceased donors. Patient will undergo standard evaluation for eligibility of transplantation by the primary heart transplant team. If patient meets eligibility criteria, they will be informed about the study and consent will be obtained. Informed consent will be obtained in a private clinic or inpatient hospital room in a confidential setting. HIV-positive or HIV-negative offers will be made by Organ Procurement and Transplantation Network (OPTN) (serving as a means of "natural randomization" and this information will also be collected, along with the information regarding any information for primary offer declines from the patients as well as other clinical indications to decline an organ offer. As a result of this, there will be two main groups in the study participants that will undergo analysis: 1. patients/recipients that are HIV+ who receive an organ from an HIV+ donor (HIV D+/R+ group) 2. patients/recipients that are HIV+ who receive an organ from an HIV negative donor (HIV D-/R+ group) Only study participants will be able to receive organ offers from both HIV-positive and HIV-negative organ donors whichever is available first regardless of HIV status. This is the only study intervention. Baseline visit parameters will be obtained during a routine heart transplant visit. There will be no additional procedures or blood collection after the baseline study visit. Study data will be collected from chart review of routine post-transplant follow-up visits at weeks 52 (1 year), 104 (2 years), and 152 (3 years) after the transplant.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ricardo.LaHoz@UTSouthwestern.edu
Home-based Cardiac Rehabilitation in Heart Failure
This study evaluates a mobile health (mHealth) home-based cardiac rehabilitation program for patients with heart failure. We will stratify randomization between rural and urban populations, with the goal to assess implementation of cardiac rehabilitation across these two geographic areas. . The study will randomize 332 patients with heart failure (ejection fraction ≥35%) who are not eligible for center-based rehabilitation to either a 12-week mHealth cardiac rehabilitation program or an attention control group, with outcomes measured over 6 months using a composite endpoint of mortality, hospitalizations, and quality of life. We will then assess the implementation of the intervention.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Neil.Keshvani@UTSouthwestern.edu
The ROle of Compression StocKings in Heart Failure Patients (ROCK-HF)
Congestive heart failure (CHF) occurs when the heart is weak and not able to effectively pump blood to the body. One of the common manifestations of CHF is fluid overload and swelling of the legs. Diuretics or "water pills" are usually the treatment for fluid overload and leg swelling; however, in some patients' diuretics are no longer effective or the effectiveness is limited due to poor kidney function. The presence of chronic swelling of the legs could potentially damage the veins; additionally, it could lead to chronic skin changes in the legs and in the worst cases to a leg ulcer. Compression stockings are used in patients with venous diseases to reduce the swelling of the legs and improve mobility and quality of life. Although, there is a theoretical risk that compression stockings might push the fluid of the legs back to the heart and lungs worsening the CHF. The purpose of this study is to determine whether the use of knee-high tight socks (tight stockings with strong compression) vs. knee-high soft socks (soft stockings with minimum compression) are effective in preventing swelling and skin changes and safe in patients with CHF. During the first visit (in-person) a routine medical test will be performed including blood tests, review of the medication doses, current weight, an ultrasound images of the veins, (venous reflux ultrasound), questions about health status and a brief physical exam. The participants will be randomly assigned to receive tight compression vs. soft compression socks. Participants will be asked to wear the socks at least 8 hours a day for 5 days a week. There will be a total of 3 virtual visit (by video or telephone); the first one after one week, then after one month and two months. During the virtual visit participants will be asked about symptoms, current medications and doses, and current weight. The participants are expected to return to the clinic after 3 months for a second in-person visit. During this visit the investigators will ask questions about participant's health, they will perform a brief physical exam of their legs, and check participants weight and medicines; also, a venous ultrasound of the legs, questions about health status will be performed. The duration of the study is 3 months.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Chelsea.Wynn@UTSouthwestern.edu
Investigation of the BrioVAD System for the Treatment of Left Ventricular Heart Failure (INNOVATE)
The goal of this study is to evaluate the safety and efficacy of the BrioVAD System by demonstrating non-inferiority to the HeartMate 3 Left Ventricular Assist System when used for the treatment of advanced, refractory, left ventricular heart failure.
Call 214-648-5005
studyfinder@utsouthwestern.edu, salina.shrestha@utsouthwestern.edu
• Patient is ≥ 18 years of age.
• Patient has received institutional approval for LVAD implantation.
• Patient has a body surface area (BSA) ≥ 1.2 m2.
• Patient is classified as NYHA Class IV with advanced heart failure refractory to advanced heart failure management or NYHA Class III with dyspnea upon mild physical activity.
• Patient has a left ventricular ejection fraction (LVEF) ≤ 25% or LVEF \< 30% on inotropes or temporary MCS.
• Patient is inotrope dependent, OR has a cardiac index (CI) ≤ 2.2 liters/min/m2, while not on inotropes, and also meets one of the following criteria:
• Is on optimal medical management (OMM), based on current heart failure practice guidelines for at least 45 out of the last 60 days and is failing to respond or is not able to tolerate OMM; or
• Has advanced heart failure for at least 14 days and is dependent on an intra-aortic balloon pump (IABP) or temporary mechanical circulatory support device (MCSD) for at least seven days.
• Patient has provided voluntary and informed consent.
• Females of childbearing age agree to use adequate contraception and have a negative pregnancy test.
• Patient's heart failure etiology is related to restrictive or constrictive physiology (e.g., nondilated hypertrophic cardiomyopathy, cardiac amyloidosis/senile or other infiltrative disease), complex congenital heart disease (e.g., transposition of the great vessels), uncorrected thyroid disease, and/or pericardial disease.
• Patient had a myocardial infarction within seven days of study enrollment.
• Patient had cardiothoracic surgery within 30 days of implant with the exception of a procedure to implant temporary MCS: Impella 5.5, Impella CP or TandemHeart.
• Patient has physiological conditions or comorbidities which pose high surgical risk or obstacles as determined by the Investigator.
• Patient has contraindications to warfarin anticoagulation.
• Patient has known hypo- or hypercoagulable state \[e.g., disseminated intravascular coagulation (DIC)\], or has a positive heparin-induced thrombocytopenia (HIT) assay and positive serotonin release assay or requires use of a non-heparin alternative anticoagulation strategy for cardiopulmonary bypass in the judgement of the Investigator.
• Patient is on durable MCS (e.g., LVAD or RVAD).
• Planned need for durable or temporary RVAD support concomitant with LVAD implant.
• Patient is on any form of pre-implant temporary MCS other than isolated LVAD support with an intra-aortic balloon pump, Impella 5.5, Impella CP, or TandemHeart.
• Patient is on any form of pre-implant temporary MCS and has a serum lactate dehydrogenase greater than 2.5 times the upper limits of normal or plasma free hemoglobin \> 40 g/dL.
• Patient has a history of organ transplantation.
• Patient has a mechanical aortic valve that may not be converted to a bioprosthetic valve at the time of VAD implant.
• Patient has a platelet count \< 50 k/μl.
• Patient has a history of confirmed untreated abdominal aortic aneurysm (AAA) \> 5 cm in diameter.
• Patient has moderate or severe aortic insufficiency that will not be corrected during the VAD implant procedure.
• Patient has an uncontrolled systemic infection.
• Patient has a positive COVID 19 test within 21 days of study enrollment and at least one high risk feature including need for supplemental oxygen or ferritin \>1000 ug/L.
• Patient has severe end-organ dysfunction as evidenced by one or more of the following criteria:
• Total bilirubin \> 3.0 mg/dL or cirrhosis confirmed by liver imaging or hemodynamic assessment with or without biopsy confirmation.
• International normalized ratio (INR) ≥ 2.0 or PTT \> 2.5 times control that is not related to anticoagulation therapy.
• Glomerular filtration rate (GFR) \< 30 mL/ min/1.73 m2 or need for renal replacement therapy.
• Severe pulmonary arterial hypertension with a pulmonary vascular resistance (PVR) ≥ 8 Wood units that is not acutely reversible with pharmacologic intervention.
• Severe chronic obstructive pulmonary disease (COPD) or restrictive lung disease requiring home oxygen or an FEV1/FVC \< 0.7 and FEV1 \< 40% predicted.
• Mechanical ventilation for more than three days present at the time of study enrollment.
• Documented history of pulmonary embolism or pulmonary infarct within 60 days of study enrollment.
• History of stroke within 90 days of study enrollment or history of stroke with a mRS ≥ 3 at the time of study enrollment.
• Symptomatic cerebrovascular disease and/or uncorrected carotid stenosis \> 80%.
• Significant peripheral vascular disease (PVD) accompanied by pain at rest or extremity ulceration.
• Pre-albumin \< 15 mg/dL and/or albumin \< 2.5 g/dL.
• Patient has a non-cardiac comorbidity or illness that would limit survival to less than two years.
• Patient has a psychiatric disease or disorder, or irreversible cognitive dysfunction, and/or insufficient social support or a history of non-adherence with medical instructions that is likely to impair study compliance.
• Patient is participating in an interventional clinical trial that may impact or confound the results of the INNOVATE Trial.
MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ruth.Ikpefan@UTSouthwestern.edu
Efficacy of LoDoCo in Improving Exercise Capacity Among Patients With HFpEF and Inflammation
The purpose of this research study is to determine the effectiveness of low dose colchicine (LoDoCo) on measures of exercise capacity, physical function, frailty, and quality of life, among patients with heart failure with chronic stable preserved ejection fraction (HFpEF) and systemic inflammation. The use of LoDoCo in this study is considered investigational as it has not been approved by the Food and Drug Administration (FDA) for the treatment of exercise capacity in patients with HFpEF. Participants will undergo a 1-day screening that includes a blood draw and physical examination. If deemed eligible for the study, participants will undergo a baseline visit within 2 weeks of screening visit that includes physical examination, exercise testing, echocardiography and completion of quality-of-life surveys. Participants will also be randomized at this visit (randomly assigned to a group) to receive either LoDoCo or placebo (inactive substance) for 3 months. Participants will be called back at 3 months for repeat physical examination, blood draws, echocardiography, exercise testing and completion of quality-of-life surveys. Each visit will take about 3 hours. Total study duration is about 3 months.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Bhavik.Bansal@UTSouthwestern.edu
IMPRoving Outcomes in Vascular DisEase - Aortic Dissection (IMPROVE-AD)
The goal of this clinical trial is to determine whether an upfront invasive strategy of TEVAR plus medical therapy reduces the occurrence of a composite endpoint of all-cause death or major aortic complications compared to an upfront conservative strategy of medical therapy with surveillance for deterioration in patients with uncomplicated type B aortic dissection.
Call 214-648-5005
studyfinder@utsouthwestern.edu, christian.marsh@UTSouthwestern.edu
• Age \> 21 years
• Patients with a Stanford type B aortic dissection not involving the aorta at or proximal to the innominate artery, without rupture and/or malperfusion syndrome (renal, mesenteric, or extremity) who are within 48 hours to 6 weeks after start of index admission for their type B dissection
• Ability to provide written informed consent
• Investigator believes anatomy is suitable for TEVAR
• Ongoing systemic infection
• Pregnant or planning to become pregnant in the next 3 months
• Life expectancy related to non-aortic conditions \< 2 years
• Unwilling or unable to comply with all study procedures
• Known patient history of genetic aortopathy
• Penetrating Aortic Ulcer without concomitant uTBAD
• Intramural hematoma without concomitant uTBAD
• Iatrogenic (traumatic) aortic dissection
Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Preserved Ejection Fraction (MUSIC-HFpEF)
The goal of this clinical trial is to test an experimental gene therapy in participants with heart failure with preserved ejection fraction, also known as diastolic heart failure. The main questions it aims to answer are: - safety and tolerability of the gene therapy; and - whether the gene therapy helps the heart ventricles relax during filling. Participants will undergo a one-time infusion of the gene therapy in the cardiac catheterization laboratory and then be followed for safety and effects on left-sided filling pressures while exercising. The first year will have multiple in-person visits followed by 4 years of biannual phone calls.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Therese.Vallina@UTSouthwestern.edu
• Willing and able to provide informed consent
• Negative for anti-AAV1 neutralizing antibodies
• NYHA class II or III
• Left ventricular ejection fraction ≥ 50%
• Evidence of resting or exercise-induced left ventricle filling pressure
• On oral diuretic therapy
• Adequate birth control
• NYHA class IV
• Heart failure requiring hospitalization in the past 3 months
• Manifested or provocable ischemic heart disease
• Atrial fibrillation
• History of congenital heart disease, restrictive or infiltrative cardiomyopathy, hypertrophic cardiomyopathy, acute myocarditis, pericardial disease, uncorrected thyroid disease or discrete left ventricular (LV) aneurysm
• History of amyloidosis
• Untreated left-sided valvular disease
• Severe COPD
• BMI > 50 kg/m^2
• Severe liver, kidney or hematologic dysfunction
• Cancer within the past 5 years
• Unstable concurrent conditions
Prognostic Value of Hyperpolarized 13C MRI for Clinical Myocardial Viability
Heart failure due to coronary artery disease represents a significant cause of mortality. The detection of patients eligible for bypass surgery is a pivotal concern. Nevertheless, the optimal approach for patient selection based on conventional imaging scans remains unclear. The proposed method (Hyperpolarized 13C MRI) has gained extensive use in evaluating in vivo metabolism. This method avoids ionizing radiation and provides critical insights into cardiac function. The feasibility study aims to investigate this method for patient selection before bypass surgery. This innovative imaging technique facilitates the identification of two simple molecules, bicarbonate and lactic acid, produced at high rates by normal heart metabolism. Both bicarbonate and lactate originate from the same precursor molecule, pyruvate. The data generated from this study holds the potential to refine diagnostic precision.
Sarah S McNeil sarah.mcneil@utsouthwestern.edu
Fontan Udenafil Exercise Longitudinal Assessment Trial - 2 (FUEL-2)
This study will evaluate the clinical efficacy and safety of udenafil, an orally administered, potent and selective inhibitor of PDE5, versus placebo for the treatment of adolescent who have had the Fontan procedure.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ana.Garzon@childrens.com
• Males and females with Fontan physiology who are 12 to less than 19 years of age at enrollment.
• Participant consent or parental/guardian consent and participant assent.
• Participant fluency in primary language of country in which study is being conducted.
• Current antiplatelet or anticoagulant therapy.
• Height \< 132 cm.
• Weight \< 40 kg.
• Hospitalization for acute decompensated heart failure within the last 12 months.
• Current intravenous inotropic drugs.
• Undergoing evaluation for heart transplantation or listed for transplantation.
• Diagnosis of active protein losing enteropathy or plastic bronchitis within the last 3 years, or a history of liver cirrhosis.
• Known Fontan baffle obstruction, branch pulmonary artery stenosis, or pulmonary vein stenosis resulting in a mean gradient of \> 4 mmHg between the regions proximal and distal to the obstruction as measured by either catheterization or echocardiography, obtained prior to screening for the trial.
• Single lung physiology with greater than 80% flow to one lung.
• Failure to achieve maximal exertion (defined as RER \< 1.10) on screening/baseline exercise test.
• Peak minute oxygen consumption (VO2) less than 45% or ≥ 80% of predicated for age and gender at enrollment.
• Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within 6 months prior to enrollment.
• Severe valvar regurgitation, ventricular outflow obstruction, or severe aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment.
• History of significant renal (serum creatinine \> 2.0), hepatic (serum AST and/or ALT \> 3 times upper limit of normal), gastrointestinal or biliary disorders that could impair absorption, metabolism or excretion of orally administered medications.
• Inability to complete exercise testing at baseline screening.
• Subjects with a pacemaker whose heart rate at peak exercise is controlled by the extrinsic pacemaker as opposed to a native atrial rhythm.
• History of PDE-5 inhibitor use within 12 months prior to enrollment. (Treatment is defined as chronic therapy as opposed to a single dose.)
• History of any other medication for treatment of pulmonary hypertension within 3 months before study onset.
• Known intolerance to oral udenafil.
• Frequent use of medications or other substances that inhibit or induce CYP3A4.
• Current use of alpha-blockers or nitrates.
• Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results.
• Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results.
• Cardiac care, ongoing or planned, at a non-study center that would impede study completion.
• For females: Pregnancy at the time of screening, pregnancy planned before study completion, or refusal to use an acceptable method of contraception for study duration if sexually active.
• Unable to abstain or limit intake of grapefruit juice and grapefruit containing drinks during the duration of the trial.
• Refusal to provide written informed consent/assent.
• In the opinion of the investigator, the subject is likely to be non-compliant with the study protocol.
• History of clinically significant thromboembolic event, in the option of the site Principal Investigator, that may put the subject at increased risk of a subsequent event while participating in the study.
• Coronavirus disease 2019 (COVID-19) vaccination or symptoms of COVID-19 infection within 7 days of Visit 1.
• Not taking antiplatelet or anticoagulant therapy.
The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation (REACT-AF)
REACT-AF is a multicenter prospective, randomized, open-label, blinded endpoint (PROBE design), controlled trial comparing the current Standard Of Care (SOC) of continuous Direct Oral Anticoagulation (DOAC) use versus time-delimited (1 month) DOAC guided by an AF-sensing Smart Watch (AFSW) in participants with a history of paroxysmal or persistent Atrial Fibrillation (AF) and low-to-moderate stroke risk.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Vukile.Mlambo@utsouthwestern.edu
• 22-85 years of age.
• English speaking participants. Spanish-only speakers may be included in the future at select sites appropriately translated.
• History of non-permanent atrial fibrillation.
• CHA2DS2-VASC score of 1-4 for men and 2-4 for women without prior stroke or Transient Ischemic Attack (TIA), The CHA2DS2-VASc score is a point-based system used to stratify the risk of stroke in Atrial Fibrillation (AF) patients. The acronym CHA2DS2-VASc stands for congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female). Congestive heart failure defined as: The presence of signs and symptoms of either right (elevated central venous pressure, hepatomegaly, dependent edema) or left ventricular failure (exertional dyspnea, cough, fatigue, orthopnea, paroxysmal nocturnal dyspnea, cardiac enlargement, rales, gallop rhythm, pulmonary venous congestion) or both, confirmed by non-invasive or invasive measurements demonstrating objective evidence of cardiac dysfunction and/or ejection fraction \< 40%.
• The participant is on a DOAC at the time of screening and willing to stay on DOAC for duration of study.
• Willing and able to comply with the protocol, including: * Possession of a smart watch-compatible smart phone (iPhone that supports the latest shipping iOS) with a cellular service plan * Be willing to wear the smart watch for the suggested minimum of 14 hours a day * Expected to be within cellular service range at least 80% of the time
• Willing and able to discontinue DOAC
• The participant is willing and able to provide informed consent.
• Valvular or permanent atrial fibrillation.
• Current treatment with warfarin and unwilling or unable to take a DOAC.
• The participant is a woman who is pregnant or nursing.
• The participant is being treated with chronic aspirin, another anti-platelet agent, or chronic NSAIDS outside of current medical guidelines (e.g., primary stroke prevention in patients with atrial fibrillation, primary prevention of cardiovascular events, pain relief, fever, gout) and is unwilling or unable to discontinue use for the study duration.
• Existing cardiac rhythm device or indication for a permanent pacemaker, Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) device or planned insertable cardiac monitor. Insertable cardiac monitors are permitted unless they are being used to guide anticoagulation treatment.
• Known or suspected symptomatic or asymptomatic atrial fibrillation lasting ≥ 1 hour/month over the last 3 months.
• Any documented single AF episode lasting ≥ 1 hour on standard of care or study-provided external cardiac monitor of \> 6 days duration performed within 45 days prior to randomization. Shorter monitoring durations may be acceptable for inclusion at the discretion of the site PI based on the totality of monitoring data and approval of the study PI.
• Ablation for AF within the last 2 months.
• Prior or anticipated left atrial appendage occlusion or ligation.
• Mechanical prosthetic valve(s) or severe valve disease.
• Hypertrophic cardiomyopathy.
• Participant needs DOAC for reasons other than preventing stroke or arterial embolism resulting from AF (i.e., preventing Deep Vein Thrombosis (DVT) or PE) or needs permanent OAC (i.e., congenital heart defects, prosthetic heart valve).
• Participants deemed high risk for non-cardioembolic stroke (i.e., significant carotid artery disease defined as stenosis \> 75%) based on the investigator's discretion.
• The participant is enrolled, has participated within the last 30 days, or is planning to participate in a concurrent drug and/or device study during the course of this clinical trial. Co-enrollment in concurrent trials is only allowed with documented pre-approval from the study manager; there is no concern that co-enrollment could confound the results of this trial.
• The participant has a tattoo, birthmark, or surgical scar over the dorsal wrist area on the ipsilateral side that the AFSW may be worn.
• The participant has a tremor on their ipsilateral side that the AFSW may be worn.
• Any concomitant condition that, in the investigator's opinion, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).
• Known hypersensitivity or contraindication to direct oral anticoagulants.
• Documented prior stroke (ischemic or hemorrhagic) or transient ischemic attack.
• Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism). AF ablation does not constitute reversible AF.
• \> 5% burden of premature atrial or ventricular depolarizations on pre-enrollment cardiac monitoring.
• History of atrial flutter that has not been treated with ablation (participants in atrial flutter and have been ablated are eligible for enrollment).
• Stage 4 or 5 chronic kidney disease.
• Conditions associated with an increased risk of bleeding: * Major surgery in the previous month * Planned surgery or intervention in the next three months that would require cessation of anticoagulation \> 2 weeks. * History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intra- articular bleeding * Gastrointestinal hemorrhage within the past year unless the cause has been permanently eliminated (e.g., by surgery) * Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days * Hemorrhagic disorder or bleeding diathesis * Need for anticoagulant treatment for disorders other than AF * Uncontrolled hypertension (Systolic Blood Pressure \>180 mmHg and/or Diastolic Blood Pressure \>100 mmHg)
The GORE VBX FORWARD Clinical Study: A Comparison of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis to Bare Metal Stenting for Patients With Complex Iliac Occlusive Disease
The objective of this prospective, multicenter, randomized, controlled clinical trial is to demonstrate the superiority of the VBX Device for primary patency when compared to bare metal stenting in complex iliac occlusive disease.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Antonio.SolanoAvendano@UTSouthwestern.edu
DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE)
This study is a prospective, multicenter, randomized controlled trial of an interventional strategy using the ClotTriever System to achieve and maintain vessel patency (ClotTriever Intervention Arm) versus conservative medical management using anticoagulation therapy alone (Conservative Medical Management Arm) in the treatment of subjects with symptomatic unilateral iliofemoral DVT. The study will collect data on demographics, comorbidities, details from the DVT diagnosis and treatment, and clinical outcomes through the 6-month follow up visit.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Camille.Harry@UTSouthwestern.edu
• Age ≥ 18 years
• Proximal lower extremity unilateral DVT involving at least the common femoral, external iliac, or common iliac veins, alone or in combination
• Symptom onset within 12 weeks of enrollment in the study
• Significant symptoms, as defined by a Villalta score > 9
• Willing and able to provide informed consent Exclusion Criteria
• Bilateral iliofemoral DVT
• Prior venous stent in the target venous segment
• IVC aplasia/hypoplasia or other congenital anatomic anomalies of the IVC or iliac veins
• IVC filter in place at the time of enrollment
• Limb-threatening circulatory compromise (e.g., phlegmasia)
• Clot in transit including IVC thrombus presenting as extension of >2cm into the IVC from the CIV
• Symptomatic PE with right heart strain where the physician judges that a DVT intervention is inappropriate at this time.
• Inability to be a candidate for intervention due to medical or technical reasons based on physician judgement
• Severe allergy, hypersensitivity to, or thrombocytopenia from heparin
• Severe allergy to iodinated contrast agents that cannot be mitigated
• Hemoglobin < 8.0 g/dL, INR > 1.7 before warfarin was started, or platelets < 50,000/µl which cannot be corrected prior to enrollment
• Severe renal impairment (estimated GFR < 30 ml/min) in patients who are not yet on dialysis
• Inability to provide therapeutic anticoagulation per Investigator discretion
• Uncontrolled severe hypertension on repeated readings (systolic > 180mmHg or diastolic > 105mmHg)
• Recently (< 30 days) had DVT interventional procedure
• Subject is participating in another study that may interfere with this study
• Life expectancy < 6 months or chronic non-ambulatory status
• Known hypercoagulable states that, in the opinion of the Investigator, cannot be medically managed throughout the study period
• Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject (e.g., contraindication to use of ClotTriever per local approved labeling, compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments)
• Subject has previously completed or withdrawn from this study
• Patient unwilling or unable to conduct the follow up visits per protocol
A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG)
The purpose of this study is to evaluate the safety and tolerability of olezarsen in participants with SHTG.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Lakeisha.Cade@UTSouthwestern.edu
• Satisfactory completion of either ISIS 678354-CS5 or ISIS 678354-CS6 (last dose as scheduled at Week 49) with an acceptable safety profile, per Investigator judgment.
• Participants must be on a stable regimen of lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines.
• Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study, including need for treatment with disallowed medications, or need to change the required stable regimen as per either ISIS 678354-CS5 or ISIS 678354-CS6 study entry criteria. NOTE: Other Inclusion/Exclusion criteria may apply.
Alleviant ALLAY-HF Study
Prospective, multicenter, randomized, sham-controlled, double blinded, adaptive study designed to evaluate the safety and efficacy of a percutaneously created interatrial shunt using the Alleviant ALV1 System in patients with HFpEF/HFmrEF.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Daisy.Zambrana@UTSouthwestern.edu
• Symptomatic HFpEF/HFmrEF with LVEF greater than or equal to 40%
• NYHA Class II, III or ambulatory IV
• Exercise right heart catheterization\*
• Elevated left atrial pressure during exercise right heart catheterization (greater than or equal to 25 mmHg)
• Exercise PVR \< 1.8 WU
• Ongoing stable GDMT
• Advanced heart failure
• Presence of a pacemaker
• Evidence of right heart dysfunction
A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Heart Failure and Inflammation (HERMES)
This study will be done to see if ziltivekimab can be used to treat people living with heart failure and inflammation. Participants will either get ziltivekimab or placebo. Participants will get study medicine for once-monthly injections either in a pre-filled syringe to inject the study medicine into a skinfold or a pen-injector to inject the study medicine into flat skin. The study is expected to last for up to 4 years. Participants will have up to 20 clinic visits. Participants will have to use a study app on their phone to record and share information about all their injections of study medicine and to fill in questionnaires.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Daniel.Ayodele@UTSouthwestern.edu
• N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than equal to 300 picograms per milliliter (pg/mL) at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NTproBNP must be greater than equal to 600 pg/mL. Note that the screening electrocardiogram (ECG) must be obtained the same day as sampling for NT-proBNP.
• Hospitalisation or urgent/unplanned visit with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment, within the last 9 months prior to screening (visit 1) in combination with NT-proBNP greater than equal to 200 pg/mL at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NT-proBNP must be greater than equal to 600 pg/mL. * Diagnosis of heart failure (New York Heart Association \[classification\] \[NYHA\] Class II-IV). * Left ventricular ejection fraction (LVEF) greater than 40 percentage (%) documented by echocardiography within 12 months prior to or at screening (visit 1). The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction (e.g., myocardial infarction \[MI\] or heart failure \[HF\] hospitalisation). * Structural heart disease and/or functional heart disease documented by echocardiography within 12 months prior to or at screening (visit 1) showing at least one of the following: * Left atrial (LA) volume index greater than 34 milliliter per meter square (mL/m\^2). * LA diameter greater than equal to 3.8 centimeter (cm). * LA length greater than equal to 5.0 cm. * LA area greater than equal to 20 cm square. * LA volume greater than equal to 55 milliters (mL). * Intraventricular septal thickness greater than equal to 1.1 cm. * Posterior wall thickness greater than equal to 1.1 cm. * Left ventricular (LV) mass index greater than equal to 115 grams per meter square (g⁄m\^2 ) in men or greater than equal to 95 g⁄m\^2 in women. * E/e' (mean septal and lateral) greater than equal to 10. * e' (mean septal and lateral) less than 9 centimeter per second (cm/s). * No heart failure hospitalisations or urgent heart failure visits between screening (visit 1) and randomisation (visit 2).
• Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
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.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Amy.Browning@UTSouthwestern.edu
Heat Waves and the Elderly - Cooling Modalities
The purpose of this study is to assess how well cooling modalities work in reducing cardiovascular stress of the elderly to heat wave conditions
Call 214-648-5005
studyfinder@utsouthwestern.edu, craig.crandall@utsouthwestern.edu