A Study About the Natural History in Adults With BAG3 Dilated Cardiomyopathy (a Type of Heart Disease)

Study Overview
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Brief Summary
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The purpose of this study is to learn about the natural progression of DCM (dilated cardiomyopathy) caused by BAG3 gene mutations. DCM is a condition as the heart muscle is weakened and the heart becomes enlarged. This makes it hard for the heart to pump enough blood for the body. The study is seeking up to about 35 participants who have: BAG3 mutation (change in the gene) that causes or is likely to cause dilated cardiomyopathy NYHA (New York Heart Association) Class I-IV at screening (Stage B-D) Left Ventricular Ejection Fraction less than or equal to 50% (meaning reduced heart function) All participants in this study will receive their usual treatment. The investigators will observe the natural progression of people who have BAG3 DCM. This will help the investigators better understand the disease and aid in future research. Participants will take part in this study for one year. During this time, participants will visit the site at least 4 times (about every 3 months). Participants will undergo study procedures and give information about their health. These procedures will include a physical exam, cardiac magnetic resonance imaging, echocardiography, ECG monitoring, activity monitoring, cardiopulmonary exercise testing, and blood tests. Participants will answer questions about health and quality of life. The study team will also call participants about 1 time over the phone.

Official Title
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A PROSPECTIVE MULTINATIONAL STUDY OF THE NATURAL HISTORY OF PARTICIPANTS WITH BAG3 MUTATION ASSOCIATED DILATED CARDIOMYOPATHY

Conditions
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Cardiomyopathy, Dilated, Bcl-2 Anathogene-3 (BAG3) Dilated Cardiomyopathy (DCM)

Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented BAG3 mutation that causes or is likely to cause dilated cardiomyopathy New York Heart Association (NYHA) Class I-IV at screening (Stage B-D) Left Ventricular Ejection Fraction ≤50% (i.e., Reduced Heart Function) Key Exclusion Criteria: Acute decompensated heart failure within 1 month prior to enrollment.(such as hospitalization) Any of the following within 3 months prior to screening: myocardial infarction (MI), cardiac surgical procedures (other than for pacemaker/ICD/CRT-defibrillator [CRT-D] implantation), acute coronary syndrome, or hospitalization for cardiac arrhythmia. History of heart transplantation eGFR <30 mL/min/1.73 m2 (significantly impaired kidney function) Noncardiac condition that limits lifespan to <1 year. Presence of other form(s) of cardiomyopathy contributing to heart failure Previous administration with an investigational drug within 30 days (or as determined by the local requirement). No more than 3 first-degree members of the same family who are already participating in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| BAG3 DCM<br>A single arm observational trial where all participants will undergo the same schedule of assessments. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine changes over time in cardiac structure and function in BAG3 associated DCM. | Changes over time of left ventricular volumes at end systole and diastole using imaging over the course of one year follow up time. | 1 year | 
| Determine baseline of cardiac structure and function in BAG3 associated DCM. | Baseline measures of left ventricular volumes at end systole and diastole using imaging at baseline. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in high sensitivity troponin I (hsTNI) levels | HsTNI will be collected at baseline through 1 year to observe the natural history (baseline and variance) of the biomarker and the correlation of hsTNI to severity of clinical disease progression. | Baseline to 1 year | 
| Changes in high sensitivity troponin T (hsTNT) levels | HsTNT will be collected at baseline through 1 year to observe the natural history (baseline and variance) of the biomarker and the correlation of hsTNT to severity of clinical disease progression. | Baseline to 1 year | 
| Changes in N-terminal Prohormone of Pro-Brain-Type Natriuretic peptide (NT-proBNP) levels | NT-proBNP will be collected at baseline through 1 year to observe the natural history (baseline and variance) of the biomarker and the correlation of NT-proBNP to severity of clinical disease progression. | Baseline to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DCM, BAG3, cardiomyopathy, dilated cardiomyopathy, heritable heart disease, heart disease