Bcl-2 Anathogene-3 (BAG3) Dilated Cardiomyopathy (DCM), Cardiomyopathy, Dilated
Conditions
Keywords
BAG3, DCM, cardiomyopathy, dilated cardiomyopathy, heritable heart disease, heart disease
Brief summary
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 three years. During this time, participants will visit the site at least 8 times (about every 3 months for the first year and annually during year 2 and three). 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.
Interventions
None listed
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented BAG3 mutation that causes or is likely to cause dilated cardiomyopathy * Heart failure Stage B-D, New York Heart Association (NYHA) Class I-IV * Left Ventricular Ejection Fraction ≤50% (i.e., Reduced Heart Function)
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine baseline of cardiac structure and function in BAG3 associated DCM. | Baseline | Baseline measures of left ventricular volumes at end systole and diastole using imaging at baseline. |
| Determine changes over time in cardiac structure and function in BAG3 associated DCM. | 3 years | Changes over time of left ventricular volumes at end systole and diastole using imaging over the course of 3 years follow up time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in high sensitivity troponin I (hsTNI) levels | Baseline to year 3 | HsTNI will be collected at baseline through 3 years to observe the natural history (baseline and variance) of the biomarker and the correlation of hsTNI to severity of clinical disease progression. |
| Change from Baseline in high sensitivity troponin T (hsTNT) levels | Baseline to year 3 | HsTNT will be collected at baseline through 3 years to observe the natural history (baseline and variance) of the biomarker and the correlation of hsTNT to severity of clinical disease progression. |
| Change from Baseline in N-terminal Prohormone of Pro-Brain-Type Natriuretic peptide (NT-proBNP) levels | Baseline to year 3 | NT-proBNP will be collected at baseline through 3 years to observe the natural history (baseline and variance) of the biomarker and the correlation of NT-proBNP to severity of clinical disease progression. |
| Change from baseline in Measures of Oxygen Capacity | Baseline to year 3 | Measured via Cardio Pulmonary Exercise Testing (CPET). |
| Change from Baseline in Scores of Kansas City Cardiomyopathy Questionnaire (KCCQ) domains | Baseline to year 3 | — |
| Change from Baseline in Scores of Patient Global Impression of Severity (PGI-S) | Baseline to year 3 | — |
| Change from Baseline in Scores of Patient Global Impression of Change (PGI-C) | Baseline to year 3 | — |
| Define the rate of cardiac status changes over time. | 3 years | The frequency and rate of incidence of death, heart transplant, MCS, heart failure, hospitalization, appropriate implantable cardioverter defibrillator shock, or aborted SCD. |
Countries
Netherlands, Poland, Spain, United Kingdom, United States
Outcome results
None listed