NCT07202000 · Massachusetts General Hospital
EXercise and Activin Inhibition to Modulate InflammatioN Effects on Heart Failure and Cognition (EXAMINE-HFC)
(EXAMINE-HFC)
What this study is about
The goal of this clinical trial is to learn if therapy with activin ligand-trap biological therapy (an experimental drug) combined with exercise training can improve exercise capacity and cognitive function in heart failure with preserved ejection fraction (HFpEF).
View original scientific description
The goal of this clinical trial is to learn if therapy with activin ligand-trap biological therapy (an investigational drug) combined with exercise training can improve exercise capacity and cognitive function in heart failure with preserved ejection fraction (HFpEF). The main questions it aims to answer are: * Does activin-ligand trap biological therapy improve exercise capacity as measured by change in peak oxygen uptake (peak VO2) from baseline to week 12? * Does activin-ligand trap biological therapy improve cognitive function as assessed by the NIH-Toolbox Cognition Battery (NIHTB-CB) composite score and Rey Auditory Verbal Learning Test (RAVLT) from baseline to week 12? Researchers will compare activin-ligand trap biological therapy to a placebo (a look-alike substance that contains no drug) to see if activin-ligand trap therapy works to improve exercise capacity and cognitive function in patients with HFpEF.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Adult ≥ 40 years of age;
- Body mass index ≥ 27 kg/m2;
- Left ventricular ejection fraction (LVEF) ≥ 0.50 with NYHA II-III;
- Established diagnosis of HFpEF based on medical history supported by at least one of the following 5 criteria (i through v, below) i. Documented hospitalization with HFpEF as a primary cause or other urgent outpatient visit for acute HFpEF (as primary cause) at which IV loop diuretic was provided as treatment (≥ 1 month prior to screening); ii. Increased left atrial (LA) size: AP dimension: ≥ 4.0 in men, \> 3.8 in women; or LA length ≥ 5.0 cm or LA volume ≥ 55 mL or LA volume index≥ 29 mL/m2; iii. PCWP at rest \> 15 mmHg (or LVEDP ≥ 18 mmHg) or ≥ 25 mmHg with exercise (or PCWP/CO ≥ 2.0 mmHg/L/min with exercise); iv. Either of the following at rest by Doppler and Tissue Dopper: a) for patients in sinus rhythm: E/e' ratio ≥ 15 at septal annulus, or E/e' ratio ≥ 13 at lateral annulus, or average E/e' ratio ≥ 14; for patients in atrial fibrillation E/e' ≥ 11 at the septal annulus; v. Elevated NT-proBNP ≥ 125 pg/mL (≥ 250 with chronic atrial fibrillation).
- Achievement of a respiratory exchange ratio (RER) at baseline CPET of ≥ 1.05 to ensure maximum volitional effort was provided;
- Ambulatory (not wheelchair/scooter-dependent) and able to perform CPET/6MWT/Chair stand evaluations;
- Stable dose of medications (defined as no new medication or change in existing dose of medication ≥ 50%) for at least 30 days prior to screening.
Exclusion criteria
- Conditions anticipated to independently impact exercise capacity or clinical stability during the trial period
- Current or recent (within 30 days) acute decompensated HF requiring intravenous diuretics or hospitalization;
- Initiation of treatment with GLP-1 receptor agonist or SGLT2 inhibitor within 60 days of screening;
- Planned cardiac surgery or catheter intervention during the period of trial participation;
- Entry within 30 days of screening or plans to enter a weight loss program and/or cardiac rehabilitation or initiate any new exercise program during the study.
- Primary cardiomyopathy (e.g., constrictive, restrictive, infiltrative, toxic, hypertrophic, congenital), LVEF \< 40% within the last 3 years, or active myocarditis;
- Lactating, pregnant, or planning to become pregnant;
- Non-cardiac organ system dysfunction or sufficient severity to predominate as the source of exercise intolerance in addition to the following specific criteria: pulmonary disease with chronic home daytime supplemental O2 dependence, severe anemia with hemoglobin \< 9 g/dL or chronic kidney disease (CKD) with estimated GFR \< 30 mL/min/1.73m2 based on the CKD-EPI equation.
Where
- Boston, Massachusetts
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 9, 2026 · Source of record for eligibility and locations