Activation-ligand trap therapy with exercise to help HFpEF patients

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase 2, double-blind, randomized, placebo-controlled trial enrolling about 48 adults with overweight or obesity and heart failure with preserved ejection fraction. Participants will receive activin-ligand trap therapy or placebo for 12 weeks, in addition to a structured physical activity program, with assessments including CPET for exercise capacity and neurocognitive tests. Primary endpoint is change in peak VO2 from baseline to week 12; secondary endpoints include cognitive function changes measured by NIHTB-CB and RAVLT. After week 12, a crossover will occur so all participants may receive the active therapy. The study is conducted at Massachusetts General Hospital with multiple collaborators and uses stratified randomization by sex to balance groups.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Adult ≥ 40 years of age;
2. Body mass index ≥ 27 kg/m2;
3. Left ventricular ejection fraction (LVEF) ≥ 0.50 with NYHA II-III;
4. 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).
5. Achievement of a respiratory exchange ratio (RER) at baseline CPET of ≥ 1.05 to ensure maximum volitional effort was provided;
6. Ambulatory (not wheelchair/scooter-dependent) and able to perform CPET/6MWT/Chair stand evaluations;
7. 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:

1. Conditions anticipated to independently impact exercise capacity or clinical stability during the trial period

   1. Current or recent (within 30 days) acute decompensated HF requiring intravenous diuretics or hospitalization;
   2. Initiation of treatment with GLP-1 receptor agonist or SGLT2 inhibitor within 60 days of screening;
   3. Planned cardiac surgery or catheter intervention during the period of trial participation;
   4. 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.
2. Primary cardiomyopathy (e.g., constrictive, restrictive, infiltrative, toxic, hypertrophic, congenital), LVEF \< 40% within the last 3 years, or active myocarditis;
3. Lactating, pregnant, or planning to become pregnant;
4. 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 it's running

• Massachusetts General Hospital
  Boston, Massachusetts, United States Recruiting

Study contacts

• Principal investigator: Gregory D. Lewis, MD — Massachusetts General Hospital
• Study coordinator: Gregory D. Lewis, MD
• Email: glewis@partners.org
• Phone: 617-724-9254

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Remote rehabilitation for HFpEF patients using telerehabilitation

  A home-based telerehabilitation program is being tested to see if it is safe and helpful for people with heart failure with preserved ejection fraction.

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• EDG-15400 in adults with HFpEF: a phase 2 study

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• Incretin therapy with tirzepatide for obesity-related HFpEF

  A 15-month study will test whether tirzepatide helps people with obesity and HFpEF by reducing plasma volume.

  Recruiting Phase 4 Columbia University · New York, New York · NCT07554638

• Boosted exercise with group coaching for HFpEF

  This trial tests a blended, guided exercise program with group coaching and remote monitoring to see if it helps older adults with HFpEF improve activity and health at a lower cost.

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• Exercise cardiac MRI for heart failure with preserved ejection fraction

  This study will try low-field exercise cardiac MRI to see if it can diagnose, describe, and predict risk in people with HFpEF compared with those who have non-cardiac breathlessness and healthy volunteers.

  Recruiting Mayo Clinic · Rochester, Minnesota · NCT07401771

• HRS-1893 for heart failure with preserved ejection fraction

  This trial will test whether HRS-1893 is safe and tolerable in adults aged 40 and older who have heart failure with preserved ejection fraction.

  Recruiting Phase 2 Shandong Suncadia Medicine Co., Ltd. · Shanghai, Shanghai Municipality · NCT07269717

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.