Status:

NOT_YET_RECRUITING

EXercise and Activin Inhibition to Modulate InflammatioN Effects on Heart Failure and Cognition (EXAMINE-HFC)

Lead Sponsor:

Massachusetts General Hospital

Collaborating Sponsors:

American Heart Association

University of Michigan

Conditions:

Heart Failure With Preserved Ejection Fraction

Eligibility:

All Genders

40+ years

Phase:

PHASE2

Brief Summary

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...

Detailed Description

A double-blind, prospective, phase 2 randomized, placebo-controlled 24-week clinical trial to assess exercise tolerance after activin-ligand trap biological therapy compared to placebo in HFpEF patien...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

November 1 2025

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

August 1 2027

Estimated Enrollment :

48 Patients enrolled

Trial Details

Trial ID

NCT07202000

Start Date

November 1 2025

End Date

August 1 2027

Last Update

October 1 2025

Active Locations (1)

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1

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114