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

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 patients with a primary endpoint of change in peak VO2.

Forty-eight participants with HFpEF who are overweight or obese will be recruited from the Cardiopulmonary Exercise Testing (CPET) Laboratory and will have a recent or scheduled clinical care CPET. These measurements will serve as baseline measures. After undergoing other baseline measurements such as actigraphy, blood studies, DEXA scan, Kansas City Cardiomyopathy Questionnaire (KCCQ), NIHTB-CB, and RAVLT, participants will be randomized (1:1) to either activin-ligand trap biological therapy combined with physical activity (n=24) or placebo combined with physical activity (n=24). Randomization will be stratified by sex and will be performed in permutated blocks of 4 to assure balanced group sizes. In order to allocate without bias and in a manner blinded to both participants and investigators, we will use random number generation at the time of randomization. After 12 weeks, patients will return for a new CPET, physical exam, urine and blood test, echocardiogram, electrocardiogram, DEXA scan, actigraphy, assessment of NYHA class, NIHTB-CB, RAVLT, KCCQ, six-minute walk test, handgrip test, and adverse events assessment. After these assessments, patients will undergo crossover at week 12 and will receive either the activin-ligand trap biological therapy combined with physical activity (n=24) or the placebo combined with physical activity (n=24) for an additional 12 weeks. At week 24, patients will return to have a repeat of the same tests that were performed at week 12.