Reducing Heart Failure Risk in Late-Life With Physical Activity

March 10, 2026 updated by: Sheila M. Hegde, MD, Brigham and Women's Hospital

Reducing Heart Failure Risk in Late-Life With Physical Activity: Impact on Cardiac Structure and Function and Proteomic Signatures

The goal of this clinical trial is to learn about the molecular pathways associated with the benefit of a regular exercise program in patients with high blood pressure and who don't already participate in regular exercise.

The main question it aims to answer is to identify protein signatures associated with the benefits of a cardiac rehabilitation exercise program.

The trial will enroll 42 participants, who will be randomized to a 12 week cardiac rehabilitation exercise program versus control arm and asked to participate in the following at the beginning and end of study:

  • Cardiopulmonary exercise test (CPET)
  • Echocardiogram
  • Physical function test
  • 6-minute walk test
  • Hand grip strength
  • Quality of life questionnaire
  • Blood draws

Researchers will compare results between those who do and don't participate in the exercise program.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Lifestyle modification with physical activity (PA) appears to be protective of several age-related cardiovascular (CV) outcomes, including heart failure (HF), in a dose-dependent manner. While many studies with exercise training have demonstrated improvement in quality of life and cardiorespiratory fitness, findings have not been consistent with regards to the potential for exercise to preserve or even improve cardiac function in adults with HF. There remains incomplete understanding of the molecular pathways by which PA mitigates HF risk. Furthermore, exercise studies often exclude older adults, who are disproportionately affected by HF, though our preliminary data suggest the protective effects of PA extend to late-life. Older adults are at particularly heightened risk for HF with preserved ejection fraction (HFpEF), which is characterized by impaired left ventricular (LV) diastolic function and impaired systolic deformation despite preserved LV ejection fraction (LVEF). Unlike with HF with reduced ejection fraction (HFrEF), effective pharmacologic therapies or interventions to improve cardiac function among individuals with preserved LVEF are limited. Thus, there is a critical need to define the cardiovascular mechanisms by which PA impacts HF risk in older adults that may enable the identification of novel therapeutic targets to prevent HF and HFpEF in particular.

As proteins orchestrate and carry out cellular functions in health and in diseases, one method of characterizing changes in CV function is to investigate cell signaling by studying the circulating proteome. Proteomic approaches have previously been used to identify pathways relevant to myocardial infarction and have also been used to investigate molecular pathways characterizing PA and CV disease. A recent study demonstrated upregulation of inflammation-related proteins in HFpEF patients (n=228) compared to controls, and their association with worse indices of cardiac function. Specific proteomic patterns have also been associated with aerobic exercise, with 2 proteomic modules that were specifically preserved with aging in habitual exercisers. Data from Swedish cohorts has also shown an association of leisure-time PA with 28 CV-specific proteins involved in atherosclerotic processes. Serial multi-omic measures (including proteomics) have been used to demonstrate marked intra-individual changes in circulating proteins with acute exercise. More recently, high-throughput proteomic profiling has been successfully employed in younger adults to identify baseline protein levels associated with change in cardiorespiratory fitness following an exercise intervention. However, to-date, limited data exist regarding intervention-related changes in the proteome in older adults at risk for HF and the extent to which these changes correlate with changes in cardiorespiratory fitness.

Supervised exercise-training with cardiac rehabilitation (CR) has been well established as an effective method to improve maximal oxygen consumption (VO2 max), a measure of cardiorespiratory fitness. Improvement in VO2 max has also been demonstrated with exercise training in sedentary older adults over 65 years of age.

The objective of this proposal is to identify protein signatures characterizing the known benefits of a structured CR program on VO2 max. Our working hypotheses is that proteomic approaches will identify novel biomarkers that uniquely characterize molecular pathways associated with exercise training and CR-related changes in proteins will correlate with changes in VO2 max. Successful completion of this aim will identify possible novel protein signatures underlying the protective biological pathways mediated by a structured CR program that may be used as preliminary data for future grant proposals.

Aim: Identify molecular pathways underlying the beneficial effect of a structured PA intervention on functional capacity with the use of plasma proteomics in older sedentary adults at high risk of HF. (BWH-based cohort). Hypotheses: (1) Randomization to participation in a cardiac rehabilitation (CR) program will result in improvement in circulating levels of 4 plasma proteins associated with change in VO2max, a measure of cardiorespiratory fitness, and with genetic evidence supporting a causal effect on HF and cardiac structure (ATF6, STC1, JAG1, PTK7). The investigators will randomize 42 sedentary adults at high risk of HF (stage B HF) to participation in a CR program and perform proteomic analysis, cardiopulmonary exercise testing, and echocardiography at baseline and 12 weeks.

Study Type

Interventional

Enrollment (Estimated)

42

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Hypertension (controlled on stable medication regimen)
  • Structural heart abnormality (LVH or LA enlargement)
  • LVEF > 50%
  • Sedentary
  • BMI <30

Exclusion Criteria:

  • Diabetes
  • Unable to exercise
  • Supplemental oxygen use
  • Pulmonary hypertension
  • Sleep apnea
  • Regular exercise training
  • Devices that limit ability to achieve target heart rate
  • Moderate to severe valve disease
  • Recent (within 3 months) major CV event or planned procedures (within 6 months)
  • Terminal illness, life expectancy <6 months
  • Inability or unwillingness to comply with study requirements
  • No access to smart phone/tablet

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cardiac Rehabilitation
Participants will participate in a 12-week cardiac rehabilitation program
Behavioral: Cardiac Rehabilitation
Participation in a 12-week cardiac rehabilitation program
Placebo Comparator: Attention Control
Participants will not participate in a cardiac rehabilitation program and will receive phone calls in place of cardiac rehabilitation visits.
Behavioral: Attention Control
Participants will receive regular phone calls in place of cardiac rehabilitation visits

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact of Cardiac Rehabilitation training on single protein changes
Time Frame: 12 weeks
Change in protein levels assessed by blood draws and measured by Somascan assay. ANCOVA analysis adjusting for baseline protein levels with intention to treat group assignment
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of change in proteins with change in VO2 max
Time Frame: 12 weeks
Correlation of single protein changes associated with change in VO2 max
12 weeks
Correlation of change in proteins with change in LV global longitudinal strain
Time Frame: 12 weeks
Correlation of single protein changes associated with change in LV global longitudinal strain
12 weeks
Correlation of change in proteins with change in LV diastolic function
Time Frame: 12 weeks
Correlation of single protein changes associated with change in LV diastolic function
12 weeks
Correlation of change in proteins with change in VE/VCO2
Time Frame: 12 weeks
Correlation of single protein changes associated with change in VE/VCO2
12 weeks
Correlation of change in proteins with change in Short Physical Performance Battery (SPPB)
Time Frame: 12 weeks
Correlation of single protein changes associated with change in Short Physical Performance Battery (SPPB)
12 weeks
Correlation of change in proteins with change in 6-minute walk test
Time Frame: 12 weeks
Correlation of single protein changes associated with change in 6-minute walk test
12 weeks
Correlation of change in proteins with change in grip strength
Time Frame: 12 weeks
Correlation of single protein changes associated with change in grip strength
12 weeks
Correlation of change in proteins with change in EQ-5D (QOL)
Time Frame: 12 weeks
Correlation of single protein changes associated with change in EQ-5D (QOL)
12 weeks
Correlation of change in proteins with change in step counts
Time Frame: 12 weeks
Correlation of single protein changes associated with change in step counts
12 weeks
Correlation of baseline proteins with change in VO2 max
Time Frame: 12 weeks
Correlation of baseline proteins with change in VO2 max
12 weeks
Correlation of baseline proteins with change in LV global longitudinal strain
Time Frame: 12 weeks
Correlation of baseline proteins with change in LV global longitudinal strain
12 weeks
Correlation of baseline proteins with change in LV diastolic function
Time Frame: 12 weeks
Correlation of baseline proteins with change in LV diastolic function
12 weeks
Correlation of baseline proteins with change in VE/VCO2
Time Frame: 12 weeks
Correlation of baseline proteins with change in VE/VCO2
12 weeks
Correlation of baseline proteins with change in SPPB
Time Frame: 12 weeks
Correlation of baseline proteins with change in SPPB
12 weeks
Correlation of baseline proteins with change in 6-minute walk test
Time Frame: 12 weeks
Correlation of baseline proteins with change in 6-minute walk test
12 weeks
Correlation of baseline proteins with change in grip strength
Time Frame: 12 weeks
Correlation of baseline proteins with change in grip strength
12 weeks
Correlation of baseline proteins with change in EQ-5D (QOL)
Time Frame: 12 weeks
Correlation of baseline proteins with change in EQ-5D (QOL)
12 weeks
Correlation of baseline proteins with change in step counts
Time Frame: 12 weeks
Correlation of baseline proteins with change in step counts
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Investigators

  • Principal Investigator: Sheila Hegde, MD, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

January 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

January 23, 2024

First Submitted That Met QC Criteria

January 30, 2024

First Posted (Actual)

February 8, 2024

Study Record Updates

Last Update Posted (Actual)

March 12, 2026

Last Update Submitted That Met QC Criteria

March 10, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023p002781

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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