Identifying Markers of Exercise Training in Heart Failure

Study Overview
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Brief Summary
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The heart failure syndrome that occurs when the heart is too sick to properly do its job. One of the main symptoms is difficulty with exercise. One way to improve symptoms is to start patients in a 12 week exercise program called cardiac rehabilitation. Cardiac rehabilitation been shown to improve symptoms for heart failure patients. However, we do not know exactly what exercise does to the molecules that make up the human body. If we could answer this question, we might find a whole new way to treat the symptoms of heart failure. Therefore we want to know what molecules might be responsible for the benefits of exercise. The plan for this study is to measure the levels of thousands of proteins in blood samples which come from people with heart failure and see how those levels change after 12 weeks of cardiac rehabilitation, compared to the protein levels in patients whose cardiac rehabilitation is delayed until after the study period. If we know the proteins that change with exercise, we can then look to see if targeting these proteins with medicines can mimic the benefits of exercise. The long term goal of our work is to identify exercise-in-a-pill medicines that will help people with heart failure.

Official Title
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Identifying Markers of Exercise Training in Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Behavioral: Cardiac rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be 18-89 years of age Not be pregnant or lactating in the last 12 months, or planning to become pregnant for the next 4 months. A pregnancy test will be performed on the day of DXA scan in women of child-bearing potential. Not be post-partum during the last 12 months. patients must carry a diagnosis of heart failure with ejection fraction < 40% Be willing to provide informed consent for all study procedures be willing to participate in cardiac rehabilitation Exclusion Criteria: Diabetes (self-report and screening tests), which includes: i) treatment with any hypoglycemic agents (self-report, even for non-diabetic reasons) or ii) fasting glucose >125 or A1c >6.4 (screening test). Chronic renal insufficiency (screening test): estimated glomerular filtration rate <60 mL/min/1.73 m2 from serum creatinine (mg/dL) by the Chronic Kidney Disease Epidemiology Collaboration equation Individuals receiving any active treatment for autoimmune disorders (including monoclonal antibodies) within the last 6 months. Alcohol consumption (self-report): i) more than 7 drinks per week for women and more than 14 drinks per week for men; ii) history of binge drinking. Hospitalization for any psychiatric condition within one year (self-report). Any musculoskeletal or ligamentous injury, amputation or congenital neurological defect that, in the opinion of the team clinician, would negatively impact or mitigate participation in and completion of the protocol. Mental incapacity and/or cognitive impairment on the part of the participant that would inhibit adequate understanding of or cooperation with the study protocol. Taking Androgenic anabolic steroids, anti-estrogens, anti-androgens Taking Growth hormone, insulin like growth factor-I, growth hormone releasing hormone Taking Any drugs used to treat diabetes mellitus or to lower blood glucose Taking Any drugs used specifically to induce weight loss Taking Any drugs used specifically to induce muscle growth/hypertrophy or augment exercise-induced muscle hypertrophy Taking Narcotics and narcotic receptor agonists Taking Monoclonal antibodies Taking Any other medications that, in the opinion of local clinicians, would negatively impact or mitigate full participation and completion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12 weeks Cardiac Rehabilitation<br>Participants will be randomized to either immediate entry to cardiac rehabilitation, or no intervention (their clinical cardiac rehabilitation will be delayed during the 12 weeks of the study) | Behavioral: Cardiac rehabilitation<br>* 12 week program of standard clinical cardiac rehabilitation for patients with symptomatic heart failure. Patients undergo 3-times weekly sessions of monitored exercise for 12 weeks. This is the same cardiac rehabilitation patients would get as part of clinical care.<br>|
| No Intervention: Standard of Care<br>Participants will be randomized to either immediate entry to cardiac rehabilitation, or no intervention (their clinical cardiac rehabilitation will be delayed during the 12 weeks of the study) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Proteomic Profile | Patients will have proteomic profiling performed at baseline, prior to the intervention period, and again following the 12 week intervention. Proteomic profiling measures levels of  3000 proteins in the blood, so the changes in the global proteome can be assessed after the intervention period. | Baseline vs week 12 proteomic profile |