Identifying Markers of Exercise Training in Heart Failure

NCT05696652 | Recruiting DMC

• 3 other identifiers: 688275K23HL164980-0223CDA1040581
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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, the investigators do not know exactly what exercise does to the molecules that make up the human body. If the investigators could answer this question, the investigators might find a whole new way to treat the symptoms of heart failure. Therefore the investigators 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 the investigators know the proteins that change with exercise, the investigators 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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (2)

• Change in Proteomic Profile: Chronic

  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

• Change in Proteomic Profile: Acute

  Patients will have proteomic profiling performed at baseline, prior to the acute bout of exercise, 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 before and after the acute exercise bout. Comparisons can be drawn between between those exercising and those not exercising (at acute bout #1), but also can be compared between those who did and did not not undergo cardiac rehabilitation (at acute bout #2).

  Acute bout vs control; Baseline vs week 12 proteomic profile of acute exercise

Secondary Outcomes (1)

• Proteomic predictors of Cardiopulmonary fitness

  Baseline vs week 12 proteomic profile

Study Arms (4)

Active arm: Acute exercise

EXPERIMENTAL

This arm includes two-thirds of enrollees and focuses on acute effects of exercise. Qualifying participants with heart failure randomized to this arm will undergo a 40 minute bout of moderate intensity exercise. Blood samples will be collected before and after the acute bout at 10, 30, and 210 minutes after exercise.

Behavioral: Acute exercise

Control arm: No exercise (Acute Comparison)

NO INTERVENTION

This arm includes one-third of enrollees and serves as control. Qualifying participants with heart failure randomized to this arm will begin with a 40 minute period of rest. Blood samples will be collected before and after the the 40 minute period at 10, 30, and 210 minutes after the start.

Active Arm: 12 weeks Cardiac Rehabilitation

EXPERIMENTAL

This arm includes two-thirds of enrollees for the training intervention and focuses on chronic effects of exercise. Participants have a baseline blood sample and then go to cardiac rehabilitation for a 12 week period. A single blood sample will be obtained at 6 weeks. The participants will return after the 12 weeks of cardiac rehabilitation for another single blood sample.

Behavioral: Cardiac rehabilitation

Control: No Exercise (Training)

NO INTERVENTION

Participants receive baseline fasting blood sample and then defer cardiac rehabilitation for a 12 week period. A single blood sample will be obtained at 6 weeks of this control intervention period. 12 weeks after enrollment, patients will return for another single blood sample.

Interventions

Acute exercise BEHAVIORAL

40 minute moderate intensity exercise bout on a treadmill. This is similar to a single session of cardiac rehabilitation.

Active arm: Acute exercise

Cardiac rehabilitation BEHAVIORAL

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.

Active Arm: 12 weeks Cardiac Rehabilitation

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18-89
• Patients must carry a diagnosis of heart failure with ejection fraction \< 40%
• Be willing to participate in cardiac rehabilitation, and not already done so in the last year
• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration
• Must be able to exercise on a treadmill

You may not qualify if:

• Inability to complete CPET or participate in CR (verbal/chart)
• Syncope during CPET within the last 6 mos, sustained VT on CPET, hemodynamically significant arrhythmia during CPET (verbal/chart)
• BMI \>= 38 (verbal/chart)
• History of a bleeding disorder or clotting abnormality (verbal/chart)
• Clinical diagnosis of severe Chronic Obstructive Pulmonary Disease (COPD) (verbal/chart)
• History of malignancy not considered in remission (verbal/chart)
• Cirrhosis (verbal/chart)
• Thyroid disease (verbal/chart)
• Thyroid Stimulating Hormone (TSH) value outside of the normal range for the laboratory within the last 1 year
• Individuals with hypothyroidism may be referred to their primary care provider (PCP) for evaluation and retested; any medication change must be stable for ≥3 months prior to retesting
• Individuals with hyperthyroidism are excluded, including those with normal TSH on pharmacologic treatment
• Cancer (verbal/chart)
• History of cancer treatment (other than non-melanoma skin cancer) and not "cancer-free" for at least 2 years
• Anti-hormonal therapy (e.g., for breast or prostate cancer) within the last 6 months
• Chronic active or latent infection (verbal/chart)

Sponsors & Collaborators

• Stanford University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• American Heart Association: collaborator

Study Sites (1)

Stanford Health Care

Stanford, California, 94305, United States

RECRUITING

Related Publications (2)

• Sanford JA, Nogiec CD, Lindholm ME, Adkins JN, Amar D, Dasari S, Drugan JK, Fernandez FM, Radom-Aizik S, Schenk S, Snyder MP, Tracy RP, Vanderboom P, Trappe S, Walsh MJ; Molecular Transducers of Physical Activity Consortium. Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise. Cell. 2020 Jun 25;181(7):1464-1474. doi: 10.1016/j.cell.2020.06.004.

  PMID: 32589957 BACKGROUND

• Contrepois K, Wu S, Moneghetti KJ, Hornburg D, Ahadi S, Tsai MS, Metwally AA, Wei E, Lee-McMullen B, Quijada JV, Chen S, Christle JW, Ellenberger M, Balliu B, Taylor S, Durrant MG, Knowles DA, Choudhry H, Ashland M, Bahmani A, Enslen B, Amsallem M, Kobayashi Y, Avina M, Perelman D, Schussler-Fiorenza Rose SM, Zhou W, Ashley EA, Montgomery SB, Chaib H, Haddad F, Snyder MP. Molecular Choreography of Acute Exercise. Cell. 2020 May 28;181(5):1112-1130.e16. doi: 10.1016/j.cell.2020.04.043.

  PMID: 32470399 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

Exercise; Cardiac Rehabilitation

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Daniel H Katz, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Investigator

Study Record Dates

• First Submitted: January 13, 2023
• First Posted: January 25, 2023
• Study Start: March 20, 2024
• Primary Completion (Estimated): May 26, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)