Identifying Markers of Exercise Training in Heart Failure

February 11, 2026 updated by: Daniel Katz, Stanford University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Locations

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

    • Active or latent infections requiring chronic antibiotic or anti-viral treatment
    • Chronic active infection whether on chronic antimicrobials or not
    • Human Immunodeficiency Virus
    • Active hepatitis B or C undergoing antiviral therapy
    • Individuals successfully treated for hepatitis C and virologically negative for at least 6 months are not excluded

  • Tobacco (verbal/chart)

    • Current smokers: any tobacco or e-cigarette/e-nicotine products
    • Former smokers: Stopped smoking <6 months at time of screening
  • Not be pregnant or lactating in the last 12 months, or planning to become pregnant for the next 4 months. Not be post-partum during the last 12 months. (verbal/chart)
  • Metabolic bone disease (self-report): History of non-traumatic fracture from a standing height or less. Current pharmacologic treatment for low bone mass or osteoporosis, other than calcium, vitamin D, or estrogen. (verbal/chart)
  • Diabetes (self-report and screening), which includes: i) treatment with any insulin or ii) A1c >=8.0 (screening). (verbal/chart)
  • Chronic renal insufficiency (screening): estimated glomerular filtration rate <30 mL/min/1.73 m2 from serum creatinine (mg/dL) by the Chronic Kidney Disease Epidemiology Collaboration equation. (verbal/chart)
  • Individuals receiving any active treatment for autoimmune disorders (including monoclonal antibodies) within the last 6 months. (verbal/chart)
  • Alcohol consumption: i) more than 7 drinks per week for women and more than 14 drinks per week for men; ii) history of binge drinking. (verbal/chart)
  • Any individual engaging in night shift work in the last 6 months.
  • Hospitalization for any psychiatric condition within one year (verbal/chart)
  • 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. (verbal/chart)
  • Mental incapacity and/or cognitive impairment on the part of the participant that would inhibit adequate understanding of or cooperation with the study protocol

  • Other (clinician judgment)

    • Genetic metabolic disorders that could affect metabolomic results (e.g., phenylketonuria)
    • Any other cardiovascular, pulmonary, orthopedic, neurologic, psychiatric, metabolic, or other conditions that, in the opinion of the local clinician, would preclude participation and successful completion of the protocol
    • Any other illnesses that, in the opinion of the local clinician, would negatively impact or mitigate participation in and completion of the protocol

  • Medication exclusions (chart review)

    • Androgenic anabolic steroids, antiestrogens, antiandrogens
    • Growth hormone, insulin like growth factor, growth hormone releasing hormone
    • Insulin of any type used regularly
    • Any drugs used specifically to induce muscle growth/hypertrophy or augment exercise induced muscle hypertrophy

    • Psychiatric

      • Chronic use of medium- or long-acting sedatives and hypnotics, including all benzodiazepines; short-acting non-benzodiazepine sedative-hypnotics are allowed
      • Two or more drugs for depression
      • Mood stabilizers
      • Antiepileptic drugs
      • Stimulants, Attention-Deficit/Hyperactivity Disorder (ADHD) drugs
      • Anti-psychotic drugs
    • Narcotics and narcotic receptor agonists
    • Chronic systemic antimicrobials (antibiotic, antiviral, antifungal, antiparasite, etc) for any reason
    • High-potency topical steroids if ≥10% of surface area using rule of 9s
    • Continuous/chronic use of antibiotics or other anti-infectives for treatment or prevention
    • Monoclonal antibodies
    • Anti-rejection medications/immune suppressants
    • Any other medications that, in the opinion of local clinicians, would negatively impact or mitigate full participation and completion.

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: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Active arm: Acute exercise
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
40 minute moderate intensity exercise bout on a treadmill. This is similar to a single session of cardiac rehabilitation.
No Intervention: Control arm: No exercise (Acute Comparison)
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.
Experimental: Active Arm: 12 weeks Cardiac Rehabilitation
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
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.
No Intervention: Control: No Exercise (Training)
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Proteomic Profile: Chronic
Time Frame: Baseline vs week 12 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
Change in Proteomic Profile: Acute
Time Frame: Acute bout vs control; Baseline vs week 12 proteomic profile of acute exercise
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proteomic predictors of Cardiopulmonary fitness
Time Frame: Baseline vs week 12 proteomic profile
Participants will have cardiopulmonary exercise testing at baseline and after 12 weeks to assess the effects of cardiac rehab. The association between cardiopulmonary fitness metrics and proteomic profile will be assessed
Baseline vs week 12 proteomic profile

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Stanford University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
American Heart Association

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daniel H Katz, MD, Stanford University

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 20, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 26, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 13, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 13, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 25, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 68827
  • 23CDA1040581 (Other Grant/Funding Number: American Heart Association)
  • 5K23HL164980-02 (U.S. NIH Grant/Contract)

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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