The Effect of Cardiac Rehabilitation on Ferroptosis in Patients With Coronary Artery Disease

NCT07722637 | Recruiting

• 2 other identifiers: 2025/489TTU-2025-15709
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Coronary artery disease (CAD) remains a major global health concern and is the leading cause of cardiovascular mortality worldwide. Cardiac rehabilitation (CR) is a comprehensive, evidence-based intervention that integrates exercise training with optimal medical management and has been shown to improve clinical outcomes in patients with CAD. The primary objective of this study is to investigate the effects of cardiac rehabilitation on ferroptosis, an iron-dependent form of regulated cell death, in patients with coronary artery disease. A total of 90 participants will be enrolled in the study after providing written informed consent. The study population will consist of three groups: 30 patients with CAD who participate in a cardiac rehabilitation program, 30 patients with CAD who voluntarily decline participation in cardiac rehabilitation, and 30 age- and sex-matched healthy volunteers without any known chronic disease. Peripheral venous blood samples will be collected from patients undergoing cardiac rehabilitation both before the initiation of the rehabilitation program and upon its completion. A single blood sample will be obtained from patients who decline participation in cardiac rehabilitation and from healthy control participants. To evaluate ferroptosis-related molecular alterations, the expression levels of the ferroptosis-associated genes GPX4, SLC7A11, ACSL4, FSP1, NRF2, TFRC, and NCOA4 will be analyzed. In addition, serum concentrations of ferroptosis-related biomarkers, including free iron, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and GPX4 protein, will be measured. The molecular and biochemical parameters will be compared among the three study groups, and changes in ferroptosis-related biomarkers before and after the cardiac rehabilitation program will be evaluated in patients undergoing cardiac rehabilitation.

Conditions

Coronary Artery Disease (CAD); Cardiac Rehab; Ferroptosis

Keywords

cardiac rehabilitation; ferroptosis; Coronary artery disease

Outcome Measures

Primary Outcomes (1)

• Change in GPX4 Gene Expression

  elative GPX4 gene expression in peripheral blood will be quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Changes in GPX4 gene expression before and after completion of the cardiac rehabilitation program will be evaluated in patients undergoing cardiac rehabilitation. Baseline GPX4 gene expression levels will also be compared among patients undergoing cardiac rehabilitation, patients who decline participation in cardiac rehabilitation, and healthy control participants.

  Baseline and immediately after completion of the cardiac rehabilitation program (6 weeks).

Secondary Outcomes (9)

• Change in SLC7A11 Gene Expression

  Baseline and immediately after completion of the cardiac rehabilitation program (6 weeks)

• Change in ACSL4 Gene Expression

  Baseline and immediately after completion of the cardiac rehabilitation program (6 weeks).

• Change in FSP1 Gene Expression

  Baseline and immediately after completion of the cardiac rehabilitation program (6 weeks).

• Change in NRF2 Gene Expression

  Baseline and immediately after completion of the cardiac rehabilitation program (6 weeks).

• Change in TFRC Gene Expression

  Baseline and immediately after completion of the cardiac rehabilitation program (6 weeks).

Study Arms (3)

Cardiac Rehabilitation Group

EXPERIMENTAL

Patients with coronary artery disease who will participate in a supervised cardiac rehabilitation program in addition to standard medical therapy. Peripheral venous blood samples will be collected before the initiation and after completion of the cardiac rehabilitation program for the assessment of ferroptosis-related gene expression and serum biomarkers.

Behavioral: Cardiac Rehabilitation

CAD Patients Declining Cardiac Rehabilitation

NO INTERVENTION

Patients with coronary artery disease who voluntarily decline participation in the cardiac rehabilitation program and continue to receive standard medical therapy. A single peripheral venous blood sample will be collected for the assessment of ferroptosis-related gene expression and serum biomarkers.

Healthy Control Group

NO INTERVENTION

Age- and sex-matched healthy volunteers without known cardiovascular or chronic diseases. A single peripheral venous blood sample will be collected for the assessment of ferroptosis-related gene expression and serum biomarkers.

Interventions

Cardiac Rehabilitation BEHAVIORAL

A supervised, comprehensive cardiac rehabilitation program consisting of individualized aerobic and resistance exercise training, patient education, lifestyle modification, and cardiovascular risk factor management according to current clinical practice guidelines.

Cardiac Rehabilitation Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients With Coronary Artery Disease (CAD):
• Age between 18 and 75 years.
• Diagnosis of coronary artery disease within the previous 3 months.
• Eligible to participate in a cardiac rehabilitation program or voluntarily decline participation in the cardiac rehabilitation program.
• Peak exercise capacity of ≥5 metabolic equivalents (METs).
• Able to undergo cardiopulmonary exercise testing (CPET).
• Able to understand the study procedures and provide written informed consent.
• Healthy Controls:
• Age between 18 and 75 years.
• No history of coronary artery disease or other cardiovascular diseases.
• No history of chronic systemic diseases, including diabetes mellitus, hypertension, chronic kidney disease, chronic liver disease, inflammatory or autoimmune diseases, or malignancy.
• Not receiving regular medication.
• Able to provide written informed consent.

You may not qualify if:

• Patients With Coronary Artery Disease (CAD):
• Decompensated heart failure.
• Unstable angina pectoris.
• Uncontrolled or complex ventricular arrhythmias.
• Severe pulmonary hypertension.
• Neurological, orthopedic, or musculoskeletal disorders limiting exercise performance.
• Absolute contraindications to cardiopulmonary exercise testing or cardiac rehabilitation according to current clinical guidelines.
• Chronic kidney failure or chronic liver disease.
• Active infection.
• Active inflammatory or autoimmune disease.
• Active malignancy or history of malignancy.
• Pregnancy.
• Cognitive or psychiatric disorders that would interfere with study participation or protocol compliance.
• Healthy Controls:
• History of coronary artery disease or other cardiovascular diseases.

Sponsors & Collaborators

• TC Erciyes University: lead

Study Sites (1)

Erciyes University Faculty of Medicine

Kayseri, Kayseri, 38039, Turkey (Türkiye)

RECRUITING

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MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Cardiac Rehabilitation

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Design

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

Model Details: Participants will be assigned to one of three parallel groups based on their clinical status and willingness to participate in a cardiac rehabilitation program. The first group will consist of patients with coronary artery disease (CAD) enrolled in a supervised cardiac rehabilitation program. The second group will include patients with CAD who voluntarily decline participation in cardiac rehabilitation and will receive standard medical care without rehabilitation. The third group will comprise age- and sex-matched healthy volunteers without known cardiovascular or chronic diseases. Blood samples will be collected before and after completion of the cardiac rehabilitation program in the rehabilitation group, whereas a single blood sample will be obtained from the non-rehabilitation and healthy control groups. Ferroptosis-related gene expression and serum biomarkers will be compared among the three groups, and pre- and post-rehabilitation changes will be evaluated in patients undergoing c

Study Record Dates

• First Submitted: July 19, 2026
• First Posted: July 23, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): November 15, 2026
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)