Aerobic Exercise-induced Effect on Endothelial Function in Patients With Ischaemic Heart Disease
ENDO-R
Effect of Different Aerobic Exercise Methods in Cardiac Rehabilitation on Endothelial Function in Patients With Ischaemic Heart Disease and Study of the Associated Physiological Mechanisms (ENDO-R)
2 other identifiers
interventional
132
1 country
2
Brief Summary
Endothelial dysfunction is one of the aetiological factors in ischaemic heart disease (IHD). Aerobic exercise is effective in improving endothelial function, as measured by flow-mediated dilation (FMD), in patients with IHD. Within the aerobic exercise methods, there is evidence showing that high-intensity interval training (HIIT) increases FMD to a greater extent than moderate-intensity training (MIT) in these patients. Notably, in a recent review, our research group found that only studies performing long bouts of HIIT (long HIIT: higher than 1 min) found a greater effect on FMD, while no differences were found in those studies using short bouts of HIIT (short HIIT: ≤ 1 min) and MIT. However, no experimental studies comparing the effect of long HIIT, short HIIT, and MIT on endothelial function, as well as other predictors of mortality, such as cardiorespiratory fitness, brain-derived neurotrophic factor (BDNF) levels or parasympathetic branch activity, have been performed. Therefore, the main objective of this project will be to compare the effect of the three aerobic exercise methods on endothelial function, as measured by FMD, in patients with IHD. Complementarily, the effect of aerobic exercise, depending on the exercise method, on different mortality predictors will be compared. For this purpose, a multicentre randomised study will be carried out (2 hospitals in Elche and one in Alicante). Assessors will be blinded to the patients allocation. Participants will be aware about their allocation in the experimental groups due to the nature of the study. A total of 132 men and women with IHD (66 per sex), diagnosed between three and 12 months before the start of the intervention, aged between 45 and 75 years, and without limitations for the practice of exercise training, will be recruited. All patients will train 3 days a week for 12 weeks. Participants will be assessed before the intervention (i.e., pre), at 6 weeks of training (i.e., mid) and after the intervention (i.e., post). Physiological and psychological variables will be registered in the assessment periods. Training intensity will be individually prescribed based on the cardiopulmonary exercise test (CPET). Intensity exercise will be adapted after the first part of the intervention. Analysis of covariance will be used to compare the values of the three groups after the intervention for the continuous variables, including the pre-intervention value as a covariate, while a logistic regression model will be used for the categorical variables.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Nov 2024
Typical duration for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2024
CompletedFirst Submitted
Initial submission to the registry
January 15, 2025
CompletedFirst Posted
Study publicly available on registry
January 23, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 1, 2027
February 27, 2026
February 1, 2026
2.5 years
January 15, 2025
February 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (12)
Change from baseline in endothelial function at 7 weeks
Endothelial function (i.e., endothelial-dependent dilation) will be assessed by brachial FMD.
7 weeks
Change from baseline in endothelial function at 14 weeks
Endothelial function (i.e., endothelial-dependent dilation) will be assessed by brachial FMD.
14 weeks
Change from baseline in endothelial-independent dilation at 7 weeks
Brachial NMD will be used to measure endothelial-independent dilation.
7 weeks
Change from baseline in endothelial-independent dilation at 14 weeks
Brachial NMD will be used to measure endothelial-independent dilation.
14 weeks
Change from baseline in peak cardiopulmonary parameters at 7 weeks
Participants will perform a symptom-limited CPET on a cycle ergometer.
7 weeks
Change from baseline in peak cardiopulmonary parameters at 14 weeks
Participants will perform a symptom-limited CPET on a cycle ergometer.
14 weeks
Change from baseline in aerobic efficiency at 7 weeks
Efficiency-related variables will be measured during the CPET.
7 weeks
Change from baseline in aerobic efficiency at 14 weeks
Efficiency-related variables will be measured during the CPET.
14 weeks
Change from baseline in resting serum BDNF concentration at 7 weeks
Blood samples will be obtained through an indwelling catheter placed in the antecubital vein before the CPET.
7 weeks
Change from baseline in resting serum BDNF concentration at 14 weeks
Blood samples will be obtained through an indwelling catheter placed in the antecubital vein before the CPET.
14 weeks
Change from baseline in exercise-induced effect on serum BDNF at 7 weeks
Blood samples will be obtained through an indwelling catheter placed in the antecubital vein before and after the CPET.
7 weeks
Change from baseline in exercise-induced effect on serum BDNF at 14 weeks
Blood samples will be obtained through an indwelling catheter placed in the antecubital vein before and after the CPET.
14 weeks
Secondary Outcomes (12)
Change from baseline in pulmonary function at 7 and 14 weeks
7 and 14 weeks
Change from baseline in resting cardiopulmonary parameters at 7 and 14 weeks
7 and 14 weeks
Change from baseline in cardiopulmonary parameters at first and second ventilatory thresholds at 7 and 14 weeks
7 and 14 weeks
Change from baseline in cardiopulmonary variables measured during the recovery at 7 and 14 weeks.
7 and 14 weeks
Change from baseline in MacNew domains at 7 and 14 weeks
7 and 14 weeks
- +7 more secondary outcomes
Study Arms (3)
Moderate-intensity training (MIT) group
EXPERIMENTALContinuous exercise training on a cycle ergometer
Short high-intensity interval training (HIIT) group
EXPERIMENTALHigh-intensity interval exercise performed on a cycle ergometer
Long high-intensity interval training (HIIT) group
EXPERIMENTALHigh-intensity interval exercise performed on a cycle ergometer
Interventions
Patients allocated to the MIT group will train on a cycle ergometer three days a week for 12 weeks (36 sessions). They will cycle continuously between the first and second ventilatory thresholds. The duration of each exercise session will be set according to the estimated energy expenditure of the long HIIT and short HIIT groups for each training block (energy expenditure-adjusted exercise sessions). All sessions will be supervised, and patients will be asked to avoid additional exercise. They will be allowed to perform extra physical activity (e.g., light walking) according to medical recommendations.
Patients allocated to the Short HIIT group will train on a cycle ergometer three days a week for 12 weeks (36 sessions). They will perform from two to four 4-repetition sets of 1-min above the second ventilatory threshold. Patients will perform 1- and 3-min active recovery periods below the first ventilatory threshold between repetitions and sets, respectively. The total time spent at high intensity will range from eight to 16 min. All sessions will be supervised, and patients will be asked to avoid additional exercise training. They will be allowed to perform extra physical activity (e.g., light walking) according to medical recommendations.
Patients allocated to the Long HIIT will train on a cycle ergometer three days a week for 12 weeks (36 sessions). They will perform from two to four 4-min high-intensity exercise bouts above the second ventilatory threshold separated by 4-min active recovery periods below the first ventilatory threshold. The total time spent at high intensity will range from eight to 16 min. All sessions will be supervised, and patients will be asked to avoid additional exercise training. They will be allowed to perform extra physical activity (e.g., light walking) according to medical recommendations.
Eligibility Criteria
You may qualify if:
- Men and women aged between 45 and 75 years.
- Diagnosed with acute myocardial infarction, unstable or stable angina.
- Treated with percutaneous coronary intervention, coronary artery bypass grafting, or conservative treatment.
- Event or intervention within 3 to 12 months prior to participation in the study.
- Fluency in speaking and reading Spanish.
- Residing in Elche or surrounding areas and able to attend evaluations and the exercise programme (not planning to be absent for more than one week during the programme).
- Functional Class I-II according to the New York Heart Association (NYHA) classification.
- No physical limitations for exercise.
- Stable optimal medical treatment.
You may not qualify if:
- Use of walking assistive devices.
- Treatment with chemotherapy for any type of cancer in the past 2 years.
- Hospitalisation in an intensive care unit in the past 6 months for reasons other than the ischaemic event.
- Acute myocardial infarction group IV Killip-Kimball.
- Obesity grade III (≥40.0 kg/m²).
- Diabetes with uncontrolled blood glucose levels.
- Poorly controlled hypertension: resting blood pressure \> 180/110 mmHg.
- Chest pain with exertion or ST-segment changes suggestive of residual ischemia during ergometry. Residual ischemia.
- Severely reduced functional capacity on initial ergometry (\<5 metabolic equivalent of task).
- Left ventricular ejection fraction less than 50%.
- Severe stenosis of the left main coronary artery (\>50% significant disease).
- Severe aortic stenosis, left ventricular outflow tract obstruction (e.g., obstructive hypertrophic cardiomyopathy) or aortic dissection.
- Severe valvulopathy.
- Acute pulmonary embolism or deep vein thrombosis.
- Severe pulmonary hypertension.
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Instituto de Investigación Sanitaria y Biomédica de Alicante
Alicante, Alicante, 03010, Spain
Centro de Investigación del deporte
Elche, Alicante, 03202, Spain
Related Publications (1)
Fuertes-Kenneally L, Blasco-Peris C, Casanova-Lizon A, Baladzhaeva S, Climent V, Sarabia JM, Manresa-Rocamora A. Effects of high-intensity interval training on vascular function in patients with cardiovascular disease: a systematic review and meta-analysis. Front Physiol. 2023 Jul 27;14:1196665. doi: 10.3389/fphys.2023.1196665. eCollection 2023.
PMID: 37576344BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- An external researcher will conduct central allocation
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 15, 2025
First Posted
January 23, 2025
Study Start
November 1, 2024
Primary Completion (Estimated)
May 1, 2027
Study Completion (Estimated)
November 1, 2027
Last Updated
February 27, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- From November 2027 to November 2030
The Instituto de Investigacion Sanitaria y Biomedica de Alicante (ISABIAL) Community in ZENODO. Depositing in ZENODO allows selecting the type of access for each file (open, embargoed; restricted; closed) and the license for use (Creative Commons Attribution 4.0 International, which requires citing the database and the original study, as well as mentioning any changes made; this is suggested at the institutional level for files identified with open access). It is important to note that the use of ZENODO is temporary, until it is viable to use the REPISALUD repository, from the Carlos III Health Institute, by the ISABIAL research community. At least two different files will be included: i) The one corresponding to the data set; ii) One or more files with complementary information about the characteristics of the variables and/or study metadata (project, authors, related publication, keywords, etc.).