Effects of HIIT on HRV in Sub-acute Post-stroke Patients (E(AVC))

December 26, 2025 updated by: Benjamin BERNUZ, MD, Hôpital Léon Bérard

Effect of a High-intensity Interval-training on "Heart Rate Variability" Prognostic Parameters in Early Post-stroke Patients: A Randomized Controlled Trial

Objective. To assess the effect of innovative "High-Intensity Interval Training" (HIIT) on Heart Rate Variability, a strong biomarker of positive outcome after stroke.

Design. A randomized controlled study with blinded assessment of the main criteria.

Population. NIHSS<20 post-stroke patients, hospitalized in secondary care stroke-units within the first 3 months (sub-acute phase).

Selection. Eligibility test on a semi-recumbent cycloergometer Intervention. In addition to a standard neurorehabilitation program (3±1 sessions daily, including cognitive and occupational therapy, physiotherapy with strengthening-stretching exercises), the aerobic group will benefit from a HIIT procedure (HIIT group) with a semi-recumbent cycloergometer, for 6 weeks representing 16 sessions; while the non-aerobic group will undertake a "Low-Intensity Group-Gymnastic Training" (Control or LIGT Group) (=segmental strengthening-stretching and proprioceptive exercises mainly), with the same training volume and frequency for both groups.

Main outcome measure. Standard Deviation of Normal-to-Normal RR intervals (SDNN) from 24h Holter-ECG recordings at W4, W8 and M6.

Modifications in patients' medical management are expected, as generalization of AT in moderate to severe stroke patients at the sub-acute phase, with "Low volume HIIT" and simple devices.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

A randomized controlled 2-arms parallel study, comparing HRV in two groups of stroke patients.

Post-acute stroke patients hospitalized in rehabilitation stroke¬-units, within secondary care hospitals, are screened for eligibility.

  • Inclusion criteria:

    • first-ever hemispheric stroke, with consistent clinical and neuroimaging signs
    • <3 month
    • NIHSS <20 in acute care
    • age>18

  • Non-inclusion criteria:

    • complicated diabetes mellitus with objective neuropathy and/or autonomic dysfunction
    • other concomitant cardiac or pulmonary diseases possibly affecting HRV recordings, ie: acute myocardial infarction (<6 month), myocardial dysfunction as severe dilated or hypertrophic cardiomyopathy, class 3 and 4 heart failure, arrhythmias including chronic atrial fibrillation, conduction abnormalities.
    • beta-blockers with no alternative options
    • severe cognitive impairment inconsistent with free, informed and written consent or questionnaire filling
  • Patients will benefit beforehand from a symptom-limited Graded Exercise Test (GXT), with ECG monitoring and using a semi recumbent cycle ergometer (Ergoline, Optibike MED600), mainly to exclude a CV risk and to accurately assess their exercise capacities for better individualized programs. Peak oxygen uptake, Peak Power , Peak Heart Rate, Respiratory Exchange Ratio (VO2peak, Power peak, HRpeak, RER respectively) will be measured, Ventilatory Threshold 1 (VT1) will be estimated, and oxygen uptake, power and heart rate at VT1 will be recorded (VO2vt1, Pvt1, HRvt1).
  • The standard-of-care neuro-rehabilitation program was carried out according to the international recommendations. It will consist daily in a mean of 3 sessions (2 to 4), five days a week: physiotherapy (with, among others, Strengthening-Stretching activity), occupational therapy, cognitive therapy (orthophonist or neuro-psychologist).

In addition, either aerobic training (HIIT) or non-aerobic training (Control Group-CG by Low Intensity Group Training-LIGT).

  • HIIT and LIGT training volume and duration will be the same (16 sessions, 12 to 30' each, 6 weeks).

The intervention-group (HIIT Group) will realize a 6-weeks Aerobic Training as follows:

Among the FITT principle:

  • Frequency: 2-3 times a week

  • Intensity: long-HIIT: 4 to 5 four-minutes intervals at Pvt1(+/- 2 steps) interspersed with two-minutes interval at 50% Pvt1=(4-5 x (4':2')/(Pvt1 :50%Pvt1))

    • short-HIIT: 8 to 10 forty-five seconds intervals at Pmax (+/- 2 steps) interspersed with forty-five seconds rest intervals = (8-10x(45":45")/Pmax :Rest))
  • Time: 12' to 30' per session (8 short-sessions of 12 to 15', 8 long-sessions of 24 to 30')
  • Type: cycling on a semirecumbent ergometer Depending on the patient's fatigue and progress, the intensity will be adjusted, with an HR target >80% HRpeak during intervals.

In the CG group, HIIT will be replaced by "LIGT" sessions, as follows:

Among the FITT principle:

  • Frequency: 2-3 times a week
  • Intensity: Low HR controlled by HR monitoring (<50% HRpeak or 30%HRR)
  • Time: 12' to 30' per session (8 short-sessions of 12 to 15', 8 long-sessions of 24 to 30')

  • Type: Static and Segmental strengthening and stretching mainly

    • Measures taken to reduce bias:

      -Patients' spontaneous physical activity will be monitored via two sets of four-day measurements, including weekends, using an Actigraph device worn on a belt.

      • The primary endpoint will always be measured over 24 hours, at the same time of week; it will be read blind by the same cardiologist (single-blind).
      • Known criteria for HRV modification will be monitored (side of the lesion, fever, blood pressure spike or hypoxia during measurement, medication intake).
      • The other criteria will always be measured during the same half-day.
      • In order to introduce a "blind component" for the patient (double-blind), the information provided to the patient will specify a "comparison between two different types of physical activity "
    • At M6, only the primary endpoint will be measured. A Marshall questionnaire will be used at this time to verify the proportion of patients complying with WHO recommendations on physical activity at 6 months post-discharge.

Patients who would have been in the control-group will be proposed to enter in an out-patient (day-hospital) HIIT program.

  • Novelty

    1. To use a new and strong risk marker of stroke relapse and post-stroke complications (mortality, morbidity, and poor functional outcomes), which is improved by physical activity, to strengthen the use of Aerobic Training (AT) in secondary prevention.

    2. To allow generalization of conclusions:

      • by studying AT with a shorter intervention-design, limiting competition with neuro-rehabilitation (fatigue, time spent) and via a simple intervention-device (semi recumbent ergometer).

      (Indeed, most of non-ambulatory participants (82% ) in RCTs benefited from AT through assistive walking devices, using Weight Bearing Support Treadmill, which are difficult to set up (accessibility, personnel and equipment costs…)).

      • by studying AT effects in a more disabled population and at an early stage. (Indeed, in Randomized Controlled Studies having assessed AT in chronic (>6months) post-stroke patients, NIHSS ≤ 5/42 was most often chosen for inclusion criterion, with a median NIHSS around 3 at study start.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • 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

  • France
    • PACA
      • Hyères, PACA, France, 83418
        • Dr BARTHOLOMEI MN

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • first-ever hemispheric stroke, with consistent clinical and neuroimaging signs
  • <3 month
  • NIHSS <20 in acute care

Exclusion Criteria:

  • age<18 years-old
  • diabetes mellitus complicated by neuropathy or autonomic dysfunction; or any other concomitant nervous system, cardiac or pulmonary disease possibly affecting the autonomic nervous system ie:
  • myocardial infarction< 6 months,
  • myocardial dysfunction as severe dilated or hypertrophic cardiomyopathy, class 3 and 4 heart failure,
  • severe conduction abnormalities and arrhythmias, including chronic atrial fibrillation,
  • mechanical ventilation,
  • beta-blockers with no alternative options, pharmacological mandatory treatment possibly affecting the autonomic nervous system and HRV.
  • severe cognitive impairment inconsistent with free, informed and written consent or questionnaire filling

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High Intensity Interval Training (HIIT)
HIIT 16 sessions of 12 to 30 minutes, over 6 weeks.
Other: HIIT
High Intensity Interval Training On semi-recumbent ergocyclometer, after a symptom-limited graded exercise Test
Placebo Comparator: Low Intensity Group Training (LIGT)
LIGT 16 sessions of 12 to 30 minutes, over 6 weeks.
Other: LIGT
Low Intensity Group Training Group gymnastics, mainly with short static stretching/strengthening tasks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SDNN
Time Frame: Week 1, Week 8, Month 6
Standard Deviation of all Normal-to-Normal RR intervals, recorded with a 24h-Holter ECG.
Week 1, Week 8, Month 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HRV
Time Frame: Week 1, Week 8, Month 6
Others data from the Heart Rate Variability analysis
Week 1, Week 8, Month 6
Dose Ratio
Time Frame: Week 2 to Week 7
Delivered/Planned ratio, as Internal Acceptability
Week 2 to Week 7
VO2peak
Time Frame: Week1 Vs Week 8
VO2peak gain between the first and second CPET will be compared
Week1 Vs Week 8

Collaborators and Investigators

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

Sponsor

Hôpital Léon Bérard

Collaborators

Fondation de l'Avenir

Investigators

  • Study Chair: Olivier Gavarry, Toulon University, STAPS Faculty

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

Helpful Links

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)

March 15, 2024

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

October 30, 2023

First Submitted That Met QC Criteria

November 9, 2023

First Posted (Actual)

November 15, 2023

Study Record Updates

Last Update Posted (Actual)

December 31, 2025

Last Update Submitted That Met QC Criteria

December 26, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-E(AVC)-V2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be available upon reasonable request. De-identified participant data will be available, from all types, for corresponding relevant Editor, or Meta-analyses need. Other detailed request will be examined.

Via controlled access repositories

IPD Sharing Time Frame

As soon as leading article is first published

IPD Sharing Access Criteria

Corresponding relevant Editor or Meta-analyses needs. Other detailed request will be examined.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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