Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626000145303
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
15/12/2025
Date registered
Help: Date registered
5/02/2026
Date last updated
Help: Date last updated
5/02/2026
Date data sharing statement initially provided
Help: Data sharing statement date
5/02/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
HIIT the Gym: The effects of High Intensity Interval Training (HIIT) on improving fatigue in Multiple Sclerosis
Scientific title
HIIT the Gym: The effects of High Intensity Interval Training (HIIT) on improving fatigue in Multiple Sclerosis – a metabolomics and microbial study
Additional trial identifiers [1] 304111 0
None
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
fatigue 321789 0
cognition 321791 0
depression 321792 0
Multiple Sclerosis 340286 0
Condition category
Condition code
Neurological 319518 319518 0 0
Multiple sclerosis
Mental Health 336750 336750 0 0
Depression
Mental Health 336751 336751 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
The intervention is High-Intensity Interval Training (HIIT) using stationary cycle ergometry conducted in people with multiple sclerosis. Participants are stratified into high-fatigue and low-fatigue groups based on age- and education-adjusted Modified Fatigue Impact Scale (MFIS) cut-off scores; however, all participants receive the same intervention protocol.

Materials required for the intervention include stationary cycle ergometers (Fluid E750 Cycle Body Trainer) and Polar H10 heart-rate monitors for continuous heart-rate monitoring.

The intervention procedure involves participants attending supervised HIIT cycling sessions for 8 weeks (two 30-minute sessions per week; 16 sessions total). Each session begins with a 5-minute warm-up at low intensity, followed by 10 repeated cycles of 90 seconds of high-intensity cycling and 30 seconds of moderate-intensity cycling for active recovery. Each session concludes with a 5-minute cool-down at low intensity.

The session structure, prescribed intensity zones, and cycling cadence are standardised across participants. High-intensity intervals target a Borg Rating of Perceived Exertion (RPE) of 15–19, corresponding to approximately 85–95% of age-predicted maximal heart rate (HRmax), while moderate-intensity intervals target an RPE of 12–14, corresponding to approximately 60–75% HRmax. Cycling cadence is standardised at approximately 80–100 revolutions per minute during high-intensity intervals and 60–80 revolutions per minute during moderate-intensity intervals. Cycling resistance is adjusted individually for each participant to achieve the target intensity.

Sessions are delivered face-to-face on a one-to-one basis by tertiary-qualified Exercise Physiologists with experience in neurological and multiple sclerosis rehabilitation. Absolute workload (e.g. cycling resistance) is individualised and adjusted within or between sessions by the Exercise Physiologist based on continuous heart-rate monitoring, RPE ratings, fatigue, and clinical presentation to safely maintain the intended relative intensity of the intervention. All sessions are conducted within an outpatient clinical setting in a rehabilitation gym located in Sydney, Australia.

Exercise intensity and intervention fidelity are monitored during each session using continuous heart-rate monitoring (Polar H10) and repeated RPE ratings recorded by the supervising Exercise Physiologist. Adherence is assessed as the proportion of prescribed sessions attended, calculated as the percentage of completed sessions out of the total 16 scheduled sessions. Any protocol deviations, intensity adjustments, or adverse events are documented in standardised session records.
Intervention code [1] 320442 0
Rehabilitation
Description of the comparator or control
Both high- and low-fatigue groups will complete the same HIIT intervention, with the low-fatigue group serving as the control/comparator group.
Control group
Active

Outcomes
Primary outcome [1] 327385 0
Mean Modified Fatigue Impact Scale Score
Timepoint [1] 327385 0
This outcome is collected all timepoints including baseline (1-week before the intervention) and at 1 & 4-weeks post intervention. The primary endpoint is at 1-week post intervention.
Primary outcome [2] 327386 0
Mean Visual Analogue Scale for Fatigue Severity - Fatigue subscale score
Timepoint [2] 327386 0
This outcome is collected all timepoints including baseline (1-week before the intervention) and at 1 & 4-weeks post intervention. The primary endpoint is at 1-week post intervention.
Primary outcome [3] 327387 0
Sustained Attention through the Mean change in the The Conners Continuous Performance Test-III Score
Timepoint [3] 327387 0
This outcome is collected all timepoints including baseline (1-week before the intervention) and at 1 & 4-weeks post intervention. The primary endpoint is at 1-week post intervention.
Secondary outcome [1] 455899 0
Change in time use spent in light activities measured through AX3 Accelerometry data collection
Timepoint [1] 455899 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [2] 455900 0
Change in Kynurenine Pathway Activation through a composite outcome in blood (Kynurenine to Tryptophan Ratio)
Timepoint [2] 455900 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [3] 455901 0
Change in gut microbiota diversity through faecal sample collection
Timepoint [3] 455901 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [4] 455902 0
Psychological state through Hospital Anxiety and Depression Scale
Timepoint [4] 455902 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [5] 455903 0
Dietary Habits through the Short Form Food Frequency Questionnaire
Timepoint [5] 455903 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [6] 455904 0
Sleep Quality assessed through the Pittsburgh Sleep Quality Index
Timepoint [6] 455904 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [7] 455905 0
Daytime somnolence through The Epworth Sleepiness Scale
Timepoint [7] 455905 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [8] 455906 0
self-reported physical activity with the Physical Activity Scale for Individuals with Physical Disabilities
Timepoint [8] 455906 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [9] 455907 0
Subjective cognition through the Perceived Deficits Questionnaire
Timepoint [9] 455907 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [10] 455908 0
Change in Paced Auditory Serial Addition Task performance (total score).
Timepoint [10] 455908 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [11] 456381 0
Mean Visual Analogue Scale for Fatigue Severity - Energy subscale score
Timepoint [11] 456381 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [12] 457004 0
Change in time use spent in moderate activities measured through AX3 Accelerometry data collection
Timepoint [12] 457004 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [13] 457005 0
Change in time use spent in vigorous activities measured through AX3 Accelerometry data collection
Timepoint [13] 457005 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [14] 457006 0
Change in Kynurenine Pathway Activation in urine through a composite outcome (Kynurenine to Tryptophan ratio)
Timepoint [14] 457006 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [15] 457007 0
Change in Kynurenine Pathway Metabolism in blood through a composite outcome (Kynureninic Acid to Quinolinic Acid ratio)
Timepoint [15] 457007 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [16] 457008 0
Change in Kynurenine Pathway Metabolism in urine through a composite outcome (Kynureninic Acid to Quinolinic Acid ratio)
Timepoint [16] 457008 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [17] 457277 0
Change in Symbol Digits Modality Task performance (total score)
Timepoint [17] 457277 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [18] 457278 0
Change in Selective Reminding Test performance (total score)
Timepoint [18] 457278 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [19] 457279 0
Change in Trail Making Test performance (total time score)
Timepoint [19] 457279 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention
Secondary outcome [20] 457280 0
Change in performance on the Controlled Oral Word Association Test (total score)
Timepoint [20] 457280 0
Baseline (1-week before the intervention) and at 1 & 4-weeks Post Intervention

Eligibility
Key inclusion criteria
people with a formal diagnosis of relapsing-remitting multiple sclerosis (RRMS) by a clinician, aged 18–50 years, with mild to moderate disability (EDSS score of 2-6). These criteria represent the largest proportion of individuals living with MS.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
Cardiovascular/neurological disorders (e.g. strokes, epilepsy, brain injury), substance abuse or other health complications, involved in physical therapy treatment at the time of recruitment, acute exacerbation of symptoms 4 weeks prior to assessment, diagnosis of psychotic, bipolar or related disorder and use of DMD: corticosteroid use in the last 4 weeks or immune-suppressive therapy in the last 6 months.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2026
Actual
Date of last participant enrolment
Anticipated
1/04/2028
Actual
Date of last data collection
Anticipated
1/06/2028
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 308492 0
University
Name [1] 308492 0
Macquarie University
Country [1] 308492 0
Australia
Primary sponsor type
University
Name
Macquarie University
Address
Country
Australia
Secondary sponsor category [1] 323431 0
Commercial sector/Industry
Name [1] 323431 0
Ms Plus
Address [1] 323431 0
Country [1] 323431 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308449 0
Macquarie University Human Research Ethics Committee Medical Sciences
Ethics committee address [1] 308449 0
Ethics committee country [1] 308449 0
Australia
Date submitted for ethics approval [1] 308449 0
03/11/2022
Approval date [1] 308449 0
01/12/2023
Ethics approval number [1] 308449 0
520241262859832

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110738 0
Miss Lorraine Sue Ying Tan
Address 110738 0
4 First Walk, School of Psychological Science, Faculty of Medicine, Health and Human Sciences Level 3 North, AHH, Macquarie University, NSW 2109, Australia
Country 110738 0
Australia
Phone 110738 0
+61401782007
Fax 110738 0
Email 110738 0
[email protected]
Contact person for public queries
Name 110739 0
Lorraine Sue Ying Tan
Address 110739 0
4 First Walk, School of Psychological Science, Faculty of Medicine, Health and Human Sciences Level 3 North, AHH, Macquarie University, NSW 2109, Australia
Country 110739 0
Australia
Phone 110739 0
+61401782007
Fax 110739 0
Email 110739 0
[email protected]
Contact person for scientific queries
Name 110740 0
Lorraine Sue Ying Tan
Address 110740 0
4 First Walk, School of Psychological Science, Faculty of Medicine, Health and Human Sciences Level 3 North, AHH, Macquarie University, NSW 2109, Australia
Country 110740 0
Australia
Phone 110740 0
+61401782007
Fax 110740 0
Email 110740 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• No requirements
What individual participant data might be shared?
• De-identified individual participant data:
• Primary outcome(s)
• Safety data
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Health economic analyses
• Studies testing whether findings can be repeated or confirmed
• Teaching research methods or developing new statistical techniques
When can requests for individual participant data be made (start and end dates)?
From:
At the end of the study
To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Data repository: Macquarie Research Data Repository

• Email of trial custodian, sponsor or committee: [email protected]

Are there extra considerations when requesting access to individual participant data?
Yes: institutional policies on data sharing, the request must also come with ethics approval for the proposed data analysis/study



What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol    HREA-Project-Description - RCT_V3_Clean.pdf
Ethical approval    attachmentEntry-108280 (2).pdf
Informed consent form    HIIT_PICF_V3_Clean.pdf


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.