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NCT04906057

The Therapeutic Effects of Forced Aerobic Exercise in Multiple Sclerosis

Completed NA Results posted Last updated 6 March 2025
What this trial tests

NA trial testing Forced Aerobic Exercise (FE) in Multiple Sclerosis in 22 participants. Completed in 29 November 2022.

Timeline
6 July 2021
Primary endpoint
29 November 2022
29 November 2022

Quick facts

Lead sponsorThe Cleveland Clinic
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingsingle
Primary purposetreatment
Enrollment22
Start date6 July 2021
Primary completion29 November 2022
Estimated completion29 November 2022
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

The Cleveland Clinic

Who can join

Adults 18 to 75, any sex, with Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Exercise Duration Primary · collected during each exercise session (twice per week for 12 weeks)

Average exercise duration

GroupValue95% CI
Forced Aerobic Exercise (FE)42.2± 2.4
Voluntary Exercise (VE)42.2± 2.4
Aerobic Intensity Primary · Collected during each exercise session (twice per week for 12 weeks)

average percent max heart rate

GroupValue95% CI
Forced Aerobic Exercise (FE)0.63± 0.07
Voluntary Exercise (VE).70± 0.05
Exercise Cadence Primary · collected during each exercise session (twice per week for 12 weeks)

Average Exercise Cadence (cycling rate)

GroupValue95% CI
Forced Aerobic Exercise (FE)69.1± 11.1
Voluntary Exercise (VE)64.5± 16.7
Six Minute Walk Test Primary · Week 0 (baseline), Week 13 (post exercise sessions)

The distance walked over 6 minutes is measured on an oval walking track

Baseline
GroupValue95% CI
Forced Aerobic Exercise (FE)339.1± 123.3
Voluntary Exercise345.9± 110.7
EOT
GroupValue95% CI
Forced Aerobic Exercise (FE)338.3± 111.5
Voluntary Exercise373.6± 128.6
Gait Velocity Primary · Week 0 (baseline), Week 13 (post exercise sessions)

Spatio-temporal and kinematic parameters of gait will be obtained using 3-D motion capture and an instrumented walkway.

Zeno Velocity Self-Paced Baseline (average)
GroupValue95% CI
Forced Aerobic Exercise (FE)90.6± 17.3
Voluntary Exercise91.5± 30.6
Zeno Velocity Fast-Paced Baseline (average)
GroupValue95% CI
Forced Aerobic Exercise (FE)122.4± 19.3
Voluntary Exercise131.0± 13.0
CAREN Walking Speed Baseline (Average)
GroupValue95% CI
Forced Aerobic Exercise (FE)0.54± .28
Voluntary Exercise0.65± 0.30
PROMIS-29 Primary · Week 0 (baseline), Week 13 (post exercise sessions)

The Patient-Reported Outcomes Measurement Information System (PROMIS) is a set of person-centered measures that evaluates and monitors physical, mental, and social health in the general population and with individuals living with chronic conditions. Raw scores were converted to T-scores (using an adult referent population) ranging from 0-100 with a mean of 50 and standard deviation (SD) of 10 in the referent population. For the PROMIS-29 symptom-related domains (anxiety, depression, fatigue, sleep disturbance, and pain interference), higher scores represent greater symptom burden (worse functi

PROMIS Physical at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE) + Voluntary Exercise (VE)40.2± 7.8
Voluntary Exercise40.8± 7.8
PROMIS Physical at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE) + Voluntary Exercise (VE)40.0± 6.0
Voluntary Exercise40.0± 5.0
PROMIS Anxiety at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE) + Voluntary Exercise (VE)46.6± 7.6
Voluntary Exercise49.5± 12.3
PROMIS Anxiety at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE) + Voluntary Exercise (VE)45.8± 6.3
Voluntary Exercise45.6± 7.3
PROMIS Depression at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE) + Voluntary Exercise (VE)46.1± 7.8
Voluntary Exercise46.5± 10.8
PROMIS Depression at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE) + Voluntary Exercise (VE)45.7± 7.7
Voluntary Exercise45.8± 6.6
PROMIS Fatigue at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE) + Voluntary Exercise (VE)50.8± 11.5
Voluntary Exercise53.5± 5.2
PROMIS Fatigue at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE) + Voluntary Exercise (VE)48.6± 11.0
Voluntary Exercise47.9± 3.3
Modified Fatigue Impact Scale (MFIS) Primary · Week 0 (baseline), Week 13 (post exercise sessions)

The MFIS is a 21-item self-reported measure of how fatigue impacts the lives of persons with multiple sclerosis. This instrument provides an assessment of the effects of fatigue as it relates to physical, cognitive, and psychosocial functioning. Participants rate on a 5-point Likert scale, with 0 = 'Never' to 4 = 'Almost always' their agreement with 21 statements. Total score (0-84) and subscales for physical (0-36), cognitive (0-40) and psychosocial functioning (0-8). Higher numbers indicate greater fatigue in all domains.

MFIS total score at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE)21.9± 18.5
Voluntary Exercise33.4± 12.8
MFIS total score at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE)18.6± 18.7
Voluntary Exercise20.2± 7.5
MFIS Physical Subscale at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE)14.0± 10.6
Voluntary Exercise18.7± 6.9
MFIS Physical Subscale at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE)9.9± 10.3
Voluntary Exercise11.8± 3.6
MFIS Cognitive Subscale at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE)7.6± 7.4
Voluntary Exercise12.3± 7.3
MFIS Cognitive Subscale at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE)7.2± 6.9
Voluntary Exercise6.8± 6.6
MFIS Psychosocial Subscale at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE)2.0± 1.90
Voluntary Exercise2.3± 2.1
MFIS Psychosocial Subscale at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE)1.5± 1.7
Voluntary Exercise1.6± 1.7
Multiple Sclerosis Manual Dexterity Test Primary · Week 0 (baseline), Week 13 (post exercise sessions)

Assessment examining cognitive and hand function for persons with MS

Manual Dexterity Test (Right) at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE)31.4± 8.2
Voluntary Exercise (VE)24.3± 4.1
Manual Dexterity Test (right) at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE)32.4± 7.8
Voluntary Exercise (VE)23.9± 4.4
Manual Dexterity Test (Left) at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE)33.8± 5.8
Voluntary Exercise (VE)25.4± 2.0
Manual Dexterity Test (left) at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE)35.4± 9.8
Voluntary Exercise (VE)39.6± 35.9
Processing Speed Test Primary · Week 0 (baseline), Week 13 (post exercise sessions)

Assessment examining processing speed using an tablet-based measure developed to closely resemble the symbol digit modalities test. Participants match symbols to digits over a 2-minute trial. The number of correct matches represents the score, with higher correct matches indicative of better processing speed performance. The low range of possible scoring is 0 with no upper range limit. In a study by Rao and colleagues (2017), persons with MS scored and average of 51.1 (+/- 11.9) on the first trial and 52.8 (+/- 2.0) on the second trial. One trial was conducted in this study.

Processing speed test total correct at baseline
GroupValue95% CI
Forced Aerobic Exercise (FE)43.0± 8.0
Voluntary Exercise55.3± 8.5
Processing speed test total correct at EOT
GroupValue95% CI
Forced Aerobic Exercise (FE)45.1± 9.4
Voluntary Exercise57.4± 9.8
To Investigate the Role of Klotho in Promoting Neuroprotection. Secondary · Week 1 (exercise session 1), Week 12 (exercise session 24)

Laboratory Assessment: Blood draws will be conducted at 4 different points in time to determine the acute and long-term change in serum Klotho; at week one session one, pre- and post-exercise, and at the last session12-week exercise intervention, pre- and post-exercise.

Klotho (Baseline Pre-Exercise)
GroupValue95% CI
Forced Aerobic Exercise (FE)1273.3± 787.7
Voluntary Aerobic Exercise (VE)1100.4± 878.0
Klotho (Baseline Post-Exercise)
GroupValue95% CI
Forced Aerobic Exercise (FE)929.5± 661.1
Voluntary Aerobic Exercise (VE)1166.4± 745.4
Klotho (Final Session pre-exercise)
GroupValue95% CI
Forced Aerobic Exercise (FE)948.3± 550.2
Voluntary Aerobic Exercise (VE)1019.4± 608.7
Klotho (Final Session post-exercise)
GroupValue95% CI
Forced Aerobic Exercise (FE)1265.8± 940.2
Voluntary Aerobic Exercise (VE)154.4± 1104.1
Neurofilament light (Baseline)
GroupValue95% CI
Forced Aerobic Exercise (FE)14.6± 7.5
Voluntary Aerobic Exercise (VE)14.5± 7.3
Neurofilament light (Final Session)
GroupValue95% CI
Forced Aerobic Exercise (FE)16.5± 6.4
Voluntary Aerobic Exercise (VE)15.0± 4.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse experiences were collected up to 19 weeks from start to completion of the study.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Forced Aerobic Exercise (FE)
Serious: 1/12 (8%)
Deaths: 0/12
Voluntary Aerobic Exercise (VE)
Serious: 0/10 (0%)
Deaths: 0/10

Serious adverse events (1 terms)

ReactionSystemForced Aerobic Exercise (FE)Voluntary Aerobic Exercise…
STEMICardiac disorders
Other adverse events (2 terms — click to expand)

ReactionSystemForced Aerobic Exercise (FE)Voluntary Aerobic Exercise…
Covid-19 DiagnosisRespiratory, thoracic and mediastinal disorders
FallInjury, poisoning and procedural complications

Most-reported serious reactions: STEMI.

Data from ClinicalTrials.gov NCT04906057 adverse events section.

Sponsor's own description

This project will investigate the feasibility and initial efficacy of two aerobic exercise training approaches, forced and voluntary, to improve motor function in persons with multiple sclerosis (MS). We hypothesize that intensive aerobic exercise training elicits a neurorepairative and neurorestorative response on the central nervous system, which may improve motor function as it relates to gait and mobility. Should aerobic cycling, forced or voluntary, improve gait and functional mobility in persons with MS, it would serve as a new model to restoring function, rather than current models that focus on compensation.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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