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IRCT20241205063953N6 IRCT 2026-08-01 Islamic Azad University Effect of Different Doses of Combined Aerobic-Resistance Exercise on Neuroaxonal Injury and Clinical Outcomes in Patients With Multiple Sclerosis Comparison of the Effects of Different Doses of Combined Aerobic-Resistance Exercise on Neuroaxonal Injury and Clinical Outcomes in Patients With Relapsing-Remitting Multiple Sclerosis 2026-08-01 anticipated 120 Complete https://irct.ir/trial/91706 interventional Randomization: Randomized, Blinding: Single blinded, Placebo: Not used, Assignment: Parallel, Purpose: Supportive, Other design features: This study is a three-arm randomized controlled trial with blinded outcome assessment investigating the effects of different doses of combined aerobic-resistance exercise on a neuroaxonal injury biomarker (sNfL) and clinical outcomes in patients with multiple sclerosis, Randomization description: Eligible participants will be randomly allocated in a 1:1:1 ratio to low-dose, moderate-dose, or high-dose exercise groups after completion of baseline assessments. Individual randomization will be performed using variable block randomization. Stratified randomization will be applied according to sex (female/male) and baseline disability level based on the Expanded Disability Status Scale (EDSS ≤3.5 and >3.5) to minimize potential confounding effects. The random allocation sequence will be generated by an independent researcher using statistical software. Group allocation will be concealed using sequentially numbered, opaque, sealed envelopes prepared by a researcher who is not involved in participant recruitment or intervention delivery, Blinding description: Participants and exercise trainers will not be blinded due to the nature of the exercise intervention. The principal investigator and intervention staff will be aware of group allocation. However, outcome assessors, laboratory personnel responsible for biomarker analyses, and the statistician will remain blinded to treatment allocation. Biological samples will be analyzed using coded identifiers, and group assignments will remain concealed until completion of the primary statistical analysis. N/A Condition 1: Relapsing-remitting multiple sclerosis (RRMS). Condition 2: Multiple sclerosis. Intervention 1: Intervention Low-dose Combined Aerobic-Resistance Exercise group: Participants will complete a 16-week combined aerobic-resistance exercise program. Training will be performed three sessions per week. Aerobic exercise will be prescribed at 50–60% of heart rate reserve, and resistance exercise will be performed at 50–60% of one-repetition maximum. Each session will include warm-up, aerobic training, resistance training, and cool-down. Intervention 2: Intervention moderate-dose Combined Aerobic-Resistance Exercise group: Participants will complete a 16-week combined aerobic-resistance exercise program. Training will be performed three sessions per week. Aerobic exercise will be prescribed at 65–75% of heart rate reserve, and resistance exercise will be performed at 60–70% of one-repetition maximum. Each session will include warm-up, aerobic training, resistance training, and cool-down. Intervention 3: Intervention high-dose Combined Aerobic-Resistance Exercise group: Participants will complete a 16-week combined aerobic-resistance exercise program. Training will be performed three sessions per week. Aerobic exercise will be prescribed at 80–85% of heart rate reserve, and resistance exercise will be performed at 70–80% of one-repetition maximum. Each session will include warm-up, aerobic training, resistance training, and cool-down. Intervention 4: Control group: The control group will receive usual care and will not participate in any structured exercise program during the study period. Participants will be instructed to maintain their usual daily physical activity level. Yes - There is a plan to make this available What will be shared: De-identified individual participant data, study protocol, statistical analysis plan, analysis codes, and data dictionary will be made available to qualified researchers after publication of the primary study results. Requests will be reviewed by the research team based on scientific and ethical considerations. When: Access to data and documents will begin 6 months after publication of the primary study results and will remain available for 5 years. To whom: Academic researchers, scientists from research institutions, and qualified investigators submitting a valid scientific request will be eligible for access. Conditions: Data will be available for scientific research purposes, valid analyses, and advancing knowledge in multiple sclerosis and exercise science. Data reuse must comply with research ethics principles and must not attempt participant re-identification. Where to obtain: Requests for data access should be submitted to the corresponding investigator through the official email address of the research center. Final contact information will be provided after publication of the primary study results. How to obtain: Requests will be reviewed by the research team. After scientific and ethical approval, a data use agreement will be completed and access to de-identified data will be provided. Comments:
public Akram Jafari
Rahmatieh, Islamic Azad University Shahrekord Branch
Shahrekord Iran (Islamic Republic of) 8817630003 +98 38 3336 3001 Jafari.akm@gmail.com Islamic Azad University scientific Akram Jafari
Rahmatieh, Islamic Azad University Shahrekord Branch
Shahrekord Iran (Islamic Republic of) 8817630003 +98 38 1336 1001 Jafari.akm@gmail.com Islamic Azad University Iran (Islamic Republic of) Patients with relapsing-remitting multiple sclerosis according to the 2017 McDonald criteria Age between 25 and 45 years Expanded Disability Status Scale score between 1 and 4.5 No relapse during the previous three months No corticosteroid treatment during the previous three months Stable disease-modifying therapy for at least six months Ability to perform exercise testing and participate in the training program No participation in structured regular exercise training during the previous three months 25 years 45 years Both Progressive multiple sclerosis phenotype Cardiovascular disease or medical contraindications to exercise G35 G35 Multiple sclerosis Multiple sclerosis Behavior Behavior Behavior Behavior Intervention Low-dose Combined Aerobic-Resistance Exercise group: Participants will complete a 16-week combined aerobic-resistance exercise program. Training will be performed three sessions per week. Aerobic exercise will be prescribed at 50–60% of heart rate reserve, and resistance exercise will be performed at 50–60% of one-repetition maximum. Each session will include warm-up, aerobic training, resistance training, and cool-down. Intervention moderate-dose Combined Aerobic-Resistance Exercise group: Participants will complete a 16-week combined aerobic-resistance exercise program. Training will be performed three sessions per week. Aerobic exercise will be prescribed at 65–75% of heart rate reserve, and resistance exercise will be performed at 60–70% of one-repetition maximum. Each session will include warm-up, aerobic training, resistance training, and cool-down. Intervention high-dose Combined Aerobic-Resistance Exercise group: Participants will complete a 16-week combined aerobic-resistance exercise program. Training will be performed three sessions per week. Aerobic exercise will be prescribed at 80–85% of heart rate reserve, and resistance exercise will be performed at 70–80% of one-repetition maximum. Each session will include warm-up, aerobic training, resistance training, and cool-down. Control group: The control group will receive usual care and will not participate in any structured exercise program during the study period. Participants will be instructed to maintain their usual daily physical activity level. Change in serum neurofilament light chain concentration. Timepoint: Measurement at baseline before intervention and after completion of the 16-week exercise intervention. Method of measurement: Blood sampling and measurement of serum neurofilament light chain concentration using the Single Molecule Array method. Change in maximal cardiorespiratory fitness. Timepoint: Measurement at baseline before the intervention and after completion of the 16-week exercise intervention. Method of measurement: Using an incremental cardiopulmonary exercise test on a treadmill with respiratory gas analysis. Change in disease-related fatigue severity. Timepoint: Measurement at baseline before the intervention and after completion of the 16-week exercise intervention. Method of measurement: Using the Modified Fatigue Impact Scale. Change in walking performance. Timepoint: Measurement at baseline before the intervention and after completion of the 16-week exercise intervention. Method of measurement: Using the Six-Minute Walk Test. Change in cognitive function. Timepoint: Measurement at baseline before the intervention and after completion of the 16-week exercise intervention. Method of measurement: Using the Symbol Digit Modalities Test. Change in health-related quality of life. Timepoint: Measurement at baseline before the intervention and after completion of the 16-week exercise intervention. Method of measurement: Using the Multiple Sclerosis Quality of Life questionnaire containing 54 items. Change in serum brain-derived neurotrophic factor level. Timepoint: Measurement at baseline before the intervention and after completion of the 16-week exercise intervention. Method of measurement: Using enzyme-linked immunosorbent assay. Change in serum glial fibrillary acidic protein level. Timepoint: Measurement at baseline before the intervention and after completion of the 16-week exercise intervention. Method of measurement: Using the Single Molecule Array method. Change in serum interleukin-6 level. Timepoint: Measurement at baseline before the intervention and after completion of the 16-week exercise intervention. Method of measurement: Measurement of serum interleukin-6 level using enzyme-linked immunosorbent assay. Change in serum tumor necrosis factor-alpha level. Timepoint: Measurement at baseline before the intervention and after completion of the 16-week exercise intervention. Method of measurement: using enzyme-linked immunosorbent assay. Islamic Azad University Approved 2026-06-10 Islamic Azad University Shahrekord Branch Rahmatieh, Islamic Azad University Shahrekord Shahrekord Chahar-Mahal-va-Bakhtiari Iran (Islamic Republic of)