Effects of Therapeutic Exercise and Long-term Docosahexaenoic Acid (DHA) Supplementation on Physical, Physiological, Motor, Mental, and Cognitive Variables in Patients With Multiple Sclerosis.
Overview
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Sponsor
- Francisco Javier Martínez Noguera
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- ISOKINETIC
Overview
Brief Summary
This clinical trial will investigate the effects of combining therapeutic exercise with DHA supplementation in 100 patients with multiple sclerosis using a randomized controlled design. Participants, diagnosed according to the McDonald criteria, will undergo functional, cognitive, fatigue, and quality-of-life assessments through tools such as the EDSS, BRB-N, MFIS, EVA-f, and MSQoL-54. Physiological evaluations will include infrared thermography, isokinetic strength testing, perceived exertion (Modified Borg Scale), balance (Timed Up and Go), lower-limb power (Sit-to-Stand app), and handgrip strength. The study hypothesizes that this combined intervention will improve motor function, cognition, fatigue management, and overall quality of life by enhancing neuromuscular activation and metabolic efficiency.
Detailed Description
Design
Randomized clinical trial.
Study Period
Two years: from January 2024 to January 2026.
Population Selection Reference Population
The study sample will be recruited from the Multiple Sclerosis Association (AMDEM) in the Region of Murcia and the Neurology Department of Hospital Ribera Salud in Molina de Segura.
Eligible participants will be patients diagnosed with multiple sclerosis (MS) according to the McDonald criteria, aged approximately 18 to 65 years, who have not experienced relapse episodes in the month prior to inclusion, and have an Expanded Disability Status Scale (EDSS) score between 0.0 and 6.0, as well as the ability to voluntarily activate the tibialis anterior muscle.
Sample Size
Given the characteristics of the study, the target sample size is at least 100 participants, divided into four groups (n ≈ 25 per group) according to treatment.
Participants will be randomly assigned to one of four groups, each following a different therapeutic protocol:
Group 1: therapeutic exercise protocol three times per week throughout the study + daily DHA supplementation (4 capsule/day).
Group 2: same exercise protocol + placebo capsule (sunflower oil) identical in appearance, color, and dosage.
Group 3: DHA supplementation only (4 capsule/day).
Group 4: placebo capsule only (sunflower oil), identical to intervention groups.
Statistical Design
A one-way or repeated-measures ANOVA will be used to test for statistically significant differences among three or more dependent samples.
Measurement time points will be defined as follows:
T0: baseline (pre-intervention).
T1: midpoint of the intervention (approximately 1.5 months after initiation).
T2: immediately after completing the 3-month intervention protocol.
T3: 3 months after the end of the intervention.
Data Collection Participant Characteristics
Sensitive data will be collected regarding:
Age, sex, height, weight, medication use, relapse episodes in the months prior to the study, disability status, disease condition, and cognitive function.
Additional psychophysical information will be gathered using validated questionnaires administered before and after the intervention:
Disability will be assessed using the Expanded Disability Status Scale (EDSS).
A score of 0.0 represents normal physical function without disability.
3-4 indicates mild impairment not limiting daily or work activities.
5-6 indicates moderate disability, typically able to walk but requiring assistance for about 100 meters at level 6.
7-9 represents severe impairment, often confined to a wheelchair or bed.
Cognitive function will be assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), a validated tool for MS. It includes tests of selective recall, the 7/24 spatial recall test, the controlled oral word association test, and the paced auditory serial addition test (PASAT).
Fatigue will be measured using the Modified Fatigue Impact Scale (MFIS), assessing the perceived impact of fatigue on cognitive (10 items), physical (10 items), and psychosocial (20 items) functioning. Responses range from 0 (no problem) to 4 (extreme problem), with a maximum score of 160.
Quality of life will be measured with the Multiple Sclerosis Quality of Life-54 (MSQoL-54), a validated MS-specific scale that evaluates symptom severity, walking ability, absenteeism due to health, hospitalization history, depressive symptoms, and disease duration.
Functional Assessments
Pre, during and post--intervention.
Infrared thermography will capture whole-body thermal images before, during, and after the intervention as a non-invasive, reliable, and cost-effective diagnostic tool. Measurements will be taken:
Pre and post--intervention.
The Modified Borg Scale will be used to adjust exercise load intensity, maintaining perceived exertion between 5-7. If the score falls below 5, resistance will be increased by adding up to 5 kg. This will be recorded in the final session of each week.
The EVA-f scale (adapted fatigue visual analogue scale) will be used to measure subjective fatigue perception (0 = no fatigue; 10 = extreme fatigue) at the end of each training session.
The Sit-to-Stand App Test will be used to assess lower-limb power through video-based analysis of standing-up movements, providing values for time, power, and velocity (pre- and post-protocol).
The Timed Up and Go (TUG) Test will assess balance and fall risk. Participants will stand up from a chair, walk 3 meters, turn around, return, and sit down again. Two repetitions per session will be performed with one-minute rest intervals.
Handgrip strength will be measured (pre- and post-intervention) to assess upper-limb muscle strength.
Isokinetic strength tests will evaluate lower-limb strength (pre- and post-intervention).
Laboratory Tests
Serum analyses will include measurement of interleukin-6,
Blood samples will be collected at four time points:
Pre, during and immediately post-intervention.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Masking Description
The company that formulated the Omega-3 and placebo carried out the randomization, so no one on the research team or among the sponsors knew which group each study subject belonged to. The results of the randomization were sent to our laboratory after the study was completed to determine which subjects were in each group.
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •The patient sample comes from the Multiple Sclerosis Association (AMDEM) of the Murcia region and the neurology department of the Ribera Salud Hospital in Molina de Segura. Patients diagnosed with multiple sclerosis according to the McDonald criteria, aged between 18 and 65 (approximately), who have not suffered any flare-ups in the previous month and who have a score of 0.00 to 6 on the Expanded Disability Status Scale (EDSS) and are able to activate the tibialis anterior muscle will be eligible for the study.
Exclusion Criteria
- •Not fulfilling the inclusion criteria.
- •Having any problems performing the tests.
- •Having any problems taking the supplement or placebo.
Arms & Interventions
DHA
This group will take 2 g of DHA (4 capsules per day) for 3 months
Intervention: Docosahexaenoic Acid (DHA) Dietary Supplement (Dietary Supplement)
DHA + therapeutic exercise
This group will take 2 g of DHA (4 capsules per day) + therapeutic exercise for 3 months
Intervention: Docosahexaenoic Acid (DHA) Dietary Supplement (Dietary Supplement)
Sunflower oil
This group will take a placebo (4 capsules per day) for 3 months.
Intervention: Sunflower Oil (Dietary Supplement)
Sunflower oil + therapeutic exercise
This group will take a placebo (4 capsules per day) + therapeutic exercise for 3 months.
Intervention: Sunflower Oil (Dietary Supplement)
Outcomes
Primary Outcomes
ISOKINETIC
Time Frame: Throughout study completion, an average of 12 weeks
Measurement of isokinetic strength in the right leg N/m
Secondary Outcomes
- Modified Fatigue Impact Scale(Throughout study completion, an average of 12 weeks)
- MSQoL-54 - Walking Status(Throughout study completion, an average of 12 weeks)
- MSQoL-54 - Days Unable to Work or Attend School Due to Health(Throughout study completion, an average of 12 weeks)
- MSQoL-54 - Hospital Admission in the Previous Year(Throughout study completion, an average of 12 weeks)
- MSQoL-54 - Depressive Symptoms(Throughout study completion, an average of 12 weeks)
- THERMOGRAPHY(Pre, six weeks after the start and after the intervention (12 weeks))
- SIT TO STAND TEST(Throughout study completion, an average of 12 weeks)
- TIME UP AND GO test(Throughout study completion, an average of 12 weeks)
- HAND GRIP(Throughout study completion, an average of 12 weeks)
- IL-6(Pre, six weeks after the start and after the intervention (12 weeks))
- MSQoL-54 - Multiple Sclerosis Disease Duration(Baseline)
Investigators
Francisco Javier Martínez Noguera
Associate Researcher (Doctor of Sports Nutrition)
Universidad Católica San Antonio de Murcia