Effects of DHA in Patients With Multiple Sclerosis

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).

• Modified Fatigue Impact Scale [Time frame: Throughout study completion, an average of 12 weeks]
• MSQoL-54 - Walking Status [Time frame: Throughout study completion, an average of 12 weeks]
• MSQoL-54 - Days Unable to Work or Attend School Due to Health [Time frame: Throughout study completion, an average of 12 weeks]
• MSQoL-54 - Hospital Admission in the Previous Year [Time frame: Throughout study completion, an average of 12 weeks]
• MSQoL-54 - Depressive Symptoms [Time frame: Throughout study completion, an average of 12 weeks]
• THERMOGRAPHY [Time frame: Pre, six weeks after the start and after the intervention (12 weeks)]
• SIT TO STAND TEST [Time frame: Throughout study completion, an average of 12 weeks]
• TIME UP AND GO test [Time frame: Throughout study completion, an average of 12 weeks]
• HAND GRIP [Time frame: Throughout study completion, an average of 12 weeks]
• IL-6 [Time frame: Pre, six weeks after the start and after the intervention (12 weeks)]
• MSQoL-54 - Multiple Sclerosis Disease Duration [Time frame: Baseline]