Healthy Eating and Active Living for People Living With Multiple Sclerosis (HEAL MS): A Lifestyle Program for People With Multiple Sclerosis

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by neurodegeneration, demyelination, and progressive disability. Although current treatments primarily focus on immune suppression, growing evidence indicates that non-immune mechanisms, including mitochondrial dysfunction, metabolic imbalance, and chronic systemic inflammation, play a significant role in disease progression and symptom burden. Multi-omics studies have identified disruptions in mitochondrial proteins, lipid and amino acid metabolism, and inflammatory signaling pathways in individuals with MS, suggesting that systemic metabolic processes contribute to disease activity and may represent modifiable therapeutic targets.

HEAL MS (Healthy Eating and Active Living for Multiple Sclerosis) was developed to address these upstream biological drivers through a structured lifestyle intervention integrating nutrition, physical activity, sleep optimization, and stress regulation. The program is culturally adapted for the UAE population and delivered through a hybrid model combining in-person onboarding and digital support via a bilingual (Arabic-English) mobile application that facilitates behavioral tracking, education, and participant engagement.

This study is a 24-month pilot interventional study designed to evaluate the feasibility, acceptability, and biological impact of the HEAL MS program in individuals with relapsing-remitting or progressive MS. Thirty participants will be recruited from collaborating MS clinics. The study uses a within-subject design consisting of a 12-week observation (control) period followed by a 12-week lifestyle intervention. Assessments are conducted at four timepoints: baseline, pre-intervention, post-intervention, and three months after completion of the intervention. This design allows each participant to serve as their own control, improving statistical sensitivity and reducing inter-individual variability.

The intervention targets four behavioral domains. Adaptive movement training consists of supervised small-group sessions conducted twice weekly using functional resistance exercises based on bodyweight, resistance bands, and suspension training. Exercises are designed to improve strength, neuromuscular coordination, and mitochondrial resilience while remaining scalable to accommodate MS-related fatigue and mobility limitations. The nutrition component emphasizes anti-inflammatory, nutrient-dense whole foods with a macronutrient distribution of approximately 40% carbohydrates, 30% protein, and 30% fat. Personalized calorie targets are calculated using the Mifflin-St Jeor equation, and participants receive meal delivery during the initial two weeks to facilitate adherence before transitioning to guided self-preparation. Sleep optimization focuses on circadian-aligned behavioral strategies such as consistent sleep schedules, screen-light reduction, and timing of meals and exercise. Stress regulation includes daily breath-based practices, mindfulness exercises, and vagal nerve-stimulating techniques designed to support autonomic balance. Participant engagement and adherence are supported through daily behavioral tracking using the mobile application.

The study integrates biological, clinical, and behavioral outcomes to evaluate the mechanistic impact of the intervention. Blood samples collected at each assessment will undergo routine clinical chemistry testing and high-resolution molecular profiling. Proteomic analysis will be performed using the Olink Reveal platform, enabling multiplex quantification of over 1,000 plasma proteins related to immune signaling, inflammation, oxidative stress, and metabolic regulation. Metabolomic profiling will be conducted using nuclear magnetic resonance spectroscopy to quantify approximately 250 circulating metabolic biomarkers related to mitochondrial function and systemic metabolism.

Additional outcome measures include body composition assessment using multi-frequency bioelectrical impedance analysis, validated functional performance tests (6-minute step test, five-times-sit-to-stand test, and grip strength), and psychometric instruments assessing fatigue, mood, sleep quality, cognitive performance, and quality of life. Wearable monitoring devices will be used to capture sleep duration, activity levels, and heart rate variability as indicators of physiological recovery and autonomic regulation.

By integrating behavioral intervention with high-resolution molecular profiling, HEAL MS aims to generate mechanistic insight into how lifestyle modification influences metabolic, inflammatory, and mitochondrial pathways in MS. Findings from this pilot study will inform the feasibility and design of larger randomized trials investigating lifestyle-based strategies as complementary approaches to disease management.

• Multi-Domain Lifestyle Intervention (Other): The intervention is a 12-week multi-domain lifestyle program. It targets four behavioral domains: physical activity, nutrition, sleep, and stress regulation. Participants attend twice-weekly supervised online exercise sessions using scalable functional movements performed with bodyweight, resistance bands, and suspension training. The nutrition component provides individualized meal plans based on maintenance calories, emphasizing anti-inflammatory, whole-food nutrition with a macronutrient distribution of approximately 40% carbohydrates, 30% protein, and 30% fat. During the first two weeks, meals are delivered to support adherence. Sleep optimization focuses on circadian-aligned behaviors such as consistent sleep timing and reduced evening light exposure. Stress regulation includes daily breathing exercises, mindfulness practices, and vagal nerve-stimulating techniques. Participants track dadaily behaviors, wellbeing, and wearable data using a billiungual mobile app.

Primary outcomes

• Recruitment Rate (Number of Participants Enrolled per Month) [From study start (Month 0) to completion of recruitment (approximately Month 12)]: Number of eligible participants enrolled into the study per month, calculated from the number of participants who consent and complete baseline assessment.
• Retention Rate (Percentage of Participants Completing All Study Assessments) [Baseline to 36 weeks (end of follow-up)]: Percentage of enrolled participants who complete all four assessment timepoints (baseline, pre-intervention, post-intervention, and 3-month follow-up).
• Exercise Adherence (Percentage of Completed Scheduled Exercise Sessions) [Weeks 13-24 (12-week intervention period)]: Proportion of prescribed exercise sessions attended (twice-weekly supervised sessions) during the 12-week intervention period.
• Mobile Application Engagement (Average Daily Completion Rate of App-Based Logs) [Weeks 13-24 (12-week intervention period)]: Average proportion of days participants complete daily logs (including energy, fatigue, mood, sleep, and adherence tracking) via the HEAL MS mobile application.
• Acceptability of HEAL MS Intervention (Participant Satisfaction Score) [Week 24 (post-intervention assessment)]: Participant-reported satisfaction with the intervention, assessed using a standardized post-intervention questionnaire (e.g., Likert scale rating of overall experience, usability, and perceived benefit).

Secondary outcomes

• Change in Plasma C-Reactive Protein (CRP) Concentration (mg/L) [Baseline (Week 0), Pre-Intervention (Week 12), Post-Intervention (Week 24), and Follow-up (Week 36)]: CRP will be measured using standard clinical blood chemistry assays. Mean change in CRP concentration will be calculated across timepoints to assess systemic inflammation.
• Change in Plasma Interleukin-6 (IL-6) Levels (pg/mL) [Baseline (Week 0), Week 12, Week 24, Week 36]: IL-6 will be quantified using proteomic analysis (Olink platform). Mean change across timepoints will be used to assess inflammatory signaling.
• Change in Plasma Proteomic Profile (Normalized Protein Expression Units) [Baseline (Week 0), Week 12, Week 24, Week 36]: Quantitative proteomic profiling will be performed using the Olink Reveal platform. A composite score derived from selected proteins related to immune function, oxidative stress, and metabolism will be analyzed using normalized protein expression (NPX) values.
• Change in Circulating Metabolomic Biomarkers (Concentration Units, mmol/L or µmol/L) [Baseline, Week 12, Week 24, Week 36]: Metabolomic profiling will be conducted using nuclear magnetic resonance (NMR) spectroscopy, quantifying biomarkers related to lipid metabolism, amino acids, and energy pathways. Mean changes in selected metabolites will be analyzed.
• Change in Perceived Stress Score (Perceived Stress Scale, PSS-10) [Baseline (Week 0), Week 12, Week 24, Week 36]: Perceived stress will be assessed using the 10-item Perceived Stress Scale (PSS-10), a validated measure of perceived stress over the past month (score range: 0-40; higher scores indicate greater perceived stress).
• Change in Daily Emotional Wellbeing Score (App-Based Self-Assessment) [Weeks 0, 12, 24, and 36 (7-day averages prior to each assessment)]: Emotional wellbeing will be assessed using a daily app-based self-report measure (mood and emotional state), collected using a visual Likert or pictorial (Self-Assessment Manikin-style) scale. Scores will be averaged over 7-day periods prior to each assessment timepoint (range: 0-4; higher scores indicate worse wellbeing).

Sex: All, ages: 18 Years to 50 Years

Inclusion Criteria:

* Confirmed MS diagnosis (McDonald criteria)
* EDSS score ≤ 6.5 (i.e., ambulatory with or without assistance)
* Stable disease-modifying therapy for ≥ 3 months
* Age 18-50
* Proficiency in English or Arabic
* Clearance to participate in a structured exercise program
* Ability to walk, sit and stand independently, and perform light-to-moderate movement patterns, even with modifications
* Ability and digital literacy to interact with the bilingual HEAL MS mobile app and
* Access to a computer for participation in online sessions

Exclusion Criteria:

* Significant cognitive impairment affecting app use and comprehension of the intervention
* MS relapse within the past 3 months
* Pregnancy or planned pregnancy
* Unmanaged psychiatric disorders
* Other immune-related or chronic inflammatory or metabolic diseases
* Concurrent enrollment in another lifestyle intervention

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• Youssef Idaghdour, Professor, Principal investigator, New York University Abu Dhabi