Multiple Sclerosis
Conditions
Keywords
RCT; Hesperidin; Diet
Brief summary
This study is a randomised, double-blind, placebo-controlled trial investigating the effects of Hesperidin supplementation on cognitive function, fatigue, and stress. Participants will be randomly assigned to receive either 500mg of Hesperidin or a matching placebo daily for 12 weeks. The primary outcome is fatigue, with secondary outcomes including cognitive performance and mood. The trial seeks to determine if this dietary intervention offers symptom-alleviating benefits.
Detailed description
Multiple Sclerosis (MS) is a chronic autoimmune condition characterized by neuro-inflammation, oxidative stress, and demyelination, often resulting in debilitating fatigue and cognitive dysfunction. While disease-modifying therapies exist, there is a significant need for accessible, low-risk adjunct interventions to manage these daily symptoms. Hesperidin is a flavanone found primarily in citrus fruits (e.g., oranges, lemons). Preclinical research using Experimental Autoimmune Encephalomyelitis (EAE)-the standard animal model for MS-has demonstrated that hesperidin supplementation can reduce disease severity and incidence, likely due to its potent anti-inflammatory and antioxidant properties. However, there is a paucity of randomized controlled trials translating these findings to human MS populations. Study Design & Methodology. This study is a remote, randomised, double-blind, placebo-controlled, parallel-group trial in adults with Multiple Sclerosis. Participants will be randomized to receive either 500mg/day of Hesperidin or a matching placebo for a duration of 12 weeks. Statistical Analysis Plan. Data will be analysed using linear mixed-effects models. For the primary outcome (MFIS total score) and each secondary outcome, change from baseline to week 12 will be compared between intervention and placebo using fixed effects for group, time (baseline, week 12), and the group × time interaction, with a participant-level random intercept. The treatment effect will be estimated from the group × time interaction. Exploratory analyses will test whether baseline habitual diet modifies the intervention effect by adding a diet × group × time interaction term, with habitual diet operationalised using FFQ-derived polyphenol intake (energy-adjusted) and the Dietary Inflammatory Index (DII). In addition, exploratory symptom network analyses will examine whether the pattern of associations among symptoms differs between groups and changes from baseline to week 12.
Interventions
DIETARY_SUPPLEMENTHesperidin
500 mg/day Hesperidin capsules for 12 weeks
DIETARY_SUPPLEMENTPlacebo
Matching maltodextrin capsules for 12 weeks.
Sponsors
Swansea University
BioActor B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Multiple Sclerosis, Aged 18 years or older.
Exclusion criteria
* Known food allergies, intolerances, or significant gastrointestinal (GI) problems, Participants under the age of 18 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue | Baseline and Week 12 | Fatigue will be assessed using the Modified Fatigue Impact Scale (MFIS; Fisk et al., 1994), with the MFIS total score as the primary endpoint. MFIS subscale scores (physical, cognitive, psychosocial) and the Fatigue Severity Scale (FSS; Krupp et al., 1989) will be analysed as secondary outcomes to determine effects across different components of fatigue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mood and Stress | Baseline and Week 12 | Mood and stress symptoms will be assessed using the Depression Anxiety Stress Scales (DASS). Secondary outcomes will include the Depression, Anxiety, and Stress subscale scores. |
| Cognitive Function Battery | Baseline and Week 12 | Global cognitive performance will be summarised using a composite score calculated as the mean of standardized (z) scores from a prespecified cognitive battery including: Continuous Performance Task (attention), Auditory Verbal Learning Task (verbal memory), Digit Symbol Substitution Task (speed of information processing), Stroop Task (selective attention/inhibitory control), and Trail Making Task (processing speed/set-shifting). Scores will be coded so that higher values indicate better performance (completion time measures will be reverse-scored prior to standardisation).Individual task outcomes will also be analysed separately to explore domain-specific effects (attention, memory, speed). Fatigue/mood ratings are taken before and after the test to assess cognitive fatigue relating to the tests. |
Countries
United Kingdom
Contacts
CONTACTHayley Young, PhD
PRINCIPAL_INVESTIGATORHayley A Young, PHD
Swansea University
Outcome results
None listed