A pioneering clinical trial is set to explore the potential of light therapy as a novel treatment approach for fatigue in progressive multiple sclerosis (MS) patients. The Phase 1 NO-FATIGUE trial (NCT06261528) will evaluate both safety parameters and mechanistic biomarkers, focusing on the synchronization of patients' circadian rhythms through targeted light exposure.
The single-center, open-label study will recruit 10 participants diagnosed with either primary or secondary progressive MS according to the 2017 Revised McDonald Criteria. The trial design incorporates a comprehensive assessment protocol spanning multiple weeks.
Study Design and Implementation
Participants will first undergo a 2-week screening period involving home-based sleep monitoring, saliva sample collection, and survey completion. The core intervention consists of seven visits to UT Southwestern Medical Center, with an intensive initial phase of daily sessions for three consecutive days, followed by three additional sessions spaced 2-3 weeks apart. Each therapeutic session will last approximately three hours.
The research team will track multiple parameters throughout the study period. Key measurements include:
- Dim light melatonin onset (DLMO) for circadian rhythm assessment
- Actigraphy for sleep pattern monitoring
- Quality of life metrics
- Disability progression
- Fatigue and sleepiness scales
Patient Selection Criteria
The trial has established specific eligibility requirements to ensure appropriate patient selection. Key inclusion criteria comprise:
- Epworth Sleepiness Scale (ESS) score ≥ 9
- Stable disease-modifying therapy for at least three months
- Consistent dosing of any mood or fatigue treatments
Exclusion factors encompass sleep onset latency under 15 minutes, recent MS relapses, active demyelinating lesions, and lifestyle factors that could confound results, such as shift work or recent trans-timezone travel.
Scientific Rationale
The study's foundation lies in emerging research on intrinsically photosensitive retinal ganglion cells (ipRGCs) and their role in MS-related fatigue. These specialized cells are crucial for non-visual functions, particularly circadian rhythm regulation and sleep-wake cycle maintenance. MS-related damage to ipRGC pathways may disrupt communication with the suprachiasmatic nucleus (SCN), potentially contributing to the severe fatigue experienced by MS patients.
Supporting this approach, previous research in Tasmania involving 198 MS patients demonstrated significant correlations between sun exposure and symptom severity. The study found that increased sun exposure was inversely associated with both depression (β = –0.26; 95% CI, –0.40 to –0.12; P ≤.001) and fatigue scores (β = –0.65; 95% CI, –1.23 to –0.07; P = .028).
Monitoring and Assessment
Following the supervised light therapy sessions, participants will enter a 5-week observation period designed for resynchronization and washout. This phase will help researchers evaluate the durability of any therapeutic effects and monitor for potential delayed responses or adverse events.
The trial represents a significant step forward in understanding non-pharmacological approaches to managing MS-related fatigue, potentially offering a new therapeutic option for patients with progressive forms of the disease. Results from this study could pave the way for larger-scale investigations into light therapy's role in MS symptom management.
