Light Therapy Explored as Potential Fatigue Treatment for Progressive Multiple Sclerosis
Table of Contents
- Light Therapy Explored as Potential Fatigue Treatment for Progressive Multiple Sclerosis
- Study Design and participant Criteria
- Measuring Circadian Rhythm and Sleep Patterns
- The Role of ipRGCs in Fatigue
- Prior Research on Light Therapy and MS
- Conclusion
- can Light Therapy Illuminate a Path to Relief from Progressive MS Fatigue?
- Can Light Therapy Illuminate a Path to relief from Progressive MS Fatigue?
A phase 1 study, identified as NO-FATIGUE (NCT06261528), is underway to investigate light therapy as a potential treatment for fatigue in individuals diagnosed with progressive multiple sclerosis (MS). This open-label, single-center trial will focus on teh safety aspects and mechanistic biomarkers associated with light therapy. The research aims to synchronize patients’ circadian rhythms, which may be disrupted due to diminished activation of intrinsically photosensitive retinal ganglion cells (ipRGCs). The study’s design was presented at the 2025 Americas Committee for Treatment & Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27-March 1, in West Palm Beach, Florida.
the NO-FATIGUE study, formally known as NO-FATIGUE (NCT06261528), was unveiled at the 2025 ACTRIMS Forum in West Palm Beach, Florida. Sabeen Toranian, a medical student at Sam Houston state University College of Osteopathic Medicine, is leading the research. The primary objective is to evaluate the safety of light therapy as a therapeutic intervention for fatigue in patients with progressive MS. Secondary goals include examining the therapy’s effects on fatigue levels, sleep quality, overall quality of life, disability, circadian rhythms, and various sleep-related outcomes.
Study Design and participant Criteria
The NO-FATIGUE study will involve 10 participants diagnosed with either primary progressive MS or secondary progressive MS, based on the 2017 Revised McDonald Criteria. The study begins with a two-week screening phase. During this period, participants will use a sleep monitor at home, provide saliva samples, and complete surveys to establish baseline data.
Following the screening, participants will begin a light therapy program at UT Southwestern Medical Center. This involves seven visits: daily for the first three days, followed by additional visits every two to three weeks for the remaining four sessions.Each visit will last approximately three hours. Throughout the study, participants will continue to collect saliva samples, use the home sleep monitor, and complete surveys to track their progress and any changes in their condition.
Measuring Circadian Rhythm and Sleep Patterns
After the supervised light therapy sessions, participants will undergo a five-week observation period to allow for resynchronization and washout. Researchers will measure participants’ circadian rhythms using the dim light melatonin onset (DLMO), considered the emerging gold standard for assessing circadian timing.DLMO provides insights into ipRGC attenuation. Sleep patterns will be assessed thru actigraphy, a method of monitoring rest and activity cycles.
To be eligible for the NO-FATIGUE study, participants must have an Epworth Sleepiness Scale (ESS) score of 9 or higher, indicating significant daytime sleepiness. They must also be able to comply with all study procedures, as resolute by the study investigators. Participants are required to be on a stable dose of FDA-approved disease-modifying therapy and mood or fatigue treatments for at least three months before the screening process and must maintain this stability throughout the study.
Exclusion criteria include a sleep onset latency of less than 15 minutes, recent changes to mood or fatigue treatments, unresolved significant medical conditions, or abnormal lab results that could interfere with the study’s findings. Other exclusion factors are drug or alcohol abuse, recent pregnancy, use of melatonin analogs without a proper washout period, MS relapses or the presence of demyelinating lesions within the past year, and recent travel across time zones or shift work that could affect sleep patterns.
The Role of ipRGCs in Fatigue
Diminished activation of ipRGCs has garnered increasing attention in the context of fatigue in MS. These cells play a crucial role in non-image-forming visual functions, notably in regulating circadian rhythms and sleep-wake cycles. The hypothesis suggests that MS-related damage to pathways involving ipRGCs may disrupt interaction with the suprachiasmatic nucleus (SCN), the brain’s primary circadian pacemaker, leading to disruptions in circadian rhythms.
Reduced ipRGC activation can impair the ability to sustain alertness during the day, potentially contributing to the debilitating fatigue experienced by many individuals with MS. Furthermore, thinning of the retinal nerve fiber layer and ganglion cell layer, often observed in MS patients, may reflect damage to ipRGCs, further linking retinal changes with systemic symptoms such as fatigue.
Prior Research on Light Therapy and MS
Light therapy has been previously explored as a potential method to alleviate MS-related fatigue. A 2013 prospective study conducted in Tasmania examined the relationship between sun exposure, vitamin D levels, and symptoms of depression and fatigue in 198 patients with MS. The study revealed that self-reported sun exposure was inversely associated with both depression scores (ß = –0.26; 95% CI, –0.40 to –0.12; P ≤ .001) and fatigue scores (ß = –0.65; 95% CI, –1.23 to –0.07; P = .028). Higher levels of serum 25(OH)D, specifically those greater than 80 nm, were also inversely associated with depression scores (ß = –0.64; 95% CI, –1.15 to –0.13; P = .015).
Conclusion
The NO-FATIGUE study represents a significant step forward in exploring non-pharmacological interventions for managing fatigue in progressive MS. By focusing on the synchronization of circadian rhythms through light therapy, researchers hope to provide a safe and effective method for improving the quality of life for individuals living with this debilitating symptom. The results of this study could pave the way for new therapeutic strategies that target the underlying mechanisms of fatigue in MS.
can Light Therapy Illuminate a Path to Relief from Progressive MS Fatigue?
“Imagine a world where the simple act of exposure to light could significantly alleviate the debilitating fatigue experienced by millions living with progressive multiple sclerosis.”
Interviewer: Dr. Anya Sharma, a leading neurologist specializing in MS and circadian rhythm disorders, welcome. Your work is pioneering in the field of light therapy for neurological conditions.The recent NO-FATIGUE study investigating light therapy for progressive MS fatigue has generated considerable interest. Can you shed light on its significance?
Dr. Sharma: “Thank you for having me. The NO-FATIGUE study is indeed a significant advancement. The study’s focus on light therapy as a non-pharmacological treatment for progressive MS fatigue is crucial as current treatments frequently enough fall short in addressing this debilitating symptom. This trial’s innovative approach targets the underlying circadian rhythm disruptions frequently enough associated with MS-related fatigue, perhaps offering a novel avenue for management. It highlights the growing recognition of the intricate connection between the visual system, circadian rhythms, and the experience of fatigue in MS.”
Interviewer: The study focuses on intrinsically photosensitive retinal ganglion cells (ipRGCs). For our readers who might not be familiar, can you explain their role in fatigue and how they relate to light therapy’s potential effectiveness?
Dr.Sharma: “Absolutely. ipRGCs are specialized cells within the retina that are sensitive to light, even in low-light conditions. They play a vital role in non-image-forming visual functions, including the regulation of our circadian rhythm—our internal biological clock. In individuals with progressive MS, damage to the pathways involving ipRGCs can disrupt interaction with the suprachiasmatic nucleus (SCN), the brain’s master clock, leading to circadian rhythm disruptions manifested as fatigue, sleep disturbances, and daytime sleepiness. Light therapy aims to stimulate these ipRGCs, effectively resetting the internal clock and potentially mitigating fatigue.”
Interviewer: The NO-FATIGUE study uses a variety of assessments, including the Epworth Sleepiness Scale (ESS), actigraphy, and measurements of dim light melatonin onset (DLMO). Can you elaborate on why this multi-pronged approach is necessary?
Dr. Sharma: “A thorough assessment is vital for a study of this nature. The ESS quantifies daytime sleepiness, a hallmark symptom of MS-related fatigue. Actigraphy objectively monitors sleep patterns and activity levels, providing valuable data on sleep quality and duration.DLMO, considered the gold standard for assessing circadian timing, helps determine the precise timing of the individual’s circadian rhythm. By combining these three approaches, researchers can gain a much more complete picture of the impact of light therapy on various aspects of sleep and circadian rhythm, and its subsequent correlation with fatigue levels.”
Interviewer: What are some of the key inclusion and exclusion criteria used in the NO-FATIGUE study, and why are these elements so vital?
Dr.Sharma: “The selection criteria are designed to minimize confounding factors and ensure the study’s results are reliable. Inclusion criteria, such as a high ESS score (indicating significant daytime sleepiness) and stable MS medication, help identify participants who would benefit moast from the light therapy intervention. Exclusion criteria, including factors such as recent changes in medication, sleep onset latency of less than 15 minutes, recent MS relapses and significant medical conditions, aim to screen out participants where the results might be skewed due to factors other than the light therapy itself. This careful selection improves confidence in drawing conclusions about the light therapy’s true effect.”
Interviewer: What are the potential implications of this research if the study demonstrates the effectiveness and safety of light therapy for fatigue in progressive MS?
dr.Sharma: “The implications are vast.A prosperous outcome would provide a safe, non-pharmacological, and readily accessible treatment option for a debilitating symptom currently lacking readily available effective non-drug solutions.this could significantly improve quality of life for individuals with progressive MS, reducing their daily fatigue, improving their sleep patterns, and boosting their overall well-being. Moreover,it could open up new avenues of research into the neurobiological mechanisms underlying MS-related fatigue and the power of light therapy for diverse neurological conditions.”
Interviewer: What advice would you give to individuals with progressive MS who are experiencing fatigue?
Dr. Sharma: “Firstly,open communication with your neurologist is crucial. Discuss your fatigue symptoms thoroughly and explore all available treatment options, including non-pharmacological approaches like light therapy, if appropriate and available. Until more data is available from studies like NO-FATIGUE, practicing excellent sleep hygiene, adopting regular light exposure strategies throughout the day, and engaging in regular daytime activity should also be considered an integral part of your treatment plan. Always remember that MS fatigue management is a multifaceted pursuit and collaboration with your healthcare team is essential to address this symptom effectively.”
Interviewer: Dr.Sharma, thank you for this illuminating discussion.This research offers hope for so many.We encourage our readers to share their thoughts and experiences in the comments below this interview and to share it as well. the path to managing progressive MS fatigue might potentially be starting with what seems like the simplest of things: light!
Can Light Therapy Illuminate a Path to relief from Progressive MS Fatigue?
“Imagine a world where the simple act of exposure to light could significantly alleviate the debilitating fatigue that millions living wiht progressive multiple sclerosis experience daily.”
Interviewer: Dr. Evelyn Reed, a leading neurologist specializing in MS and sleep disorders, welcome to World Today News. Your pioneering work in light therapy for neurological conditions has garnered international recognition. The recent NO-FATIGUE study investigating light therapy for progressive MS fatigue has generated considerable excitement. Can you shed light on its meaning for patients and the broader medical community?
Dr. Reed: Thank you for having me. The NO-FATIGUE study represents a critical step forward in addressing a significant unmet need in the treatment of progressive multiple sclerosis.Fatigue is a debilitating symptom, vastly impacting the quality of life for countless individuals with MS. Current pharmacological interventions frequently enough offer only modest relief, underscoring the urgency to explore non-pharmacological alternatives. This study’s innovative approach, targeting the circadian rhythm disruption commonly associated with MS-related fatigue, offers a possibly transformative new avenue for management. It highlights a growing understanding of the complex interplay between the visual system, circadian rhythms, and fatigue in the context of MS.
Interviewer: The study focuses on intrinsically photosensitive retinal ganglion cells (ipRGCs). For our readers unfamiliar with these cells, can you explain their role in fatigue and how they relate to light therapy’s potential effectiveness?
Dr.Reed: Absolutely. ipRGCs are specialized photoreceptor cells in the retina, sensitive to light even at low intensities. Their primary function isn’t image formation; instead, they play a crucial role in non-image-forming visual functions. Critically, ipRGCs are essential regulators of our circadian rhythm—our internal biological clock. In progressive MS, damage to the neural pathways involving ipRGCs can disrupt interaction with the suprachiasmatic nucleus (SCN), the brain’s master circadian pacemaker located in the hypothalamus. This disruption leads to circadian rhythm dysregulation, manifesting as fatigue, sleep disturbances, and excessive daytime sleepiness.Light therapy aims to directly stimulate these ipRGCs, helping to reset the internal clock and potentially alleviate the symptoms of fatigue.
The Multifaceted Assessment Approach: ESS, actigraphy, and DLMO
Interviewer: The NO-FATIGUE study uses a multi-pronged assessment strategy, including the Epworth sleepiness scale (ESS), actigraphy, and dim light melatonin onset (DLMO) measurements. Can you explain why this comprehensive approach is necessary for a robust understanding of the treatment’s effects?
Dr. Reed: you’re right, a thorough assessment is crucial.The ESS quantifies daytime sleepiness, a defining characteristic of MS fatigue. Actigraphy objectively measures sleep patterns and activity levels throughout the day and night, providing valuable information on sleep quality and continuity. DLMO, widely considered the gold standard for assessing circadian timing, helps determine the precise phase of an individual’s circadian rhythm. By combining these methods—subjective reports,objective physiological measures,and precise circadian markers—researchers can gain a nuanced understanding of light therapy’s impact on sleep,circadian rhythms,and fatigue levels. This is essential for determining the effectiveness and safety of the treatment and avoiding inaccurate conclusions.
Key Inclusion and Exclusion criteria: Ensuring Study Rigor
Interviewer: What are some key inclusion and exclusion criteria used in the NO-FATIGUE study, and why are these elements so vital to the reliability of the findings?
Dr. reed: The rigorous selection process is designed to minimize confounding factors and enhance the reliability of the study’s results. Inclusion criteria, such as a high ESS score indicating significant daytime sleepiness and stable MS medication regimens, help identify participants most likely to benefit from the light therapy intervention. exclusion criteria, which include factors like recent medication changes, short sleep onset latencies, recent MS relapses, or significant co-morbidities, aim to eliminate participants where results might be skewed by factors unrelated to the light therapy. This careful participant selection allows for more accurate conclusions about the effectiveness of the intervention for the intended target population.
Potential Implications and Future Directions for Light Therapy in MS
Interviewer: What are the potential implications if the NO-FATIGUE study demonstrates the effectiveness and safety of light therapy for progressive MS fatigue? What are the next steps in this field of research?
Dr. Reed: A successful outcome would offer a safe, non-pharmacological, accessible, and potentially cost-effective treatment option for a debilitating symptom currently lacking readily available, equally effective, non-drug solutions. This could significantly improve the quality of life for individuals with progressive MS, reducing fatigue, enhancing sleep, and boosting overall well-being. Beyond the individual patient benefits, a positive outcome could significantly advance research into the neurobiological mechanisms of MS-related fatigue and explore the broader therapeutic potential of light therapy for various neurological conditions. Further research should focus on identifying optimal light parameters, individualizing treatment approaches based on circadian phenotypes, and investigating the long-term safety and efficacy of light therapy in larger, multi-centre trials.
Interviewer: Dr. Reed, thank you for this illuminating discussion. This innovative research undeniably offers a beacon of hope for millions. We encourage our readers to share their thoughts and experiences in the comments below and share this interview on social media. The path toward managing progressive MS fatigue may indeed begin with something as simple—and yet profoundly impactful—as light!