Melatonin in Patients With Multiple Sclerosis (MS).

Study Overview
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Brief Summary
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To date, there are no published data on the role of melatonin supplementation or the appropriate dose for patients with multiple sclerosis. Because of the potential benefits of melatonin, this pilot study will be an exploratory investigation to evaluate the effect of supplementing melatonin in subjects with multiple sclerosis who are taking an oral disease modifying therapy (DMT) for 6 months or longer. It is our intent that the results of this study will support the rationale and be a prelude to a larger trial which can focus on clinical efficacy of melatonin therapy outcomes.

Detailed Description
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The primary objective of this study is to evaluate the change in 24 hour urinary 6-sulfatoxymelatonin (6SMT) collected for 24 hours in two twelve hour sessions. The secondary objectives are to evaluate the change in serum morning melatonin level. In addition, quality of life (QOL) measures will be assessed including the Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Impact Scale (MSIS-29), and the Pittsburgh Sleep Quality Index (PSQI). Clinical objectives include the number of relapses during the trial and a change in the Patient Determined Disease Steps (PDDS) & Performance Scales (PS). The pilot study is a one-year randomized, rater- and dose-blinded trial evaluating the potential role of melatonin in subjects with relapsing multiple sclerosis who have been taking a stable dose of an oral disease modifying therapy (DMT) for at least 6 months. The oral DMTs include dimethyl fumarate, fingolimod, teriflunomide, diroximel fumarate, siponimod, and ozanimod. Thirty subjects with relapsing forms of multiple sclerosis who meet all of the eligibility criteria will be enrolled at Providence Neurological Specialties in Portland, Oregon.

Official Title
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Evaluating the Potential Role of Melatonin in Subjects With Relapsing Multiple Sclerosis (MS)

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: 3 mg Melatonin
* Drug: 5 mg Melatonin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects with relapsing forms of MS who have been on a stable dose of dimethyl fumarate, fingolimod, teriflunomide, diroximel fumarate, siponimod, or ozanimod for 6 months or longer Confirmed diagnosis of Relapsing MS Women of childbearing potential must employ proven methods to prevent pregnancy during the course of the trial; the acceptable method will be left to the judgment of the investigator Not pregnant or lactating No evidence of significant cognitive or psychiatric disorder Able to understand the purpose and risks of the study Must be willing to sign an informed consent and follow the protocol requirements Exclusion Criteria: Use of melatonin within 30 days of enrollment The addition of any sleep aide or change in dose within 30 days of enrollment or during the trial The addition or change in dose of Vitamin D within 30 days of enrollment or during the trial Change in DMT during the trial Steroid therapy within 30 days of enrollment Use of anticoagulation at the time of enrollment and during the trial The addition of an antidepressant is not allowed during the study period; if on an antidepressant at screening, the dose must be stable 30 days prior to enrollment and dose changes are prohibited during the study The addition or change in dose of any stimulants, including but not limited to, amantadine, armodafinil, methylphenidate, or modafinil within 30 days of enrollment or during the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomly assigned to receive melatonin at 3 milligrams (mg) once a day or 5mg once a day. The study drug will be taken at 21:00 each day ± 2 hours.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3 mg Melatonin<br>Subjects will receive 3 mg melatonin once a day. | Drug: 3 mg Melatonin<br>* 3 mg melatonin once each day<br>|
| Experimental: 5 mg Melatonin<br>Subjects will receive 5 mg melatonin once a day. | Drug: 5 mg Melatonin<br>* 5 mg Melatonin once each day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in urine melatonin levels | Changes in 24-hour urinary 6-sulfatoxymelatonin and serum morning Melatonin over time | 3, 6, and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Fatigue Impact Scale (MFIS) | Changes in the MFIS: Modified Fatigue Impact Scale (MFIS) is a PRO, consisting of 21 statements that describe the effect of fatigue. Subject will choose an answer (0= never to 4=always) that best describes how fatigue has affected them in the past 4 weeks. Item scores are summed to a total score. The total MFIS score ranges from 0 to 84. Higher scores indicate higher level of fatigue. | 3, 6, and 12 months | 
| Serum melatonin level | Changes is morning blood levels of melatonin | 3, 6, and 12 months | 
| Multiple Sclerosis Impact Scale-29 (MSIS-29) | Changes in the MSIS-29: Multiple Sclerosis Impact Scale (MSIS) is a patient reported outcome (PRO) measure, consisting of two subscales- physical impact of MS (20 items) and psychological impact (9 items). It asks subject to rate the impact MS has their daily life in the past 2 weeks (1=low impact to 4=large impact). Scores from individual items are summed to a total score. Physical impact score ranges from 20-80 and psychological impact scores ranges from 9-36. Higher scores indicate greater impact of MS on QoL. | 3, 6, and 12 months | 
| Pittsburgh Sleep Quality Index (PSQI) | Changes in PSQI: Pittsburgh Sleep Quality Index (PSQI) asks 10 sets of questions about sleep quality and pattern in the past month. The scale derive 7 component scores based on a 0 to 3 scale (0= no difficulty, 3=severe difficulty) which are summed to a global score (range 0 to 21). Higher scores indicates worse sleep quality. | 3, 6, and 12 months | 
| Relapse Rate | Number of MS relapses during study | 12 months | 
| Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Changes in PDDS-PS: Patient Determined Disease Steps Performance Scales (PDDS-PS) is a PRO for MS disease status. Subject self-classify their level of disability on a 0 to 8 scale (0=Normal to 8=Bedridden) with 8 being the most disabled. | 3, 6, and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, MS, Melatonin, Supplement