Melatonin in Patients With Multiple Sclerosis (MS).

Early Phase 1

Completed

Conditions: Relapsing Remitting Multiple Sclerosis

Interventions: Drug: 3 mg Melatonin
Drug: 5 mg Melatonin

Registration Number: NCT03498131

Lead Sponsor: Providence Health & Services

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3 mg Melatonin	3 mg Melatonin	Subjects will receive 3 mg melatonin once a day.
5 mg Melatonin	5 mg Melatonin	Subjects will receive 5 mg melatonin once a day.

Primary Outcome Measures

Name	Time	Method
Urine Melatonin Levels	Baseline (month 0), Month 3, Month 6, and Month 12	Changes in urinary 6-SMT in 24 hours, urine measured in nanograms per gram of creatinine

Secondary Outcome Measures

Name	Time	Method
Serum Melatonin Level	Baseline (month 0), Month 3, Month 6, and Month 12	Changes in morning blood levels of melatonin
Relapse Rate	12 months	Number of MS relapses during study
Modified Fatigue Impact Scale (MFIS)	Baseline (month 0), Month 3, Month 6, and Month 12	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, with three subscales: Physical range 0-36, Cognitive range 0-40, and Psychosocial range 0-8. Higher scores indicate higher level of fatigue.
Multiple Sclerosis Impact Scale-29 (MSIS-29)	Baseline (month 0), Month 3, Month 6, and Month 12	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). Individual item scores are summed to create a raw score, which is then transformed on a scale from 0 to 100 for each subscale. Higher scores indicate greater impact of MS on QoL.
Pittsburgh Sleep Quality Index (PSQI)	Baseline (month 0), Month 3, Month 6, and Month 12	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.
Patient Determined Disease Steps - Performance Scale (PDDS-PS)	Baseline (month 0), Month 3, Month 6, and Month 12	Changes in PDDS-PS: Patient Determined Disease Steps and Performance Scales (PDDS-PS) is a PRO for MS disease status. Performance Scales (PS) has 8 subscales: mobility range, hand function range, vision range, fatigue range, cognition range, bowel/bladder range, sensory range, and spasticity range. Subject self-classify their level of disability on a 0 to 8 scale (0=Normal to 8=Bedridden) with 8 being the most disabled for PDDS. For Performance Scales (PS) subject self-classify their level of disability on a 0 to 6 scale (0=Normal to 6=Bedridden) with 6 being the most disabled for PS - Mobility. Subject self-classify their level of disability on 0 to 5 scale (0=Normal to 5=Total Disability) with 5 being the most disabled for PS - hand function range, vision range, fatigue range, cognition range, bowel/bladder range, sensory range, and spasticity range.