Melatonin in Patients With Multiple Sclerosis (MS).

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

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.

Study Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: 3 mg Melatonin; Drug: 5 mg Melatonin

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence MS Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3 mg Melatonin; Subjects will receive 3 mg melatonin once a day.	Drug: 3 mg Melatonin; 3 mg melatonin once each day
Experimental: 5 mg Melatonin; Subjects will receive 5 mg melatonin once a day.	Drug: 5 mg Melatonin; 5 mg Melatonin once each day

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse Rate	Number of MS relapses during study	12 months
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, with three subscales: Physical range 0-36, Cognitive range 0-40, and Psychosocial range 0-8. Higher scores indicate higher level of fatigue.	Baseline (month 0), Month 3, Month 6, and Month 12
Serum Melatonin Level	Changes in morning blood levels of melatonin	Baseline (month 0), Month 3, Month 6, and Month 12
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.	Baseline (month 0), Month 3, Month 6, and Month 12
Patient Determined Disease Steps - Performance Scale (PDDS-PS)	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.	Baseline (month 0), Month 3, Month 6, and Month 12
Multiple Sclerosis Impact Scale-29 (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). 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.	Baseline (month 0), Month 3, Month 6, and Month 12

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Investigators: Principal Investigator: Kyle Smoot, MD, Providence Health & Services

Publications and helpful links

General Publications

• Ghareghani M, Farhadi Z, Rivest S, Zibara K. PDK4 Inhibition Ameliorates Melatonin Therapy by Modulating Cerebral Metabolism and Remyelination in an EAE Demyelinating Mouse Model of Multiple Sclerosis. Front Immunol. 2022 Mar 9;13:862316. doi: 10.3389/fimmu.2022.862316. eCollection 2022.

Helpful Links

• Providence Brain and Spine Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2018
• Primary Completion (Actual): July 29, 2022
• Study Completion (Actual): December 11, 2023

Study Registration Dates

• First Submitted: April 6, 2018
• First Submitted That Met QC Criteria: April 6, 2018
• First Posted (Actual): April 13, 2018

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 23, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Melatonin; MS; Supplement
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antioxidants; Protective Agents; Melatonin
• Other Study ID Numbers: 2017000005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No