Melatonin in Patients With Multiple Sclerosis (MS).

NCT03498131 | Completed Early Phase 1 Results DMC FDA Drug

• 1 other identifier: 2017000005
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

Multiple Sclerosis; MS; Melatonin; Supplement

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Modified Fatigue Impact Scale (MFIS)

  Baseline (month 0), Month 3, Month 6, and Month 12

• Serum Melatonin Level

  Baseline (month 0), Month 3, Month 6, and Month 12

• Multiple Sclerosis Impact Scale-29 (MSIS-29)

  Baseline (month 0), Month 3, Month 6, and Month 12

• Pittsburgh Sleep Quality Index (PSQI)

  Baseline (month 0), Month 3, Month 6, and Month 12

• Relapse Rate

  12 months

Study Arms (2)

3 mg Melatonin

EXPERIMENTAL

Subjects will receive 3 mg melatonin once a day.

Drug: 3 mg Melatonin

5 mg Melatonin

EXPERIMENTAL

Subjects will receive 5 mg melatonin once a day.

Drug: 5 mg Melatonin

Interventions

3 mg Melatonin DRUG

3 mg melatonin once each day

3 mg Melatonin

5 mg Melatonin DRUG

5 mg Melatonin once each day

5 mg Melatonin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Providence Health & Services: lead

Study Sites (1)

Providence MS Center

Portland, Oregon, 97225, United States

Location

Related Publications (2)

• Smoot K, Gervasi-Follmar T, Marginean H, Chen C, Cohan S. Impact of oral melatonin supplementation on urine and serum melatonin concentrations and quality-of-life measures in persons with relapsing multiple sclerosis. Mult Scler Relat Disord. 2024 Oct;90:105799. doi: 10.1016/j.msard.2024.105799. Epub 2024 Aug 3.

  PMID: 39126937 DERIVED

• 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.

  PMID: 35355991 DERIVED

Related Links

• Providence Brain and Spine Institute

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

1. Size of the patient population due to budget concerns. 2. No placebo arm, but the baseline values before the first dose of melatonin administration allowed each patient to severe as an internal control. 3. The time of year was not accounted for in analyzing the data. 4. The study was conducted during the SARS-CoV-2 pandemic leading to several missed data points. 5. A high number of patients that discontinued treatment.

Results Point of Contact

• Title: Director of PBSI /WC Clinical Research Program
• Organization: Providence Health & Services

Chiayi.Chen@providence.org

(503) 216-1012

Study Officials

• Kyle Smoot, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study is blinded to patients and providers.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 6, 2018
• First Posted: April 13, 2018
• Study Start: May 9, 2018
• Primary Completion: July 29, 2022
• Study Completion: December 11, 2023
• Last Updated: March 30, 2025
• Results First Posted: February 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)