Melatonin in Patients With Multiple Sclerosis (MS).

• ClinicalTrials.gov Identifier: NCT03498131
• Recruitment Status: Active, not recruiting
• First Posted: April 13, 2018
• Last Update Posted: May 9, 2022
• Sponsor: Providence Health & Services
• Information provided by (Responsible Party): Providence Health & Services

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Relapsing Remitting Multiple Sclerosis	Drug: 3 mg Melatonin; Drug: 5 mg Melatonin	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The study is blinded to patients and providers.
• Primary Purpose: Treatment
• Official Title: Evaluating the Potential Role of Melatonin in Subjects With Relapsing Multiple Sclerosis (MS)
• Actual Study Start Date: May 9, 2018
• Estimated Primary Completion Date: September 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Changes in urine melatonin levels [ Time Frame: 3, 6, and 12 months ]
   Changes in 24-hour urinary 6-sulfatoxymelatonin and serum morning Melatonin over time

Secondary Outcome Measures :

1. Modified Fatigue Impact Scale (MFIS) [ Time Frame: 3, 6, and 12 months ]
   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.
2. Serum melatonin level [ Time Frame: 3, 6, and 12 months ]
   Changes is morning blood levels of melatonin
3. Multiple Sclerosis Impact Scale-29 (MSIS-29) [ Time Frame: 3, 6, and 12 months ]
   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.
4. Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 3, 6, and 12 months ]
   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.
5. Relapse Rate [ Time Frame: 12 months ]
   Number of MS relapses during study
6. Patient Determined Disease Steps - Performance Scale (PDDS-PS) [ Time Frame: 3, 6, and 12 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Oregon

Providence MS Center

Portland, Oregon, United States, 97225

Sponsors and Collaborators

Providence Health & Services

Investigators

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

More Information

Additional Information:

Providence Brain and Spine Institute 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Providence Health & Services
• ClinicalTrials.gov Identifier: NCT03498131
• Other Study ID Numbers: 2017000005
• First Posted: April 13, 2018
• Last Update Posted: May 9, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Providence Health & Services:

Multiple Sclerosis; MS; Melatonin; Supplement

Additional relevant MeSH terms:

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Melatonin; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Central Nervous System Depressants