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

Tracking Information

• First Submitted Date: April 6, 2018
• First Posted Date: April 13, 2018
• Last Update Posted Date: May 9, 2022
• Actual Study Start Date: May 9, 2018
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 6, 2018)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 9, 2018)

• 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.
• Serum melatonin level [ Time Frame: 3, 6, and 12 months ]
  Changes is morning blood levels of melatonin
• 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.
• 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.
• Relapse Rate [ Time Frame: 12 months ]
  Number of MS relapses during study
• 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.

Original Secondary Outcome Measures (submitted: April 6, 2018)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Melatonin in Patients With Multiple Sclerosis (MS).
• Official Title: Evaluating the Potential Role of Melatonin in Subjects With Relapsing Multiple Sclerosis (MS)
• 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.

• Study Type: Interventional
• Study Phase: Early Phase 1

Study Design

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

• Condition: Relapsing Remitting Multiple Sclerosis

Intervention

• Drug: 3 mg Melatonin
  3 mg melatonin once each day
• Drug: 5 mg Melatonin
  5 mg Melatonin once each day

Study Arms

• Experimental: 3 mg Melatonin
  Subjects will receive 3 mg melatonin once a day.
  Intervention: Drug: 3 mg Melatonin
• Experimental: 5 mg Melatonin
  Subjects will receive 5 mg melatonin once a day.
  Intervention: Drug: 5 mg Melatonin

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 6, 2018): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03498131
• Other Study ID Numbers: 2017000005
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Providence Health & Services
• Original Responsible Party: Same as current
• Current Study Sponsor: Providence Health & Services
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Providence Health & Services
• Verification Date: May 2022