Clinical trial NCT03498131: Melatonin in Patients With Multiple Sclerosis (MS).
Official title: Evaluating the Potential Role of Melatonin in Subjects With Relapsing Multiple Sclerosis (MS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Relapsing Remitting Multiple Sclerosis
Keywords: Multiple Sclerosis
MS
Melatonin
Supplement
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
First posted: 2018-04-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Urine Melatonin Levels
timeFrame: Baseline (month 0), Month 3, Month 6, and Month 12
Secondary outcomes:
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: Baseline (month 0), Month 3, Month 6, and Month 12
measure: Serum Melatonin Level
timeFrame: Baseline (month 0), Month 3, Month 6, and Month 12
measure: Multiple Sclerosis Impact Scale-29 (MSIS-29)
timeFrame: Baseline (month 0), Month 3, Month 6, and Month 12
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Baseline (month 0), Month 3, Month 6, and Month 12
measure: Relapse Rate
timeFrame: 12 months
measure: Patient Determined Disease Steps - Performance Scale (PDDS-PS)
timeFrame: Baseline (month 0), Month 3, Month 6, and Month 12
Other outcomes:
Locations:
city: Portland
country: United States
facility: Providence MS Center
state: Oregon
Study officials:
affiliation: Providence Health & Services
name: Kyle Smoot, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.