Relapsing Remitting Multiple SclerosisEarly Phase 1NCT03498131
Melatonin in Patients With Multiple Sclerosis (MS).
A Early Phase 1 study testing 3 mg Melatonin and 5 mg Melatonin in people with Relapsing Remitting Multiple Sclerosis, run by Providence Health & Services at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis
- What is being tested?
- 3 mg Melatonin and 5 mg Melatonin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 9 May 2018to 11 Dec 2023
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Being tested
- 3 mg Melatonin, 5 mg Melatonin
- Keywords
- Multiple Sclerosis, MS, Melatonin, Supplement
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3 mg MelatoninDrug
3 mg melatonin once each day
5 mg MelatoninDrug
5 mg Melatonin once each day
| Study group | Role | What they receive |
|---|---|---|
| 3 mg Melatonin | Experimental | Subjects will receive 3 mg melatonin once a day. Receives: Drug: 3 mg Melatonin |
| 5 mg Melatonin | Experimental | Subjects will receive 5 mg melatonin once a day. Receives: Drug: 5 mg Melatonin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urine Melatonin Levels
Changes in urinary 6-SMT in 24 hours, urine measured in nanograms per gram of creatinine
Measured: Baseline (month 0), Month 3, Month 6, and Month 12
Secondary outcomes (6)
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.
Measured: Baseline (month 0), Month 3, Month 6, and Month 12
Serum Melatonin Level
Changes in morning blood levels of melatonin
Measured: 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.
Measured: 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.
Measured: Baseline (month 0), Month 3, Month 6, and Month 12
Relapse Rate
Number of MS relapses during study
Measured: 12 months
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.
Measured: Baseline (month 0), Month 3, Month 6, and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study start9 May 2018
- Primary completion29 Jul 2022
- Study completion11 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Relapsing Remitting Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Providence Health & Services
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kyle Smoot, MD, Principal investigator, Providence Health & Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03498131
- Sponsor's protocol ID
- 2017000005
- Status last verified
- Mar 2025
- First submitted
- 6 Apr 2018
- Last updated
- 30 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39126937Ghareghani 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.
PubMed 35355991
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Potential Role of Melatonin in Subjects With Relapsing Multiple Sclerosis (MS)
- ClinicalTrials.gov ID
- NCT03498131
- Acronym / sponsor ID
- 2017000005
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Keywords
- Multiple Sclerosis, MS, Melatonin, Supplement
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Providence Health & ServicesUniversity, hospital or other
- Study start
- 9 May 2018 (actual)
- Primary completion
- 29 Jul 2022 (actual)
- Study completion
- 11 Dec 2023 (actual)
- First posted
- 13 Apr 2018 (actual)
- Results
- Posted 27 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| 3 mg Melatonin | Experimental | Drug: 3 mg MelatoninSubjects will receive 3 mg melatonin once a day. |
| 5 mg Melatonin | Experimental | Drug: 5 mg MelatoninSubjects will receive 5 mg melatonin once a day. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3 mg Melatonin3 mg melatonin once each day | Drug | 3 mg Melatonin |
| 5 mg Melatonin5 mg Melatonin once each day | Drug | 5 mg Melatonin |
Primary outcome
Urine Melatonin Levels
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Changes in urinary 6-SMT in 24 hours, urine measured in nanograms per gram of creatinine
6 secondary outcomes
Modified Fatigue Impact Scale (MFIS)
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Serum Melatonin Level
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Multiple Sclerosis Impact Scale-29 (MSIS-29)
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Pittsburgh Sleep Quality Index (PSQI)
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Relapse Rate
Time frame: 12 months
Patient Determined Disease Steps - Performance Scale (PDDS-PS)
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39126937Smoot 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.
- Derived from this study: PubMed 35355991Ghareghani 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.
- Providence Brain and Spine InstituteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kyle Smoot, MD principal investigator
Providence Health & Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing 3 mg Melatonin and 5 mg Melatonin in people with Relapsing Remitting Multiple Sclerosis, run by Providence Health & Services at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urine Melatonin Levels (time frame: Baseline (month 0), Month 3, Month 6, and Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03498131, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.