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NCT03498131

Melatonin in Patients With Multiple Sclerosis (MS).

Completed EARLY_PHASE1 Results posted Last updated 30 March 2025
What this trial tests

EARLY_PHASE1 trial testing 3 mg Melatonin in Relapsing Remitting Multiple Sclerosis in 30 participants. Completed in 11 December 2023.

Timeline
9 May 2018
Primary endpoint
29 July 2022
11 December 2023

Quick facts

Lead sponsorProvidence Health & Services
PhaseEARLY_PHASE1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment30
Start date9 May 2018
Primary completion29 July 2022
Estimated completion11 December 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Providence Health & Services — full company profile →

Who can join

Adults 18 to 65, any sex, with Relapsing Remitting Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Urine Melatonin Levels Primary · 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

Baseline (month 0)
GroupValue95% CI
3 mg Melatonin1910 – 55
5 mg Melatonin2216 – 91
Month 3
GroupValue95% CI
3 mg Melatonin925214 – 1305
5 mg Melatonin1,687808 – 4,817
Month 6
GroupValue95% CI
3 mg Melatonin1,030424 – 2,245
5 mg Melatonin2,5091,780 – 4,784
Month 12
GroupValue95% CI
3 mg Melatonin1,02031 – 1,604
5 mg Melatonin4,339653 – 16,194
Modified Fatigue Impact Scale (MFIS) Secondary · Baseline (month 0), Month 3, Month 6, and Month 12

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.

MFIS Score [0-84] - Baseline
GroupValue95% CI
3 mg Melatonin2516.0 – 25.0
5 mg Melatonin248.0 – 24.0
MFIS Score [0-84] - 3 months visit
GroupValue95% CI
3 mg Melatonin16.59.50 – 16.5
5 mg Melatonin22.014.5 – 22.0
MFIS Score [0-84] - 6 months visit
GroupValue95% CI
3 mg Melatonin224.75 – 22.0
5 mg Melatonin21.511.2 – 21.5
MFIS Score [0-84] - 12 months visit
GroupValue95% CI
3 mg Melatonin20.56.00 – 20.5
5 mg Melatonin19.012.0 – 19.0
Serum Melatonin Level Secondary · Baseline (month 0), Month 3, Month 6, and Month 12

Changes in morning blood levels of melatonin

Baseline (Month 0)
GroupValue95% CI
3 mg Melatonin54 – 9
5 mg Melatonin54 – 13
Month 3
GroupValue95% CI
3 mg Melatonin148 – 44
5 mg Melatonin6932 – 111
Month 6
GroupValue95% CI
3 mg Melatonin3512 – 51
5 mg Melatonin7246 – 193
Month 12
GroupValue95% CI
3 mg Melatonin298 – 56
5 mg Melatonin9720 – 261
Multiple Sclerosis Impact Scale-29 (MSIS-29) Secondary · Baseline (month 0), Month 3, Month 6, and Month 12

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.

Physical - Baseline
GroupValue95% CI
3 mg Melatonin103.00 – 10.0
5 mg Melatonin9.005.00 – 9.00
Physical - 3 Months Visit
GroupValue95% CI
3 mg Melatonin4.54.00 – 4.50
5 mg Melatonin8.004.00 – 8.00
Physical - 6 months visit
GroupValue95% CI
3 mg Melatonin7.02.50 – 7.0
5 mg Melatonin5.002.00 – 5.00
Physical - 12 months visit
GroupValue95% CI
3 mg Melatonin9.002.00 – 9.00
5 mg Melatonin8.002.00 – 8.00
Psychological - Baseline
GroupValue95% CI
3 mg Melatonin8.04.50 – 8.00
5 mg Melatonin14.09.50 – 14.0
Psychological - 3 months visit
GroupValue95% CI
3 mg Melatonin12.56.50 – 12.5
5 mg Melatonin8.03.00 – 8.00
Psychological - 6 months visit
GroupValue95% CI
3 mg Melatonin3.03.00 – 3.00
5 mg Melatonin9.508.00 – 9.50
Psychological - 12 months visit
GroupValue95% CI
3 mg Melatonin8.00.750 – 8.00
5 mg Melatonin11.06.00 – 11.0
Pittsburgh Sleep Quality Index (PSQI) Secondary · Baseline (month 0), Month 3, Month 6, and Month 12

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.

PSQI Global - Base Line
GroupValue95% CI
3 mg Melatonin7.05.5 – 7.0
5 mg Melatonin6.04.5 – 6.0
PSQI Global - 3 month Visit
GroupValue95% CI
3 mg Melatonin5.53.0 – 5.5
5 mg Melatonin9.06.0 – 9.0
PSQI Global - 6 months visit
GroupValue95% CI
3 mg Melatonin6.04.0 – 6.0
5 mg Melatonin8.04.5 – 8.0
PSQI Global - 12 month Visit
GroupValue95% CI
3 mg Melatonin5.02.5 – 5.0
5 mg Melatonin7.05.0 – 7.0
Relapse Rate Secondary · 12 months

Number of MS relapses during study

o Relapse
GroupValue95% CI
3 mg Melatonin13
5 mg Melatonin15
1 Relapse
GroupValue95% CI
3 mg Melatonin2
5 mg Melatonin0
Patient Determined Disease Steps - Performance Scale (PDDS-PS) Secondary · Baseline (month 0), Month 3, Month 6, and Month 12

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 - Mobilit

Patient Determined Disease Steps - Baseline
GroupValue95% CI
3 mg Melatonin1.00 – 1.0
5 mg Melatonin00 – 0
Patient Determined Disease Steps - 3 Month Visit
GroupValue95% CI
3 mg Melatonin1.00 – 1.0
5 mg Melatonin00 – 0
Patient Determined Disease Steps - 6 Month Visit
GroupValue95% CI
3 mg Melatonin0.500 – 0.50
5 mg Melatonin0.500 – 0.50
Patient Determined Disease Steps - 12 Month Visit
GroupValue95% CI
3 mg Melatonin0.500 – 0.50
5 mg Melatonin1.00 – 1.0
Performance Scale - Mobility - Baseline
GroupValue95% CI
3 mg Melatonin00 – 0
5 mg Melatonin00 – 0
Performance Scale - Mobility - 3 Month
GroupValue95% CI
3 mg Melatonin00 – 0
5 mg Melatonin00 – 0
Performance Scale - Mobility - 6 Month
GroupValue95% CI
3 mg Melatonin0.5000 – 0.500
5 mg Melatonin00 – 0
Performance Scale - Mobility - 12 Month
GroupValue95% CI
3 mg Melatonin00 – 0
5 mg Melatonin00 – 0

Adverse events — posted to ClinicalTrials.gov

Time frame: The period during which all adverse events and serious adverse events collected began after the informed consent is obtained and ended 30 days following the last administration of study treatment and IP assignments unblinded or study discontinuation/termination, whichever is earlier, up to 5 years.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

3 mg Melatonin
Serious: 1/15 (7%)
Deaths: 0/15
5 mg Melatonin
Serious: 0/15 (0%)
Deaths: 0/15

Serious adverse events (3 terms)

ReactionSystem3 mg Melatonin5 mg Melatonin
Near-syncopeCardiac disorders——
Pacemaker insertionCardiac disorders——
Heart blockCardiac disorders——
Other adverse events (144 terms — click to expand)

ReactionSystem3 mg Melatonin5 mg Melatonin
Upper respiratory infectionRespiratory, thoracic and mediastinal disorders——
INCREASED FATIGUEPsychiatric disorders——
NECK PAINMusculoskeletal and connective tissue disorders——
Urinary tract infectionSkin and subcutaneous tissue disorders——
IRRITABILITYPsychiatric disorders——
WORSENING DEPRESSIONPsychiatric disorders——
DizzinessNervous system disorders——
INCREASED HEADACHESNervous system disorders——
FLU LIKE SYMPTOMS AFTER 2ND SHINGRIX VACCINERespiratory, thoracic and mediastinal disorders——
Acute SinusitisRespiratory, thoracic and mediastinal disorders——
Acute viral syndrome with ageusiaRespiratory, thoracic and mediastinal disorders——
Shortness of breathRespiratory, thoracic and mediastinal disorders——
Acute non-reccurrent frontal sinusitisRespiratory, thoracic and mediastinal disorders——
Sleep ApneaRespiratory, thoracic and mediastinal disorders——
Essential hypertensionCardiac disorders——
Type II diabetesEndocrine disorders——
NIGHT SWEATSEndocrine disorders——
Thyroid lobectomyEndocrine disorders——
Thyroid/neck nodule increasing in sizeEndocrine disorders——
Elevated liver function testBlood and lymphatic system disorders——
LeukopeniaBlood and lymphatic system disorders——
Worsening hypercholesterolemiaBlood and lymphatic system disorders——
Cold Sore, Right Upper LipInfections and infestations——
POSITIVE JCV INDEXInfections and infestations——
ShinglesInfections and infestations——
COVID InfectionInfections and infestations——
LOSS OF TONE/SORENESS, LEFT GLUTEUS MUSCLEMusculoskeletal and connective tissue disorders——
WORSENING OF LEG WEAKNESS, UPPER LEFT THIGH/QUAD, BILATERALMusculoskeletal and connective tissue disorders——
SLIGHT DECREASE IN HAND DEXTERITY, LEFTMusculoskeletal and connective tissue disorders——
LOW BACK PINCHING SENSATIONMusculoskeletal and connective tissue disorders——
BROKEN FINGER, LEFT HAND, 5TH FINGERMusculoskeletal and connective tissue disorders——
WEAKNESS, GENERALIZEDMusculoskeletal and connective tissue disorders——
Tenderness, left plantar surface of footMusculoskeletal and connective tissue disorders——
DUPUYTREN'S CONTRACTURE, BILATERAL HANDSMusculoskeletal and connective tissue disorders——
Back painMusculoskeletal and connective tissue disorders——
Right foot painMusculoskeletal and connective tissue disorders——
Pain, lower extremitiesMusculoskeletal and connective tissue disorders——
Weakness/tightness, lower extremitiesMusculoskeletal and connective tissue disorders——
Medial left knee painMusculoskeletal and connective tissue disorders——
RIGHT ANKLE TENDONITISMusculoskeletal and connective tissue disorders——

Most-reported serious reactions: Near-syncope, Pacemaker insertion, Heart block.

Data from ClinicalTrials.gov NCT03498131 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Melatonin Therapy Modulates Cerebral Metabolism and Enhances Remyelination by Increasing PDK4 in a Mouse Model of Multiple Sclerosis.
    Ghareghani M, Scavo L, Jand Y, Farhadi N, et al · · 2019 · cited 41× · PMID 30873027 · DOI 10.3389/fphar.2019.00147
  2. New insights in the mechanisms of impaired redox signaling and its interplay with inflammation and immunity in multiple sclerosis.
    Michaličková D, Šíma M, Slanař O. · · 2020 · cited 22× · PMID 31852206 · DOI 10.33549/physiolres.934276
  3. PDK4 Inhibition Ameliorates Melatonin Therapy by Modulating Cerebral Metabolism and Remyelination in an EAE Demyelinating Mouse Model of Multiple Sclerosis.
    Ghareghani M, Farhadi Z, Rivest S, Zibara K. · · 2022 · cited 10× · PMID 35355991 · DOI 10.3389/fimmu.2022.862316
  4. Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.
    Loeffler DA. · · 2024 · cited 8× · PMID 38875041 · DOI 10.3233/jad-240212
  5. Effect of Cellular Senescence in Disease Progression and Transplantation: Immune Cells and Solid Organs.
    Kirchner VA, Badshah JS, Hong SK, Martinez O, et al · · 2024 · cited 8× · PMID 37953486 · DOI 10.1097/tp.0000000000004838
  6. Impact of oral melatonin supplementation on urine and serum melatonin concentrations and quality-of-life measures in persons with relapsing multiple sclerosis.
    Smoot K, Gervasi-Follmar T, Marginean H, Chen C, et al · · 2024 · cited 2× · PMID 39126937 · DOI 10.1016/j.msard.2024.105799

Verify or expand the search:

Other recruiting trials for Relapsing Remitting Multiple Sclerosis

Currently open trials in the same condition.

Other Providence Health & Services trials

Trials by the same sponsor.

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Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing