Melatonin for Multiple Sclerosis

Overseen By Tiffany Gervasi, MPH

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Providence Health & Services

Must be taking: Oral DMTs

Must not be taking: Melatonin, Steroids, Anticoagulants

Disqualifiers: Pregnancy, Cognitive disorders, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the potential benefits of melatonin for individuals with relapsing forms of multiple sclerosis (MS). Researchers aim to determine how melatonin might assist those who have maintained a stable oral disease-modifying therapy (DMT) for at least six months. Participants will receive a daily dose of either 3 mg or 5 mg of melatonin. Suitable candidates have relapsing MS and have consistently used a DMT without recent changes in sleep aids or Vitamin D doses. As an Early Phase 1 trial, this research seeks to understand how melatonin functions in people with MS, offering participants an opportunity to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current disease modifying therapy (DMT) for multiple sclerosis. You cannot add or change the dose of certain medications like sleep aids, Vitamin D, antidepressants, or stimulants within 30 days before or during the trial.

Is there any evidence suggesting that melatonin supplementation is likely to be safe for humans?

Research has shown that melatonin is generally safe for people. In studies comparing melatonin to a placebo (a harmless pill with no effect), only minor side effects appeared, such as headache, dizziness, nausea, and drowsiness, but these are not serious.

Melatonin has been used safely in various amounts. For example, studies found that administering 2 mg or 5 mg to children with certain conditions was safe. This suggests that the doses tested in this trial, 3 mg and 5 mg, are likely safe for adults as well.

Overall, melatonin does not present any special risks based on its safety record. It is not considered dangerous, and no special precautions are necessary. This information should reassure participants about its safety in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Multiple Sclerosis (MS), which often include immunosuppressants and disease-modifying therapies, melatonin offers a unique approach. Melatonin is a naturally occurring hormone that regulates sleep-wake cycles and has potential neuroprotective and anti-inflammatory effects, which could be beneficial in managing MS symptoms. Researchers are excited about melatonin because it has a different mechanism of action, focusing on reducing inflammation and oxidative stress, which may help slow disease progression. Additionally, melatonin is well-tolerated and has a favorable safety profile, making it a promising complementary option for individuals with MS.

What evidence suggests that melatonin supplementation could be effective for multiple sclerosis?

Research shows that melatonin might improve sleep, a common issue for people with multiple sclerosis (MS). In other conditions, studies have found that melatonin can help people sleep longer and better. For example, some studies found that children who took melatonin slept about an hour more than those who took a placebo. While direct proof that melatonin works for MS is lacking, better sleep might help manage MS symptoms. This trial will compare two different dosages of melatonin, 3 mg and 5 mg, to evaluate their effects on sleep in people with MS. These early findings suggest melatonin could be helpful, but more research is needed specifically for people with MS. ^{4 6 7 8 9}

Who Is on the Research Team?

Kyle Smoot, MD

Principal Investigator

Providence Health & Services

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 3 mg or 5 mg of melatonin daily for one year while continuing their stable dose of oral disease modifying therapy

12 months

Visits at Baseline, Month 3, Month 6, and Month 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Melatonin

How Is the Trial Designed?

Group I: 5 mg Melatonin Experimental Treatment 1 Intervention

Subjects will receive 5 mg melatonin once a day.

Group II: 3 mg Melatonin Experimental Treatment 1 Intervention

Subjects will receive 3 mg melatonin once a day.

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

Published Research Related to This Trial

Melatonin can effectively phase-shift circadian rhythms and improve sleep in totally blind individuals with non-24 hour sleep/wake disorder, especially when administered at the right time relative to their circadian phase.

Light exposure, particularly short wavelength light, can suppress melatonin production and influence circadian rhythms, indicating that optimizing light's spectral composition may enhance its effectiveness in regulating sleep patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of light and melatonin to phase-shift human circadian rhythms. Skene, DJ.[2019]

In a postmarketing surveillance study of 653 patients aged 55 and older, prolonged-release melatonin (PRM) significantly improved sleep quality from an average score of 4.2 to 2.6 and morning alertness from 4.0 to 2.5 over three weeks of treatment.

PRM demonstrated a low incidence of rebound insomnia (3.2% early withdrawal, 2.0% late withdrawal) and was well tolerated, with minimal adverse effects, suggesting it is a safe and effective alternative to traditional hypnotics for managing insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin. Hajak, G., Lemme, K., Zisapel, N.[2021]

Melatonin can help adults with delayed sleep phase disorder fall asleep earlier, but its use in children is concerning because it is not officially approved for them and lacks formal safety testing.

There are significant safety concerns regarding melatonin's effects on children's reproductive, cardiovascular, immune, and metabolic systems, as well as potential drug interactions, which have not been adequately studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential safety issues in the use of the hormone melatonin in paediatrics. Kennaway, DJ.[2015]

Melatonin effectively phase shifts circadian rhythms, making it a useful treatment for sleep disorders related to circadian misalignment, such as jet lag and shift work.

In specific conditions like delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake disorder, melatonin has been shown to advance sleep onset and improve overall sleep quality compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of melatonin in the treatment of phase shift and sleep disorders. Skene, DJ., Lockley, SW., Arendt, J.[2019]

In a 12-week trial involving 146 children with neurodevelopmental disorders, melatonin significantly reduced the time it took for children to fall asleep by an average of 37.5 minutes, while also increasing total sleep time by about 22.4 minutes according to parent-reported diaries.

While melatonin improved sleep onset, it resulted in earlier waking times and did not lead to significant improvements in child behavior or family functioning, indicating that while it is safe and tolerable, its overall impact on sleep quality may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial. Gringras, P., Gamble, C., Jones, AP., et al.[2022]

Melatonin can effectively improve sleep and adjust circadian rhythms when taken at the right times, helping with issues like jet lag and shift work, but its effectiveness is closely related to the timing and dosage.

While melatonin is generally safe for short-term use in healthy adults, there is a lack of long-term safety data, and its use should be carefully managed to avoid potential negative effects, especially with unregulated preparations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of circadian rhythm disorders--melatonin. Arendt, J., Deacon, S.[2019]

A systematic review of 50 studies on oral melatonin supplementation found that 26 studies reported no significant adverse events, indicating a generally favorable safety profile for melatonin, especially when used according to natural circadian rhythms.

While most adverse events were minor and manageable, some studies noted potential impacts on endocrine and cardiovascular functions, suggesting that dosage and timing are important factors to consider in melatonin use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with oral administration of melatonin: A critical systematic review of clinical evidence. Foley, HM., Steel, AE.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29096777/

Efficacy and Safety of Pediatric Prolonged-Release ... The rate of participants attaining clinically meaningful responses in TST and/or SL was significantly higher with PedPRM than with placebo (68.9% versus 39.3% ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8084705/

Sleep, Growth, and Puberty After 2 Years of Prolonged ... A recent 3-month double-blind, placebo-controlled study demonstrated efficacy and safety of pediatric prolonged-release melatonin (PedPRM) for insomnia in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0890856717316726

Efficacy and Safety of Pediatric Prolonged-Release ... The study met the primary endpoint: after 13 weeks of double-blind treatment, participants slept on average 57.5 minutes longer at night with PedPRM compared to ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04233502

Efficacy and Safety of Slenyto for Insomnia in Children With ... The main objective is to compare treatment effect of Slenyto® 2 mg or 5 mg to that of placebo on sleep duration (total sleep time [TST]) as assessed by the ...

5. liebertpub.com liebertpub.com/doi/10.1089/cap.2018.0020

Long-Term Efficacy and Safety of Pediatric Prolonged ... In the combined groups (Table 1), improvement was maintained or enhanced over the 39-week follow-up after attaining the optimal dose, with significant ...

6. ema.europa.eu ema.europa.eu/en/documents/product-information/circadin-epar-product-information_en.pdf

Circadin, INN-melatonin - European Medicines Agency Non-clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9842516/

Current Insights into the Risks of Using Melatonin as a ... In the analysis of safety data from randomized, placebo-controlled trials, minimal adverse effects were reported with both melatonin and placebo ...

8. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/14427m.pdf

Safety Data Sheet Melatonin is not classified as hazardous, with NFPA ratings of 0 for health, fire, and reactivity. No special handling or storage measures are ...

9. mayoclinic.org mayoclinic.org/drugs-supplements-melatonin/art-20363071

Melatonin Safety and side effects. Melatonin taken orally in appropriate amounts is generally safe. Melatonin can cause: Headache; Dizziness; Nausea; Drowsiness. Less ...