Melatonin in Patients With Multiple Sclerosis (MS).

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

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing melatonin supplements in patients with relapsing multiple sclerosis who are already on stable treatments. The goal is to see if melatonin can improve their sleep and overall quality of life. Melatonin has been studied for its potential benefits in improving sleep quality and overall well-being in various conditions, including multiple sclerosis.

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 melatonin generally safe for human use?

Melatonin, including forms like Circadin and Slenyto, is generally considered safe for human use, with most adverse effects being minor and manageable, such as nausea, dizziness, and headaches. However, there are concerns about its effects on reproductive, cardiovascular, and metabolic systems, especially in children, and potential interactions with other medications. Long-term safety data is limited, so caution is advised, particularly with unlicensed preparations. ^{1 2 3 4 5}

How does this drug differ from other treatments for circadian rhythm disorders?

Melatonin is unique because it can shift human circadian rhythms by delaying them when taken in the morning and advancing them when taken in the afternoon or early evening. This makes it particularly effective for treating circadian rhythm disorders like jet lag and sleep issues related to shift work. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Melatonin, Circadin, Slenyto, PedPRM?

Research shows that melatonin can help adjust the body's internal clock, improving sleep and alertness in people with circadian rhythm disorders like jet lag and non-24-hour sleep-wake disorder, especially in blind individuals. ^{10 11 12 13 14}

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]

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 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]

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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Advances in the pharmacological management of non-24-h sleep-wake disorder. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Melatonin phase advances circadian rhythm. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Use of melatonin in the treatment of phase shift and sleep disorders. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Treatment of circadian rhythm disorders--melatonin. [2019]

9. Scotland pubmed.ncbi.nlm.nih.gov

Adverse events associated with oral administration of melatonin: A critical systematic review of clinical evidence. [2019]

10. Australia pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

The Mel1a melatonin receptor gene is expressed in human suprachiasmatic nuclei. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Genetic control of melatonin synthesis in the pineal gland of the mouse. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Melatonin: characteristics, concerns, and prospects. [2013]

14. England pubmed.ncbi.nlm.nih.gov

Melatonin shifts human circadian rhythms according to a phase-response curve. [2019]