Melatonin for Vaccine Response

(MAVRICS Trial)

Overseen By Santina Maiolatesi

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Walter Reed National Military Medical Center

Must not be taking: Immune suppressants, Sleep medications

Disqualifiers: Pregnancy, Immune-compromising conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2-3 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will study if better sleep habits, understanding natural sleep cycles, and taking melatonin can help make the flu vaccine work better for people.

Will I have to stop taking my current medications?

Yes, if you are currently taking any immune suppressants, immunomodulating treatments, or sleep medications or supplements, you will need to stop. You must not have taken these medications within the past 3 months for immune treatments or the past 1 month for sleep aids.

Is melatonin safe for human use?

Melatonin, including formulations like Circadin and PedPRM, is generally considered safe for short-term use in humans, with studies showing no significant adverse effects compared to placebo. However, long-term safety data is limited, and caution is advised when using unlicensed preparations or in specific populations like pregnant women. ^{1 2 3 4 5}

How does melatonin differ from other drugs for enhancing vaccine response?

Melatonin is unique because it is a hormone that regulates sleep and circadian rhythms, and its use in enhancing vaccine response is novel compared to traditional treatments. Unlike other drugs, melatonin's potential benefits in this context may be related to its ability to modulate immune function through its effects on sleep and circadian regulation. ^{6 7 8 9 10}

Research Team

Janine Danko, MD

Principal Investigator

Naval Medical Research Center

Eligibility Criteria

This trial is for adults aged 18-64 who can get a flu shot at a military hospital and are registered in the DEERS system. It's not for those with allergies to the flu vaccine, pregnant women, or individuals with immune-compromising conditions like HIV/AIDS, cancer, diabetes, significant heart disease or diagnosed sleep disorders.

Inclusion Criteria

Eligible to receive flu vaccination at a military hospital and DEERS eligible

Exclusion Criteria

I have not taken immune suppressants, chemotherapy, or sleep aids in the past 3 months.

Allergy or contraindication to getting flu vaccine

Pregnancy or likelihood of getting pregnant in the next few weeks

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive melatonin 5mg nightly or no treatment (control group) to assess the impact on vaccine immunogenicity

2-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of anti-influenza antibody titers and cell-mediated immunity

2-3 weeks

Treatment Details

Interventions

• Melatonin
• Phillips Actiwatch Spectrum Plus

Trial Overview The study is looking into how sleep patterns and melatonin (a natural hormone) affect the body's response to the flu vaccine. Participants will be monitored using a Phillips Actiwatch Spectrum Plus device to track their sleep and activity rhythms.

Participant Groups

Group I: Melatonin Group Experimental Treatment 2 Interventions

This group will get melatonin 5mg nightly

Group II: Control Group Active Control 1 Intervention

This group will not get any treatment (melatonin)

Who Is Running the Clinical Trial?

Walter Reed National Military Medical Center

Lead Sponsor

Trials

149

Recruited

33,800+

Naval Medical Research Center

Collaborator

Trials

34

Recruited

2,900+

Findings from Research

Circadin, a prolonged-release melatonin formulation, effectively improves sleep quality and reduces sleep latency in patients aged 55 and over with primary insomnia, showing benefits in next-day alertness and overall quality of life.

Unlike traditional sedative hypnotics, Circadin does not impair cognitive or psychomotor skills, has no risk of dependence or abuse, and has a favorable safety profile with no significant adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs]. Zisapel, N.[2013]

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]

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]

Prolonged-release melatonin (Ped-PRM) has been approved as a pediatric treatment for insomnia in children and adolescents with autism spectrum disorder (ASD), showing safety for short-term use and no adverse effects on growth or development over the long term.

Melatonin is rapidly absorbed and metabolized, with immediate-release formulations being short-acting, while Ped-PRM provides sustained therapeutic levels throughout the night, highlighting the need for dose optimization due to variability in how individuals metabolize the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder. Zisapel, N.[2022]

Melatonin, particularly in the form of prolonged-release preparations like Circadin®, has been shown to improve sleep quality and reduce sleep latency in older adults, with a well-tolerated dosage of 2 mg once daily over 3 months.

Circadin® does not produce rebound effects or cognitive impairments commonly associated with traditional hypnotics, making it a safer first-line treatment option for insomnia in patients aged 55 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Melatonin: Physiological and pharmacological aspects related to sleep: The interest of a prolonged-release formulation (Circadin®) in insomnia]. Quera-Salva, MA., Claustrat, B.[2019]

Melatonin is a hormone that helps regulate sleep-wake cycles and has been used to treat various sleep disorders, including jet lag and insomnia.

Prolonged-release melatonin (Circadin) has recently been licensed in the UK specifically for treating primary insomnia, suggesting it may be an effective option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for primary insomnia? [2017]

References

1. Israel pubmed.ncbi.nlm.nih.gov

[Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs]. [2013]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

Prolonged-release melatonin for children with neurodevelopmental disorders. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[Melatonin: Physiological and pharmacological aspects related to sleep: The interest of a prolonged-release formulation (Circadin®) in insomnia]. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Role of the melatonin system in the control of sleep: therapeutic implications. [2021]

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

Melatonin and melatonergic drugs on sleep: possible mechanisms of action. [2022]

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

Role of melatonin in the regulation of human circadian rhythms and sleep. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Melatonin for primary insomnia? [2017]