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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how sleep, body clocks, and melatonin (a sleep hormone) might influence the effectiveness of a flu vaccine. Participants will either take melatonin nightly or not, to determine its impact on their immune response to the vaccine. The trial aims to discover if improved sleep and melatonin use can enhance vaccine effectiveness. Suitable candidates have no allergies to the flu vaccine, no major immune or sleep disorders, and are not taking sleep or immune-related medications. As an unphased trial, this study provides participants the chance to contribute to understanding how lifestyle factors can enhance vaccine effectiveness.

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.

What prior data suggests that melatonin and the Phillips Actiwatch Spectrum Plus are safe for use in this study?

Research has shown that melatonin is generally safe for use. Studies have found it effective and safe for children and teens with sleep problems, especially those with autism or ADHD. However, less information exists about its long-term safety, particularly for certain groups like pregnant women. Despite this, many people tolerate melatonin well without major side effects. This suggests that melatonin is likely safe for most people, but some groups should exercise caution. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for enhancing vaccine response focus on boosting immune function through vaccines themselves or adjunct therapies like adjuvants. But melatonin stands out due to its antioxidant and anti-inflammatory properties, which may enhance the immune response. Researchers are excited about melatonin because it is a natural hormone with a well-known safety profile, unlike conventional pharmaceutical options. Moreover, its potential to improve sleep quality could indirectly boost immune function, offering a dual benefit. This makes melatonin a promising candidate for potentially improving vaccine efficacy with minimal side effects.

What evidence suggests that melatonin could be an effective treatment for flu vaccine response?

Research has shown that melatonin might enhance vaccine efficacy. In this trial, participants in the Melatonin Group will take 5mg of melatonin nightly to evaluate its effect on vaccine response. Studies have found that melatonin can improve the body's reaction to vaccines by influencing sleep and the body's internal clock. One study discovered that melatonin affects certain immune cells that aid the body's vaccine response. Another review suggests that by improving sleep, melatonin can indirectly boost vaccine effectiveness. Although more human research is needed, these findings offer hope that melatonin could enhance vaccine efficacy. ^{2 5 6 7 8}

Who Is on the Research Team?

Janine Danko, MD

Principal Investigator

Naval Medical Research Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11572083/

A randomized clinical trial of the impact of melatonin on ... Due to its role in sleep and circadian physiology, melatonin may further improve the efficacy of vaccines indirectly via known direct effects on sleep.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04953754

Study Details | NCT04953754 | Melatonin and Vaccine ... Many factors affect vaccine efficacy and host immunity. Sleep, circadian health and melatonin have been studied in the past to affect immune response to ...

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1663763/full

Exogenous Melatonin Boosts Vaccine-Induced Immunity in ... The data suggest that the melatonin has a selective modulatory effect on the antigen-specific cTfh subset response based on the levels of pre- ...

4. clinicaltrial.be clinicaltrial.be/en/details/76450?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Melatonin and Vaccine Response, Immunity ... Sleep, circadian health and melatonin have been studied in the past to affect immune response to vaccines and infection. Patient education about ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12389854/

A Narrative Review on How Timing Matters: Circadian and ... Very few studies reported data on clinical outcomes (Table 5), and these were mostly performed in the COVID-19 pandemic era. Evidence from COVID ...

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

Efficacy and Safety of Pediatric Prolonged-Release ... Conclusion: PedPRM was efficacious and safe for treatment of insomnia in children and adolescents with ASD with/without ADHD and NGD. The acceptability of this ...

7. withpower.com withpower.com/trial/phase-chronobiology-disorders-9-2021-329af

Melatonin for Vaccine Response (MAVRICS Trial) However, long-term safety data is limited, and caution is advised when using unlicensed preparations or in specific populations like pregnant women.

8. tandfonline.com tandfonline.com/doi/full/10.1080/14656566.2021.1959549

Pediatric prolonged-release melatonin for insomnia in ... Various medications were used 'off-label' despite limited efficacy and long-term safety data supporting their use in treating insomnia in children and ...