Melatonin and Vaccine Response, Immunity, and Chronobiology Study

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the impact of sleep, circadian health and melatonin on flu vaccine immunogenicity.

Detailed Description
-----------------
Vaccination is critical to public health and disease prevention. However, despite the many scientific advancements and vaccines on the market, they are not always fully effective. Adjuvants are often used to boost immunity, but they are associated with more side effects, possible allergic reactions and public mistrust that supports vaccine hesitancy. Many factors affect vaccine efficacy and host immunity. Sleep, circadian health and melatonin have been studied in the past to affect immune response to vaccines and infection. Patient education about better sleep habits and/or melatonin use are potentially safe, cost effective, and accessible interventions that may improve host immunity and vaccine effectiveness. However, neither have been studied rigorously and at this time, are not actively implemented in the clinical arena. Hence, we propose a study comparing vaccine immunogenicity based on sleep quality, chronotype, and exogenous melatonin.

Official Title
-----------------
Melatonin and Vaccine Response, Immunity, and Chronobiology Study (MAVRICS): The Impact of Sleep, Circadian Health, and Melatonin on Vaccine Immunogenicity and Outcomes

Conditions
-----------------
Vaccine Response, Sleep, Circadian Rhythm Disorders

Intervention / Treatment
-----------------
* Dietary Supplement: Melatonin
* Device: Phillips Actiwatch Spectrum Plus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-64 Eligible to receive flu vaccination (at military hospital, DEERS eligible) Exclusion Criteria: Allergy or contraindication to getting flu vaccine Pregnancy or likelihood of getting pregnant in next few weeks Medical history of doctor diagnosed immune-compromising condition (HIV/AIDS, cancer, diabetes, significant cardiovascular disease) or doctor diagnosed sleep disorder (insomnia, narcolepsy).*Sleep apnea is an exclusion unless stable on treatment with cpap or oral device for more than3 months. Currently taking any immune suppressants or immunomodulating treatments (systemic corticosteroids, chemotherapy, etc, within the past 3 months) or sleep medication or supplement (including over the counter medications and melatonin, within the past 1 month).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective open label melatonin compared to control
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin Group<br>This group will get melatonin 5mg nightly | Dietary Supplement: Melatonin<br>* The melatonin group will receive 5mg melatonin nightly<br>Device: Phillips Actiwatch Spectrum Plus<br>* Both groups will be monitored by the FDA-cleared Actigraph<br>|
| Active Comparator: Control Group<br>This group will not get any treatment (melatonin) | Device: Phillips Actiwatch Spectrum Plus<br>* Both groups will be monitored by the FDA-cleared Actigraph<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-influenza antibody titers | Seroconversion and titer >=1:40 post-vaccination | 14-21 days post vaccination | 
| Cell-mediated immunity | ELISpot (secretion of Interferon-gamma and Granzyme B with restimulation by influenza viral antigens), Flow cytometry to determine CD4+ and CD8+ T cell producing IFN(g) with influenza viral restimulation, and Luminex multiplex cytokine analysis in cell culture supernatant of PBMC after restimulation with influenza viral antigens. | 14-21 days post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep survey - Pittsburgh Sleep Quality Index (PSQI) | PSQI and vaccine immunogenicity (primary outcomes) | 14-21 days post vaccination | 
| Actigraph data | Correlation of actigraph data and vaccine immunogenicity (primary outcomes) | 14-21 days post vaccination | 
| Chronotype survey - Munich ChronoType Questionaire (MCTQ) | Correlation of MCTQ score with vaccine immunity | 14-21 days post vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sleep, Circadian health, Vaccine immunogenicity, Melatonin