Safety and Efficacy of Melatonin in Outpatients Infected With COVID-19

Study Overview
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Brief Summary
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This study is a pilot randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of melatonin in adult outpatients suspected to be afflicted with COVID-19.

Detailed Description
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This study is a pilot randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of melatonin in outpatient adult patients suspected to be afflicted with COVID-19. Participants will be enrolled as outpatients within 72 hrs of onset of COVID-19 symptoms. The study will evaluate the safety of the intervention through 28 days of follow-up as compared to the control arm as assessed by cumulative incidence of serious adverse events (SAEs), cumulative incidence of Grade 3 and 4 adverse events (AEs), and/or discontinuation or temporary suspension of the investigational medication (for any reason). Additionally, the study will aim to evaluate the clinical efficacy of melatonin as compared to placebo as assessed by hospitalization, COVID-19 related symptoms and mortality. The ultimate goal is to determine in an adequately powered study if the anti-inflammatory and antioxidant actions of Melatonin can reduce the severity and prevent progression of COVID-19 when started in mild disease.

Official Title
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A Pilot Placebo-controlled Randomized Double-blind Trial of Melatonin in Outpatients With COVID-19 Infection

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Melatonin
* Other: Placebo (Methylcellulose) capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female adult ≥18 years of age at time of enrollment. Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study. Subject provides written informed consent prior to initiation of any study procedures. Understands and agrees to comply with planned study procedures. Agrees to the collection and storage of saliva samples per protocol. Exclusion Criteria: Severe chronic liver disease Severe chronic kidney disease or requiring dialysis Pregnancy or breast feeding. Allergy to the study medication Currently taking melatonin Currently taking high dose (>500 mg/day) Vitamin C

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: placebo-controlled randomized double-blind pilot trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Placebo capsules will be prepared with opaque gelatin capsules, filled using methylcellulose and over-encapsulated to appear identical to interventional drug. Placebo capsules will be given orally in the same regimen as intervention (three times daily for 14 days). Capsules will be prepared by the research pharmacist and will be mailed to study subjects directly by courier. Placebo capsules will be stored at room temperature. | Other: Placebo (Methylcellulose) capsule<br>* Placebo capsules will be prepared with opaque gelatin capsules, filled using methylcellulose and over-encapsulated to appear identical to interventional drug. Placebo capsules will be given orally in the same regimen as intervention (three times daily for 14 days). Capsules will be prepared by the research pharmacist and will be mailed to study subjects directly by courier. Placebo capsules will be stored at room temperature.<br>* Other names: Methylcellulose;|
| Experimental: Melatonin<br>Melatonin will be administered orally as a 10 mg dose three times a day for 14 days. Size 4 clear vegetable cellulose capsules containing 10 mg melatonin, microcrystalline cellulose, and rice concentrate prepared by Life Extension® will be over-encapsulated in opaque gelatin capsules. Over-encapsulation of melatonin treatments will be done by the research pharmacist and will be mailed to study subjects directly by courier. Melatonin capsules will be stored at room temperature. | Drug: Melatonin<br>* Melatonin will be administered orally as a 10 mg dose three times a day for 14 days. Size 4 clear vegetable cellulose capsules containing 10 mg melatonin, microcrystalline cellulose, and rice concentrate prepared by Life Extension® will be over-encapsulated in opaque gelatin capsules. Over-encapsulation of melatonin treatments will be done by the research pharmacist and will be mailed to study subjects directly by courier. Melatonin capsules will be stored at room temperature.<br>* Other names: 5-methoxy-N-acetyl tryptamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Incidence of Treatment-Emergent Adverse Events | Evaluate the incidence of serious adverse effects and discontinuation secondary to toxicity through 28 days of follow-up as compared to the control arm as assessed by: Cumulative incidence of serious adverse events (SAEs), Cumulative incidence of Grade 3 and 4 adverse events (AEs), Discontinuation or temporary suspension of the investigational medication (for any reason). | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalization | Incidence of COVID-19 related hospitalization at 28 days | 28 days | 
| COVID-19 related symptoms | COVID-19 related symptoms (Fever, chills, cough, nasal symptoms, body aches/muscle aches, headache, loss of smell, loss of taste, nausea, vomiting, diarrhea, fatigue, dizziness) that are self-reported and on interview. | 28 days | 
| Rate of resolution of COVID-19 related symptoms | Change from baseline (day 1) as assessed to days 3, 7, 14, and 28 | 28 days | 
| Mortality | 28-day mortality | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Melatonin, COVID-19