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

Phase 2

Terminated

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Control	Placebo (Methylcellulose) capsule	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.
Melatonin	Melatonin	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.

Primary Outcome Measures

Name	Time	Method
Number of Treatment-Emergent Adverse Events	28 days	Evaluate the number 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 number of serious adverse events (SAEs), Cumulative number of Grade 3 and 4 adverse events (AEs), Discontinuation or temporary suspension of the investigational medication (for any reason).

Secondary Outcome Measures

Name	Time	Method
COVID-19 Related Symptoms	28 days	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.
Hospitalization	28 days	Number of COVID-19 related hospitalizations at 28 days
Mortality	28 days	28-day mortality
Rate of Resolution of COVID-19 Related Symptoms	28 days	We designed a COVID-19 symptom scale. Participants rated 11 COVID related symptoms on a scale of 0-5. A maximum score of 55 would indicate the worst symptoms, while a score of 0 would indicate no symptoms. Change from baseline (day 1) in the total symptoms score was assessed on days 3, 7, 14, and 28.