Dose-Ranging Study to Assess the Safety and Efficacy of Melatonin in Outpatients Infected With COVID-19

Sponsor

State University of New York at Buffalo (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04784754

Collaborator

National Center for Advancing Translational Science (NCATS) (NIH)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A pilot placebo-controlled randomized double-blind trial of Melatonin in outpatients with COVID-19 infection to evaluate Safety, Efficacy and Dose-ranging.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Melatonin Drug: Placebo	Phase 2

Detailed Description

Studies have shown in the blood of patients with COVID-19 there was a marked increase in the cytokines and chemokines interleukin 1β (IL-1β), interferon-γ (IFN-γ), interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1) and interleukin-4 (IL-4). Consequently, treatments that reduce cytokine/chemokine production that result in a less severe course of disease could be potentially beneficial. Melatonin, a pineal hormone, has been shown to have anti-inflammation, anti-oxidation and immune enhancing features. In multiple animal models of lung injury, Melatonin supplementation has been shown to decrease the number of inflammatory cells, reduce the levels of the cytokines IL-4, IL-5, IL-13 and TNF-a and reduce nitric oxide and hydroxyl radical concentrations. We propose a dose ranging pilot study to assess the safety and efficacy of melatonin in reducing hospitalization in COVID-19 patients with mild-moderate disease. A total of 50 participants will be randomized to the intervention arm (melatonin: 3 mg, or 30 mg three times a day for 14 days) or control arm (placebo) in a 2:2:1 fashion using a permuted block randomization scheme. Analyses will be performed with a focus on estimation of specific clinically important parameters, including safety and preliminary evidence of activity, for planning of a subsequent definitive comparative trial designed to fully assess efficacy.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Placebo-controlled randomized double-blind trialPlacebo-controlled randomized double-blind trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 1, 2021

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo capsules will be prepared using hypromellose capsules, filled using microcrystalline cellulose. This is the same excipient used in the preparation of the interventional drug. Placebo will be administered orally three times a day for 14 days in the same regimen used for the intervention.	Drug: Placebo Placebo capsules will be prepared using hypromellose capsules, filled using microcrystalline cellulose. This is the same excipient used in the preparation of the interventional drug. Placebo will be administered orally three times a day for 14 days in the same regimen used for the intervention. Other Names: Microcrystalline Cellulose
Experimental: Melatonin 3 mg Melatonin capsules will be prepared using hypromellose capsules containing 3 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days.	Drug: Melatonin Melatonin capsules will be prepared using hypromellose capsules containing 3 mg or 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days. Other Names: 5-methoxy-N-acetyl tryptamine
Experimental: Melatonin 30 mg Melatonin capsules will be prepared using hypromellose capsules containing 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days.	Drug: Melatonin Melatonin capsules will be prepared using hypromellose capsules containing 3 mg or 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days. Other Names: 5-methoxy-N-acetyl tryptamine

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo capsules will be prepared using hypromellose capsules, filled using microcrystalline cellulose. This is the same excipient used in the preparation of the interventional drug. Placebo will be administered orally three times a day for 14 days in the same regimen used for the intervention.

Drug: Placebo

Other Names:

Microcrystalline Cellulose

Experimental: Melatonin 3 mg

Melatonin capsules will be prepared using hypromellose capsules containing 3 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days.

Drug: Melatonin

Melatonin capsules will be prepared using hypromellose capsules containing 3 mg or 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days.

Other Names:

5-methoxy-N-acetyl tryptamine

Experimental: Melatonin 30 mg

Melatonin capsules will be prepared using hypromellose capsules containing 30 mg of the active component and identical excipient (Microcrystalline Cellulose) used in the placebo preparation. Melatonin will be administered orally three times a day for 14 days.

Drug: Melatonin

Other Names:

5-methoxy-N-acetyl tryptamine

Outcome Measures

Primary Outcome Measures

Cumulative Incidence of Treatment-Emergent Adverse Events [42 days]
Evaluate the incidence of serious adverse effects and discontinuation secondary to toxicity through 42 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).

Secondary Outcome Measures

Incidence of COVID-19 related hospitalization [42 days]
Incidence of COVID-19 related hospitalization at 42 days
COVID-19 related symptoms [42 days]
COVID-19 related symptoms as self-reported and on interview.
Rate of resolution of COVID-19 related symptoms [up to 42 days]
Change from baseline (day 1) as assessed to days 3, 7, 14, 28 and 42
Mortality [42 days]
42-day mortality

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
Positive testing for COVID-19 infection by standard RT-PCR assay or equivalent test.
Meets criteria for mild or moderate COVID-19 disease
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.
Subject can provide an emergency contact who the study team can contact in case the subject is not reachable on any of the study visits.

Exclusion Criteria:

Severe (eGFR<30 ml/min) and moderate (eGFR 30-60 ml/min) chronic kidney disease or requiring dialysis
Severe hepatic insufficiency defined as one or more of the following: Cirrhosis diagnosis, Serum ALT > 3x ULN or Alkaline phosphatase >3x ULN or bilirubin >2x ULN in the absence of Gilbert's or hemolysis, Uncontrolled acute or chronic liver disease (e.g. acute hepatitis A, unstable autoimmune hepatitis)
Pregnancy or breast feeding.
History of a seizure disorder.
Patient is taking Fluvoxamine, Capmatinib, Ciprofloxacin (Systemic), Deferasirox, Givosiran, Methoxsalen (Systemic), Mexiletine, Rucaparib, Stiripentol, Thiabendazole, Vemurafenib, Methoxsalen, Sodium oxybate or Echinacea.
Allergy to the study medication
Currently taking melatonin
Currently taking high dose (>500 mg/day) Vitamin C.
Meets criteria for Severe or Critical COVID-19