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

July 19, 2022 updated by: Margarita L. Dubocovich, PhD, State University of New York at Buffalo

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

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

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14203
        • University at Buffalo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or non-pregnant female adult ≥18 years of age at time of enrollment.
  2. Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study.
  3. Positive testing for COVID-19 infection by standard RT-PCR assay or equivalent test.
  4. Meets criteria for mild or moderate COVID-19 disease
  5. Subject provides written informed consent prior to initiation of any study procedures.
  6. Understands and agrees to comply with planned study procedures.
  7. Agrees to the collection and storage of saliva samples per protocol.
  8. 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:

  1. Severe (eGFR<30 ml/min) and moderate (eGFR 30-60 ml/min) chronic kidney disease or requiring dialysis
  2. 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)
  3. Pregnancy or breast feeding.
  4. History of a seizure disorder.
  5. Patient is taking Fluvoxamine, Capmatinib, Ciprofloxacin (Systemic), Deferasirox, Givosiran, Methoxsalen (Systemic), Mexiletine, Rucaparib, Stiripentol, Thiabendazole, Vemurafenib, Methoxsalen, Sodium oxybate or Echinacea.
  6. Allergy to the study medication
  7. Currently taking melatonin
  8. Currently taking high dose (>500 mg/day) Vitamin C.
  9. Meets criteria for Severe or Critical COVID-19

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative Incidence of Treatment-Emergent Adverse Events
Time Frame: 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).
42 days

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

State University of New York at Buffalo

Collaborators

National Center for Advancing Translational Sciences (NCATS)

Investigators

  • Principal Investigator: Margarita L Dubocovich, PhD, University at Buffalo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2021

Primary Completion (Anticipated)

September 30, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

February 22, 2021

First Submitted That Met QC Criteria

March 4, 2021

First Posted (Actual)

March 5, 2021

Study Record Updates

Last Update Posted (Actual)

July 22, 2022

Last Update Submitted That Met QC Criteria

July 19, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UBMELCOVID19-P
  • UL1TR001412 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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