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

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ClinicalTrials.gov Identifier: NCT04784754
Recruitment Status : Recruiting
First Posted : March 5, 2021
Last Update Posted : June 11, 2021
Sponsor:
Collaborator:
National Center for Advancing Translational Science (NCATS)
Information provided by (Responsible Party):
Margarita L. Dubocovich, PhD, State University of New York at Buffalo

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Placebo-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 : April 1, 2021
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 5-methoxy-N-acetyl tryptamine




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. Incidence of COVID-19 related hospitalization [ Time Frame: 42 days ]
    Incidence of COVID-19 related hospitalization at 42 days

  2. COVID-19 related symptoms [ Time Frame: 42 days ]
    COVID-19 related symptoms as self-reported and on interview.

  3. 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

  4. Mortality [ Time Frame: 42 days ]
    42-day mortality



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04784754


Contacts
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Contact: Margarita L Dubocovich, PhD 716 829 3048 mdubo@buffalo.edu
Contact: Sanjay Sethi, MD 716 888 4864 ssethi@buffalo.edu

Locations
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United States, New York
University at Buffalo Recruiting
Buffalo, New York, United States, 14203
Contact: Margarita Dubocovich, Ph.D.    716-829-3048    mdubo@buffalo.edu   
Contact: Sanjay Sethi, MD    (716) 888-4864    ssethi@buffalo.edu   
Sponsors and Collaborators
State University of New York at Buffalo
National Center for Advancing Translational Science (NCATS)
Investigators
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Principal Investigator: Margarita L Dubocovich, PhD University at Buffalo
Additional Information:
Publications:

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Responsible Party: Margarita L. Dubocovich, PhD, SUNY Distinguished Professor, State University of New York at Buffalo
ClinicalTrials.gov Identifier: NCT04784754    
Other Study ID Numbers: UBMELCOVID19-P
UL1TR001412 ( U.S. NIH Grant/Contract )
First Posted: March 5, 2021    Key Record Dates
Last Update Posted: June 11, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Margarita L. Dubocovich, PhD, State University of New York at Buffalo:
Melatonin
COVID-19
outpatient
SARS-CoV-2
Additional relevant MeSH terms:
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Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants