COVID-19
Conditions
Keywords
Melatonin, COVID-19, SARS-CoV-2
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.
Interventions
DRUGMelatonin
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.
OTHERPlacebo (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.
Sponsors
State University of New York at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
placebo-controlled randomized double-blind pilot trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization | 28 days | Number of COVID-19 related hospitalizations at 28 days |
| 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. |
| 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. |
| Mortality | 28 days | 28-day mortality |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 3 |
| 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. | 5 |
| Total | 8 |
Baseline characteristics
| Characteristic | Melatonin | Total | Control |
|---|---|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 17.4 | 40.8 years STANDARD_DEVIATION 16.4 | 47.3 years STANDARD_DEVIATION 15.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 8 Participants | 3 Participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 0 / 3 | 0 / 5 |
| serious Total, serious adverse events | 1 / 3 | 1 / 5 |
Outcome results
Primary
Number of Treatment-Emergent Adverse Events
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).
Time frame: 28 days
Population: All participants who enrolled and took at least one dose of the medication/placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Number of Treatment-Emergent Adverse Events | 0 Participants |
| Melatonin | Number of Treatment-Emergent Adverse Events | 0 Participants |
Secondary
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.
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | COVID-19 Related Symptoms | 3 participants |
| Melatonin | COVID-19 Related Symptoms | 5 participants |
Secondary
Hospitalization
Number of COVID-19 related hospitalizations at 28 days
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Hospitalization | 1 Participants |
| Melatonin | Hospitalization | 1 Participants |
Secondary
Mortality
28-day mortality
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Mortality | 0 Participants |
| Melatonin | Mortality | 0 Participants |
Secondary
Rate of Resolution of COVID-19 Related Symptoms
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.
Time frame: 28 days
Population: 1 participant in each group was hospitalized and 1 was lost to follow up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Rate of Resolution of COVID-19 Related Symptoms | Visit 2 | 12 score on a scale | Standard Error 0 |
| Control | Rate of Resolution of COVID-19 Related Symptoms | Visit 4 | 8 score on a scale | — |
| Control | Rate of Resolution of COVID-19 Related Symptoms | Visit 3 | 10 score on a scale | — |
| Control | Rate of Resolution of COVID-19 Related Symptoms | Visit 5 | 5 score on a scale | — |
| Control | Rate of Resolution of COVID-19 Related Symptoms | baseline | 23.7 score on a scale | Standard Error 6.1 |
| Melatonin | Rate of Resolution of COVID-19 Related Symptoms | Visit 5 | 2 score on a scale | — |
| Melatonin | Rate of Resolution of COVID-19 Related Symptoms | baseline | 16.4 score on a scale | Standard Error 7.7 |
| Melatonin | Rate of Resolution of COVID-19 Related Symptoms | Visit 2 | 13.7 score on a scale | Standard Error 4.2 |
| Melatonin | Rate of Resolution of COVID-19 Related Symptoms | Visit 3 | 7.7 score on a scale | Standard Error 3.5 |
| Melatonin | Rate of Resolution of COVID-19 Related Symptoms | Visit 4 | 7.7 score on a scale | Standard Error 7.1 |