A Pilot Placebo-controlled Randomized Double-blind Trial of Melatonin in Outpatients With COVID-19 Infection
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Cumulative Incidence of Treatment-Emergent Adverse Events
研究概览
简要总结
A pilot placebo-controlled randomized double-blind trial of Melatonin in outpatients with COVID-19 infection to evaluate Safety, Efficacy and Dose-ranging.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
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.
干预措施: Melatonin (Drug)
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.
干预措施: Melatonin (Drug)
结局指标
主要结局
Cumulative Incidence of Treatment-Emergent Adverse Events
时间窗: 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).
次要结局
- Mortality(42 days)
- Incidence of COVID-19 related hospitalization(42 days)
- COVID-19 related symptoms(42 days)
- Rate of resolution of COVID-19 related symptoms(up to 42 days)
研究者
Margarita L. Dubocovich, PhD
SUNY Distinguished Professor
State University of New York at Buffalo