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difficult recruitment and complete first visit in person during thne hight of tne pandemic and later not enough subjects
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Placebo Comparator | 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. |
|
| Melatonin | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Melatonin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Hospitalization | Number of COVID-19 related hospitalizations at 28 days | 28 days |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Margarita L Dubocovich, Ph.D. | University at Buffalo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University at Buffalo | Buffalo | New York | 14203 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31210428 | Background | Aliasgharzadeh A, Farhood B, Amini P, Saffar H, Motevaseli E, Rezapoor S, Nouruzi F, Shabeeb DH, Eleojo Musa A, Mohseni M, Moradi H, Najafi M. Melatonin Attenuates Upregulation of Duox1 and Duox2 and Protects against Lung Injury following Chest Irradiation in Rats. Cell J. 2019 Oct;21(3):236-242. doi: 10.22074/cellj.2019.6207. Epub 2019 Jun 15. | |
| 26692007 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | All participants who enrolled and took at least one dose of the medication/placebo | Posted | Count of Participants | Participants | 28 days |
|
Adverse event data was collected from Day 1 of enrollment to 6 weeks (42 days) after enrollment.
Information collected at each visit. In 2 participants who were hospitalized, information obtained from family. 2 participants were lost to follow up in spite of repeated attempts to contact them
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control | 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. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hospitalization | Infections and infestations | Systematic Assessment | COVID-19 progressed leading to hospitalization |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sanjay Sethi MD | University at Buffalo, SUNY | 7168884864 | ssethi@buffalo.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 23, 2021 | Sep 19, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D008550 | Melatonin |
| D008747 | Methylcellulose |
| D002214 | Capsules |
| ID | Term |
|---|---|
| D014363 | Tryptamines |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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placebo-controlled randomized double-blind pilot trial
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|
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| Placebo (Methylcellulose) capsule | Other | 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. |
|
|
| 28 days |
| 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. | 28 days |
| Mortality | 28-day mortality | 28 days |
| Andersen LP, Gogenur I, Rosenberg J, Reiter RJ. The Safety of Melatonin in Humans. Clin Drug Investig. 2016 Mar;36(3):169-75. doi: 10.1007/s40261-015-0368-5. |
| 30328031 | Background | Bazyar H, Gholinezhad H, Moradi L, Salehi P, Abadi F, Ravanbakhsh M, Zare Javid A. The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: a double-blind, placebo-controlled trial. Inflammopharmacology. 2019 Feb;27(1):67-76. doi: 10.1007/s10787-018-0539-0. Epub 2018 Oct 16. |
| 20964706 | Background | Chen CF, Wang D, Reiter RJ, Yeh DY. Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats. J Pineal Res. 2011 Jan;50(1):46-53. doi: 10.1111/j.1600-079X.2010.00808.x. Epub 2010 Oct 22. |
| 15919935 | Background | Cheung CY, Poon LL, Ng IH, Luk W, Sia SF, Wu MH, Chan KH, Yuen KY, Gordon S, Guan Y, Peiris JS. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J Virol. 2005 Jun;79(12):7819-26. doi: 10.1128/JVI.79.12.7819-7826.2005. |
| 31986264 | Background | Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. |
| 22377793 | Background | Kim JY, Lee YD, Kim BJ, Kim SP, Kim DH, Jo KJ, Lee SK, Lee KH, Baik HW. Melatonin improves inflammatory cytokine profiles in lung inflammation associated with sleep deprivation. Mol Med Rep. 2012 May;5(5):1281-4. doi: 10.3892/mmr.2012.814. Epub 2012 Feb 29. |
| 15860669 | Background | Law HK, Cheung CY, Ng HY, Sia SF, Chan YO, Luk W, Nicholls JM, Peiris JS, Lau YL. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood. 2005 Oct 1;106(7):2366-74. doi: 10.1182/blood-2004-10-4166. Epub 2005 Apr 28. |
| 18805959 | Background | Pedreira PR, Garcia-Prieto E, Parra D, Astudillo A, Diaz E, Taboada F, Albaiceta GM. Effects of melatonin in an experimental model of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L820-7. doi: 10.1152/ajplung.90211.2008. Epub 2008 Sep 19. |
| 29990691 | Background | Peng Z, Zhang W, Qiao J, He B. Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1beta in rats with COPD. Int Immunopharmacol. 2018 Sep;62:23-28. doi: 10.1016/j.intimp.2018.06.033. Epub 2018 Jun 30. |
| 30595364 | Background | Sanchez-Lopez AL, Ortiz GG, Pacheco-Moises FP, Mireles-Ramirez MA, Bitzer-Quintero OK, Delgado-Lara DLC, Ramirez-Jirano LJ, Velazquez-Brizuela IE. Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis. Arch Med Res. 2018 Aug;49(6):391-398. doi: 10.1016/j.arcmed.2018.12.004. Epub 2018 Dec 27. |
| 19567158 | Background | Shang Y, Xu SP, Wu Y, Jiang YX, Wu ZY, Yuan SY, Yao SL. Melatonin reduces acute lung injury in endotoxemic rats. Chin Med J (Engl). 2009 Jun 20;122(12):1388-93. |
| 25161126 | Background | Shin IS, Park JW, Shin NR, Jeon CM, Kwon OK, Kim JS, Kim JC, Oh SR, Ahn KS. Melatonin reduces airway inflammation in ovalbumin-induced asthma. Immunobiology. 2014 Dec;219(12):901-8. doi: 10.1016/j.imbio.2014.08.004. Epub 2014 Aug 10. |
| 30063115 | Background | Wang S, Zhao Z, Feng X, Cheng Z, Xiong Z, Wang T, Lin J, Zhang M, Hu J, Fan Y, Reiter RJ, Wang H, Sun D. Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition. J Cell Mol Med. 2018 Oct;22(10):5132-5144. doi: 10.1111/jcmm.13802. Epub 2018 Jul 31. |
| 32143642 | Background | Wu GC, Peng CK, Liao WI, Pao HP, Huang KL, Chu SJ. Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production. Respir Res. 2020 Mar 6;21(1):65. doi: 10.1186/s12931-020-1325-2. |
| 22609835 | Background | Wu WS, Chou MT, Chao CM, Chang CK, Lin MT, Chang CP. Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats. Acta Pharmacol Sin. 2012 Jun;33(6):775-82. doi: 10.1038/aps.2012.29. Epub 2012 May 21. |
| 29642520 | Background | Zhao X, Sun J, Su W, Shan H, Zhang B, Wang Y, Shabanova A, Shan H, Liang H. Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway. Int J Mol Sci. 2018 Apr 9;19(4):1118. doi: 10.3390/ijms19041118. |
| 32217117 | Background | Zhang R, Wang X, Ni L, Di X, Ma B, Niu S, Liu C, Reiter RJ. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020 Jun 1;250:117583. doi: 10.1016/j.lfs.2020.117583. Epub 2020 Mar 23. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | 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. 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. |
|
|
| Secondary | Hospitalization | Number of COVID-19 related hospitalizations at 28 days | Posted | Count of Participants | Participants | 28 days |
|
|
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| 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. | Posted | Number | participants | 28 days |
|
|
|
| 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. | 1 participant in each group was hospitalized and 1 was lost to follow up. | Posted | Mean | Standard Error | score on a scale | 28 days |
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| Secondary | Mortality | 28-day mortality | Posted | Count of Participants | Participants | 28 days |
|
|
|
| 0 |
| 3 |
| 1 |
| 3 |
| 0 |
| 3 |
| EG001 | 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. 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. | 0 | 5 | 1 | 5 | 0 | 5 |
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006571 | Heterocyclic Compounds |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D002482 | Cellulose |
| D005936 | Glucans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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