Clinical trial NCT04474483
Conditions: COVID-19
Keywords: Melatonin COVID-19 SARS-CoV-2
Sponsor: State University of New York at Buffalo
Start date: 2020-11-06; Completion date: 2022-07-22
Enrollment: 8 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: Melatonin intervention 2: Placebo (Methylcellulose) capsule
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol documents:
Prot_SAP_000.pdf: 
 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
Page 1 of 41 
 
Complete Research Protocol (HRP-503) 
 
Table of Contents 
Template Instructions ....................................................................................................... 2 
1.0 
Study Summary ........................................................................................................ 5 
2.0 
Objectives* .............................................................................................................. 6 
3.0 
Scientific Endpoints* ............................................................................................... 6 
4.0 
Background* ............................................................................................................ 7 
5.0 
Study Design* ........................................................................................................ 10 
6.0 
Study Intervention/Investigational Agent .............................................................. 10 
7.0 
Local Number of Subjects ..................................................................................... 11 
8.0 
Inclusion and Exclusion Criteria* .......................................................................... 11 
9.0 
Vulnerable Populations* ........................................................................................ 14 
10.0 Eligibility Screening* ............................................................................................ 15 
11.0 Recruitment Methods ............................................................................................. 15 
12.0 Procedures Involved*............................................................................................. 18 
13.0 Study Timelines* ................................................................................................... 20 
14.0 Setting .................................................................................................................... 21 
15.0 Community-Based Participatory Research ............................................................ 22 
16.0 Resources and Qualifications ................................................................................. 22 
17.0 Other Approvals ..................................................................................................... 24 
18.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 24 
19.0 Data Management and Analysis* .......................................................................... 25 
20.0 Confidentiality* ..................................................................................................... 26 
A. 
Confidentiality of Study Data ......................................................................... 27 
B. 
Confidentiality of Study Specimens ................................................................ 27 
21.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* ........................ 28 
22.0 Withdrawal of Subjects* ........................................................................................ 30 
23.0 Risks to Subjects* .................................................................................................. 31 
24.0 Potential Benefits to Subjects* .............................................................................. 32 
25.0 Compensation for Research-Related Injury ........................................................... 32 
26.0 Economic Burden to Subjects ................................................................................ 33 
27.0 Compensation for Participation ............................................................................. 33 
28.0 Consent Process ..................................................................................................... 33 
29.0 Waiver or Alteration of Consent Process ............................................................... 38 
30.0 Process to Document Consent ............................................................................... 38 
31.0 Multi-Site Research (Multisite/Multicenter Only)*............................................... 39 
32.0 Banking Data or Specimens for Future Use* ........................................................ 40 
 
 
 


 
Page 2 of 41 
IRB Version: 1/23/19 
Template Instructions 
Sections that do not apply: 
• In several sections, the addition of checkboxes for Not Applicable have been 
added to the template as responses.   
o If an N/A checkbox is present, select the appropriate justification 
from the list.   
o If an N/A checkbox is not present, or if none of the existing 
checkboxes apply to your study, you must write in your own 
justification. 
• In addition: 
o For research where the only study procedures are records/chart 
review:  Sections 19, 20, 22, 23, 24, 25, 31, and 32 do not apply. 
o For exempt research:  Sections 31 and 32 do not apply. 
 
Studies with multiple participant groups: 
 
• If this study involves multiple participant groups (e.g. parents and children), 
provide information in applicable sections for each participant group. Clearly 
label responses when they differ.  For example: 
Response Example 
Intervention Group:  
Control Group: 
Formatting: 
• Do not remove template instructions or section headings when they do not apply 
to your study. 
If you are pasting information from other documents using the “Merge Formatting” 
Paste option will maintain the formatting of the response boxes. 
Amendments: 
• When making modifications or revisions to this and other documents, use the 
Track Changes function in Microsoft Word. 
• Update the version date or number on Page 3. 
 
 


 
Page 3 of 41 
IRB Version: 1/23/19 
PROTOCOL TITLE: 
Include the full protocol title. 
Response: A pilot placebo-controlled randomized double-blind trial of Melatonin 
in outpatients with COVID infection. 
PRINCIPAL INVESTIGATOR: 
Name 
Department 
Telephone Number 
Email Address 
Response: Co-PIs 
Name: Margarita L. Dubocovich, Ph.D. 
Department:  Pharmacology and Toxicology (Suite 3212) 
Telephone Number: (716) 829-3048 / (716) 829-4719  
E-Mail: mdubo@buffalo.edu 
 
Name: Sanjay Sethi MD 
Department:  Medicine 
Telephone Number: (716) 888-4864  
E-Mail: ssethi@buffalo.edu 
 
VERSION NUMBER/DATE: 
Include the version number and date of this protocol. 
Response:  01-23-2021, version  8 
 
REVISION HISTORY 
 
Revision # 
Version 
Date 
Summary of Changes 
Consent 
Change? 
8/4/2020 
2 
 
yes 
9/24/2020 
3 
1. Addition of adverse events of special 
interest (depression and anxiety: 
addition of GAD-2 and PHQ-2 
questionnaires; and drowsiness: will be 
monitored by coordinator at visits, 
severity and timing will be recorded) 
2. Patient symptom logs will be collected 
through day 42 instead of through Day 
15 
3. Addition of external reviewer for 
outcomes, adverse events, SAEs to 
determine if drug or disease related. He 
yes 


 
Page 4 of 41 
IRB Version: 1/23/19 
will also if hospitalizations are COVID 
related.  External reviewer is Tom 
Russo MD.  He has been added to 
study team. 
4. Inclusion criteria: Must include 
emergency contact 
5. Exclusion criteria: define liver 
disorders specifically, was included 
prior but they wanted specific 
definitions 
6. Added Collection of WHO Clinical 
Progression Scale (0-10) through 
electronic medical records 
11/2/2020 
4 
Addition of protein to sample analysis 
 
11/5/2020 
5 
Added + test within 72 hrs in inclusion criteria, 
It was orginially supposed to be there but was 
left out of this section. 
 
11/16/2020 
6 
Changed courier deliver window from 15 and 
42 days to 15 ± 3 and 42 ± 3 days 
 
01/05/2021 
7 
Increased time of symptoms and positive test to 
within 5 days to increase enrollment 
 
01/15/2021 
8 
Addition of rapid antigen test for screening. 
Addition of social media advertising and other 
forms of advertising for recruitment. 
Addition of payment $50 per subject. 
Updated risks of Nasopharyngeal swabs.   
 
 
 
FUNDING: 
Indicate any funding for this proposal. This should match the Funding Sources 
page in Click IRB. 
Response: SUNY SEED 
GRANT APPLICABILITY: 
Indicate whether this protocol is funded by a grant (e.g. NIH, foundation grant).  
For a grant with multiple aims, indicate which aims are covered by this research 
proposal. 
NOTE: This question does not apply to studies funded by a sponsor contract. 
Include a copy of the grant proposal with your submission.     
Response: SUNY SEED 
 


 
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IRB Version: 1/23/19 
RESEARCH REPOSITORY: 
Indicate where the research files will be kept, including when the study has been 
closed.  The repository should include, at minimum, copies of IRB 
correspondence (approval, determination letters) as well as signed consent 
documents.  This documentation should be maintained for 3 years after the study 
has been closed.   
Response: All study approval documents and correspondence that is not stored in 
the Click System will be retained in the office of Dr. Margarita Dubocovich.  
Location: Jacobs School of Medicine and Biomedical Science, Suite 3212 
Address: 955 Main Street, Buffalo, NY 14203 
Department: Pharmacology and Toxicology 
1.0 Study Summary 
 
Study Title 
A pilot placebo-controlled randomized double-blind trial of 
Melatonin in outpatients with COVID infection. 
Study Design 
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.   
Primary Objective 
Evaluate the safety of the intervention 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).  
• Adverse Events of Special Interest 
• Discontinuation or temporary suspension of the 
investigational medication (for any reason).  
Secondary 
Objective(s) 
Evaluate the clinical efficacy of melatonin as compared to 
placebo as assessed by:  
 
Hospitalization   
Incidence of COVID related hospitalization at 42 days. Data 
will be obtained from electronic medical record.  
 
COVID related symptoms 
The speed of resolution of COVID related symptoms 
Change from baseline Day 1 to Day 42. 
Change in the WHO Clinical Progression Scale (0-10). Data 
will be obtained from electronic medical record.  
 
Mortality  
42-day mortality. Data will be obtained from electronic 
medical record. 


 
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IRB Version: 1/23/19 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
Melatonin (5-methoxy-N-acetyl tryptamine) 
IND/IDE #  
150700 
Study Population 
Outpatient adult (≥18 years old) patients with COVID-19.  
Sample Size 
30 subjects 
Study Duration for 
individual 
participants 
42 days 
Study Specific 
Abbreviations/ 
Definitions  
COVID-19: Coronavirus Disease 2019 
2.0 Objectives* 
2.1 Describe the purpose, specific aims, or objectives of this research. 
Response: The study is designed to evaluate the safety and efficacy of Melatonin.  
Participants will be enrolled as outpatients within 5 days of positive COVID-19 
test.  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 when started in mild disease.    
2.2 
State the hypotheses to be tested, if applicable. 
NOTE:  A hypothesis is a specific, testable prediction about what you expect to 
happen in your study that corresponds with your above listed objectives. 
Response: Melatonin reduces inflammation and oxidative stress in COVID-19 
patients reducing the severity of the disease. 
3.0 Scientific Endpoints* 
 
2.1    Describe the scientific endpoint(s), the main result or occurrence under 
study.   
 
NOTE:  Scientific endpoints are outcomes defined before the study begins to determine 
whether the objectives of the study have been met and to draw conclusions from the data.  
Include primary and secondary endpoints.  Some example endpoints are:  reduction of 
symptoms, improvement in quality of life, or survival.  Your response should not be a 
date.   
Response: 
Primary Objective  
Evaluate the safety of the intervention 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).  


 
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IRB Version: 1/23/19 
• 
Adverse Events of Special Interest 
• 
Discontinuation or temporary suspension of the investigational     
            medication (for any reason).  
Secondary Objectives  
Evaluate the clinical efficacy of melatonin as compared to placebo as assessed by: 
Hospitalization: Incidence of COVID related hospitalization at 42 days.   
Data will be obtained from electronic medical record.  
COVID related symptoms: Fever, chills, cough, nasal symptoms, body 
aches/muscle aches, headache, loss of smell, loss of taste, nausea, vomiting, 
diarrhea, fatigue, dizziness. The speed of resolution of COVID related symptoms. 
Change from baseline, Day 1 to Day 42.  Accessed by questionarre. 
Change in the WHO Clinical Progression Scale (0-10). Data will be obtained from 
electronic medical record.  
Mortality: 42-day mortality.  Data will be obtained from electronic 
medical record.  
Exploratory Objective   
Evaluate the effect of melatonin on virologic parameters as compared to placebo 
and assessed by:  
-Percent of subjects with SARS-CoV-2 detectable in saliva sample at days 1, 3, 7, 
14, 28 and 42.   
-Quantitative RT-PCR for SARS-CoV-2 virus in saliva sample at days 1, 3, 7, 14, 
28 and 42.   
-Evaluate the reduction in cytokine/chemokine RNA and/or protein levels in saliva: 
-Reduction as compared to baseline (Day 1) in salivary levels of 
cytokine/chemokine RNA and/or protein (IL-1, Il-2, IL-3, IL-4, IL-6, IL-8, IL-10, 
IL-11, IL-12, IL-13, Il-17, IL-18, TNF, IFNy, IFN, IFN-B, MCP1) at days 3, 7, 
14, and 28.   
4.0 Background* 
4.1 Provide the scientific or scholarly background, rationale, and significance 
of the research based on the existing literature and how it will contribute to 
existing knowledge.  Describe any gaps in current knowledge.  Include 
relevant preliminary findings or prior research by the investigator.  
Response: Overproduction of cytokines and chemokines is believed to contribute 
to the development in COVID-19 disease (Zhang et al. 2020; Law et al. 2005; 
Cheung et al. 2005).  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) (Huang et al. 2020; 
Zhang et al. 2020).  Currently, the overall cumulative hospitalization rate is 20.0 


 
Page 8 of 41 
IRB Version: 1/23/19 
per 100,000, with the highest rates in persons 65 years and older (63.8 per 100,000) 
and 50-64 years (32.8 per 100,000) (CDC 2020).  Therefore, the majority of 
COVID-19 positive patients are not hospitalized and may have a milder course of 
disease. Consequently, methods that reduce the increase in cytokines that may 
result in severe course of disease, is necessary. 
Melatonin, a pineal hormone, has been shown to have anti-inflammation, anti-
oxidation and immune enhancing features (Andersen, et al. 2016).  In multiple 
animal models of sepsis, acute lung injury, allergic asthma, respiratory syncytial 
virus (RSV) induced oxidative pulmonary injury, and ventilator-induced 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 (Peng et al. 2018; Shin 
et al. 2014; Pedreira et al. 2008; Kim et al. 2012; Wu et al. 2012; Wang et al. 2018; 
Zhao et al. 2018; Aliasgharzadeh et al. 2019; Wu et al. 2020; Shang et al. 2009; 
Chen et al. 2011).  In a randomized controlled trial, 8-week oral intake of 6 mg/d 
melatonin caused a significant decrease in serum levels of IL-6, TNF-α and C-
reactive protein in subjects with diabetes mellitus and periodontitis (Bazyar et al. 
2019).  A significant decrease in TNF-, IL-1b, IL-6, lipoperoxides and levels of 
nitric oxide catabolites occurred following oral administration of 25 mg/day 
melatonin for 6 months in subjects patients suffering from relapsing-remitting 
multiple sclerosis (Sanchez-Lopez et al. 2018).  A meta-analysis of 22 randomized 
controlled trials indicates that melatonin supplementation significantly reduces the 
levels of TNF-α and IL-6 (Bazyar et al. 2019).  Melatonin increases the 
proliferation and maturation of natural killer cells and other immune cells (Miller 
et al. 2006).  This evidence supports the use of melatonin as a supplement to reduce 
the levels of cytokines in COVID-19 patients (Zhang et al., 2020).  
4.2 Include complete citations or references.  
Response:  
Aliasgharzadeh, A., B. Farhood, P. Amini, H. Saffar, E. Motevaseli, S. Rezapoor, F. 
Nouruzi, D. H. Shabeeb, A. Eleojo Musa, M. Mohseni, H. Moradi, and M. Najafi. 2019. 
'Melatonin Attenuates Upregulation of Duox1 and Duox2 and Protects against Lung 
Injury following Chest Irradiation in Rats', Cell J, 21: 236-42. 
Andersen, L. P., I. Gogenur, J. Rosenberg and R. J. Reiter (2016). "The Safety of 
Melatonin in Humans." Clin Drug Investig 36(3): 169-175. 
Bazyar, H., H. Gholinezhad, L. Moradi, P. Salehi, F. Abadi, M. Ravanbakhsh, and A. 
Zare Javid. 2019. '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, 27: 67-76. 
CDC. 2020. 'Coronavirus Disease 2019 (COVID-19)'. 
https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html. 
Chen, C. F., D. Wang, R. J. Reiter, and D. Y. Yeh. 2011. 'Oral melatonin attenuates lung 
inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic 
fluid in rats', J Pineal Res, 50: 46-53. 


 
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IRB Version: 1/23/19 
Cheung, C. Y., L. L. Poon, I. H. Ng, W. Luk, S. F. Sia, M. H. Wu, K. H. Chan, K. Y. 
Yuen, S. Gordon, Y. Guan, and J. S. Peiris. 2005. 'Cytokine responses in severe acute 
respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to 
pathogenesis', J Virol, 79: 7819-26. 
Huang, C., Y. Wang, X. Li, L. Ren, J. Zhao, Y. Hu, L. Zhang, G. Fan, J. Xu, X. Gu, Z. 
Cheng, T. Yu, J. Xia, Y. Wei, W. Wu, X. Xie, W. Yin, H. Li, M. Liu, Y. Xiao, H. Gao, L. 
Guo, J. Xie, G. Wang, R. Jiang, Z. Gao, Q. Jin, J. Wang, and B. Cao. 2020. 'Clinical 
features of patients infected with 2019 novel coronavirus in Wuhan, China', Lancet, 395: 
497-506. 
Kim, J. Y., Y. D. Lee, B. J. Kim, S. P. Kim, D. H. Kim, K. J. Jo, S. K. Lee, K. H. Lee, 
and H. W. Baik. 2012. 'Melatonin improves inflammatory cytokine profiles in lung 
inflammation associated with sleep deprivation', Mol Med Rep, 5: 1281-4. 
Law, H. K., C. Y. Cheung, H. Y. Ng, S. F. Sia, Y. O. Chan, W. Luk, J. M. Nicholls, J. S. 
Peiris, and Y. L. Lau. 2005. 'Chemokine up-regulation in SARS-coronavirus-infected, 
monocyte-derived human dendritic cells', Blood, 106: 2366-74. 
Pedreira, P. R., E. Garcia-Prieto, D. Parra, A. Astudillo, E. Diaz, F. Taboada, and G. M. 
Albaiceta. 2008. 'Effects of melatonin in an experimental model of ventilator-induced 
lung injury', Am J Physiol Lung Cell Mol Physiol, 295: L820-7. 
Peng, Z., W. Zhang, J. Qiao, and B. He. 2018. 'Melatonin attenuates airway inflammation 
via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1beta in rats with 
COPD', Int Immunopharmacol, 62: 23-28. 
Sanchez-Lopez, A. L., G. G. Ortiz, F. P. Pacheco-Moises, M. A. Mireles-Ramirez, O. K. 
Bitzer-Quintero, D. L. C. Delgado-Lara, L. J. Ramirez-Jirano, and I. E. Velazquez-
Brizuela. 2018. 'Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and 
Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis', Arch Med Res, 49: 
391-98. 
Shang Y, Xu SP, Wu Y, Jiang YX, Wu ZY, Yuan SY, Yao SL. 2009. 'Melatonin reduces 
acute lung injury in endotoxemic rats.', Chin Med J (Engl). 122: 1388-93. 
Shin, I. S., J. W. Park, N. R. Shin, C. M. Jeon, O. K. Kwon, J. S. Kim, J. C. Kim, S. R. 
Oh, and K. S. Ahn. 2014. 'Melatonin reduces airway inflammation in ovalbumin-induced 
asthma', Immunobiology, 219: 901-8. 
Wang, S., Z. Zhao, X. Feng, Z. Cheng, Z. Xiong, T. Wang, J. Lin, M. Zhang, J. Hu, Y. 
Fan, R. J. Reiter, H. Wang, and D. Sun. 2018. 'Melatonin activates Parkin translocation 
and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 
inhibition', J Cell Mol Med, 22: 5132-44. 
Wu, G. C., C. K. Peng, W. I. Liao, H. P. Pao, K. L. Huang, and S. J. Chu. 2020. 
'Melatonin receptor agonist protects against acute lung injury induced by ventilator 
through up-regulation of IL-10 production', Respir Res, 21: 65. 
Wu, W. S., M. T. Chou, C. M. Chao, C. K. Chang, M. T. Lin, and C. P. Chang. 2012. 
'Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats', 
Acta Pharmacol Sin, 33: 775-82. 
Zhao, X., J. Sun, W. Su, H. Shan, B. Zhang, Y. Wang, A. Shabanova, H. Shan, and H. 
Liang. 2018. 'Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP 
Pathway', Int J Mol Sci, 19. 


 
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Zhang, R., X. Wang, L. Ni, X. Di, B. Ma, S. Niu, C. Liu, and R. J. Reiter. 2020. 'COVID-
19: Melatonin as a potential adjuvant treatment', Life Sci, 250: 117583. 
 
 
5.0 Study Design* 
5.1 Describe and explain the study design (e.g. case-control, cross-sectional, 
ethnographic, experimental, interventional, longitudinal, observational). 
Response: placebo-controlled randomized double-blind pilot trial 
6.0 
Study Intervention/Investigational Agent 
1.1 Description: Describe the study intervention and/or investigational 
agent (e.g., drug, device) that is being evaluated. 
Response: Melatonin (5-methoxy-N-acetyl tryptamine) 
6.1 Drug/Device Handling: If the research involves drugs or device, 
describe your plans to store, handle, and administer those drugs or 
devices so that they will be used only on subjects and be used only by 
authorized investigators. 
• 
If the control of the drugs or devices used in this protocol will 
be accomplished by following an established, approved 
organizational SOP (e.g., Research Pharmacy SOP for the 
Control of Investigational Drugs, etc.), please reference that 
SOP in this section. 
Response:  
Melatonin is a synthetic product with white physical appearance. Melatonin is sold 
as a food supplement for use in humans. This study will use Melatonin Tables (10 
mg per capsules) purchased from Life Extension (Northeast Fulfillment, Inc, 
Edison, NJ 08837) (see certificate of analysis attached) and shipped directly to 
research pharmacist and stored in the research pharmacy in the CRC. 
Melatonin will be administered as a 10 mg dose three times a day for 14 days.  
Capsules (size “4” Clear Vegetable cellulose capsule with off-white fill) containing 
10 mg melatonin, microcrystalline cellulose, and rice concentrate prepared by Life 
Extension® (Northeast Fulfillment, Inc, Edison, NJ 08837) will be over-
encapsulated in opaque gelatin capsules.  Placebo capsules will be prepared 
with identical opaque gelatin capsules using methylcellulose.  Both melatonin and 
placebo capsules will be given orally. Over-encapsulation of placebo and 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.  
Placebo capsules will be stored at room temperature. 


 
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IRB Version: 1/23/19 
6.2 If the drug is investigational (has an IND) or the device has an IDE 
or a claim of abbreviated IDE (non-significant risk device), include 
the following information: 
• 
Identify the holder of the IND/IDE/Abbreviated IDE. 
• 
Explain procedures followed to comply with sponsor 
requirements for FDA regulated research for the following: 
 
Applicable to: 
FDA Regulation 
IND Studies 
IDE studies 
Abbreviated 
IDE studies 
21 CFR 11 
X 
X 
 
21 CFR 54 
X 
X 
 
21 CFR 210 
X 
 
 
21 CFR 211 
X 
 
 
21 CFR 312 
X 
 
 
21 CFR 812 
 
X 
X 
21 CFR 820 
 
X 
 
Response: IND approved 
 
7.0 Local Number of Subjects 
7.1 Indicate the total number of subjects that will be enrolled or records that 
will be reviewed locally. 
Response: 30 
7.2 If applicable, indicate how many subjects you expect to screen to reach your 
target sample (i.e. your screen failure rate).  
Response: 60 
7.3 Justify the feasibility of recruiting the proposed number of eligible subjects 
within the anticipated recruitment period. For example, how many potential 
subjects do you have access to? What percentage of those potential subjects 
do you need to recruit? 
Response:  There are approximately 50 to 100 + COVID results reported daily in 
Erie County.  In addition, many more individuals with COVID symptoms do not 
get tested.  In order to to facilitate enrollment and determination of subject 
eligibility, those with symptoms of COVID-19 within 5 days that have not received 
a test or its result will be given a rapid antigen test to confirm eligibility for the 
study. 
 
8.0 Inclusion and Exclusion Criteria* 
8.1 Describe the criteria that define who will be included in your final study 
sample.  


 
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NOTE:  This may be done in bullet point fashion. 
Response:  
a.  Male or non-pregnant female adult ≥18 years of age at time of enrolment.  
b. Women of childbearing potential must agree to use at least one primary form of 
contraception for the duration of the study.  
c. Onset of COVID-19 Symptoms within 5 days 
d. Positive testing for COVID-19 infection by standard RT-PCR assay or equivalent 
test within 5 days or willingness to receive a rapid antigen test (EUA Nasal swab 
antigen test) by the study team. Follwing enrollment, among subjects that have not 
recieved a COVID test yet or its results, a nasopharyngeal swab sample will be 
obtained and a rapid antigen test (CareStart™ COVID-19 Antigen Test)  by the 
studyteam.  
e. Meets criteria for mild or moderate COVID disease defined as follows:  
Mild COVID-19  
• Symptoms of mild illness with COVID-19 that could include fever, cough, sore 
throat, malaise, headache, muscle pain, gastrointestinal symptoms, without 
shortness of breath or dyspnea    
• No clinical signs indicative of Moderate, Severe, or Critical Severity  
Moderate COVID-19  
• Symptoms of moderate illness with COVID-19, which could include any 
symptom of mild illness or shortness of breath with exertion  
• Clinical signs suggestive of moderate illness with COVID-19, such as respiratory 
rate ≥ 20 breaths per minute, saturation of oxygen (SpO2) > 93% on room air at sea 
level, heart rate ≥ 90 beats per minute.  
• No clinical signs indicative of Severe or Critical Illness Severity  
f. Subject provides written informed consent prior to initiation of any study 
procedures.  
g. Understands and agrees to comply with planned study procedures.  
h. Agrees to the collection and storage of saliva samples per protocol.  
i. Subject agrees to provide an emergency contact who the study team can contact in 
case the subject is not reachable on any of the study visits 
8.2 Describe the criteria that define who will be excluded from your final study 
sample.   
NOTE:  This may be done in bullet point fashion.  
Response:   
a. Severe chronic kidney disease (eGFR<30 ml/min) or Moderate renal impairment 
(eGFR 30-60 ml/min) or requiring dialysis 
b. 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) 
c. Pregnancy or breast feeding.  
d. History of a seizure disorder. 
e. Patient is taking Fluvoxamine, Capmatinib, Ciprofloxacin (Systemic), 


 
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Deferasirox, Givosiran, Methoxsalen (Systemic), Mexiletine, Rucaparib, 
Stiripentol, Thiabendazole, Vemurafenib, Methoxsalen, Sodium oxybate or 
Echinacea. 
f. Allergy to the study medication  
g. Currently taking melatonin  
h. Currently taking high dose (>500 mg/day) Vitamin C. 
i. Meets criteria for Severe or Critical COVID-19 infection defined as follows: 
Severe COVID-19  
• Symptoms suggestive of severe systemic illness with COVID-19, which could 
include any symptom of moderate illness or shortness of breath at rest, or 
respiratory distress  
• Clinical signs indicative of severe systemic illness with COVID-19, such as 
respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room 
air at sea level or PaO2/FiO2 < 300  
• No criteria for Critical Severity  
Critical Covid-19 
• Evidence of critical illness, defined by at least one of the following:  
– Respiratory failure defined based on resource utilization requiring at least one of 
the following:  
o Endotracheal intubation and mechanical ventilation, oxygen delivered 
by high-flow nasal cannula (heated, humidified, oxygen delivered via 
reinforced nasal cannula at flow rates > 20 L/min with fraction of 
delivered oxygen ≥ 0.5), noninvasive positive pressure ventilation, 
ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for 
one of the preceding therapies, but preceding therapies not able to be 
administered in setting of resource limitation) 
– Shock (defined by systolic blood pressure < 90 mm Hg, or diastolic blood 
pressure <60 mm Hg or requiring vasopressors)  
– Multi-organ dysfunction/failure  
8.3 Indicate specifically whether you will include any of the following special 
populations in your study using the checkboxes below.   
 
NOTE:  Members of special populations may not be targeted for enrollment in 
your study unless you indicate this in your inclusion criteria. 
Response:   
☐ 
Adults unable to consent 
☐ 
Individuals who are not yet adults (infants, children, teenagers) 
☐ 
Pregnant women 
☐ 
Prisoners 
 
8.4 Indicate whether you will include non-English speaking individuals in your 
study.  Provide justification if you will exclude non-English speaking 
individuals.  


 
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In order to meet one of the primary ethical principles of equitable selection 
of subjects, non-English speaking individuals may not be routinely excluded 
from research as a matter of convenience. 
In cases where the research is of therapeutic intent or is designed to 
investigate areas that would necessarily require certain populations who 
may not speak English, the researcher is required to make efforts to recruit 
and include non-English speaking individuals.  However, there are studies 
in which it would be reasonable to limit subjects to those who speak 
English.  Some examples include pilot studies, small unfunded studies with 
validated instruments not available in other languages, studies with 
numerous questionnaires, and some non-therapeutic studies which offer no 
direct benefit. 
Response:  Because of the pilot nature of this proposal with limited funding, we 
are not including non-English speaking individuals.  However, if this pilot project 
leads to a larger study, such subjects will be included.  
 
9.0 Vulnerable Populations* 
If the research involves special populations that are considered vulnerable, 
describe the safeguards included to protect their rights and welfare.   
NOTE: You should refer to the appropriate checklists, referenced below, to ensure you 
have provided adequate detail regarding safeguards and protections. You do not, 
however, need to provide these checklists to the IRB. 
9.1 For research that involves pregnant women, safeguards include: 
NOTE CHECKLIST: Pregnant Women (HRP-412) 
Response: 
  
☒ 
N/A:  This research does not involve pregnant women. 
9.2 For research that involves neonates of uncertain viability or non-viable 
neonates, safeguards include: 
NOTE CHECKLISTS: Non-Viable Neonates (HRP-413), or Neonates of Uncertain 
Viability (HRP-414) 
Response:  
 
☒ 
N/A:  This research does not involve non-viable neonates or neonates of 
uncertain viability. 
9.3 
For research that involves prisoners, safeguards include: 
NOTE CHECKLIST: Prisoners (HRP-415) 
Response:  
 
☒ 
N/A:  This research does not involve prisoners. 


 
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9.4 For research that involves persons who have not attained the legal age for 
consent to treatments or procedures involved in the research (“children”), 
safeguards include:   
NOTE CHECKLIST: Children (HRP-416) 
Response:  
 
☒ 
N/A:  This research does not involve persons who have not attained the 
legal age for consent to treatments or procedures (“children”). 
9.5 For research that involves cognitively impaired adults, safeguards include: 
NOTE CHECKLIST: Cognitively Impaired Adults (HRP-417) 
Response:  
 
☒ 
N/A:  This research does not involve cognitively impaired adults. 
9.6 Consider if other specifically targeted populations such as students, 
employees of a specific firm, or educationally or economically 
disadvantaged persons are vulnerable.  Provide information regarding 
their safeguards and protections, including safeguards to eliminate 
coercion or undue influence. 
Response: Not applicable as no population will be specifically targeted.  
 
10.0 
Eligibility Screening* 
10.1 Describe screening procedures for determining subjects’ eligibility.  
Screening refers to determining if prospective participants meet inclusion and 
exclusion criteria.  
Include all relevant screening documents with your submission (e.g. screening 
protocol, script, questionnaire).  
Response: Patients that have COVID-19 Symptoms within 5 days will be assessed 
for eligibility.  All screening procedures will take place entirely remotely by 
phone.  Screening will begin with a brief presentation about the study followed by 
a screening checklist. We will rely on patient’s statements over the phone to 
ensure they meet inclusion and exclusion criteria.  Individuals who meet the 
inclusion and exclusion criteria and are interested in participating in the study will 
then proceed to providing informed consent at the in person visit. Once consented, 
a subject that has not had a COVID-19 test will be given a rapid antigen test.  This 
test is done on a nasopharyngeal swab sample.   Those that test positive will 
continue in the study; those who test negative we be removed from the study.   
☐ 
N/A:  There is no screening as part of this protocol. 
11.0 
Recruitment Methods 
☐ 
N/A:  This is a records review only, and subjects will not be 
recruited.  NOTE:  If you select this option, please make sure that 


 
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all records review procedures and inclusion/exclusion screening 
are adequately described in other sections. 
11.1 Describe when, where, and how potential subjects will be recruited.  
NOTE:  Recruitment refers to how you are identifying potential participants and 
introducing them to the study.  Include specific methods you will use (e.g. 
searching charts for specific ICD code numbers, Research Participant Groups, 
posted advertisements, etc.). 
Response:  
It is anticipated that patients with COVID-19 will call their primary care physicians 
or present to emergency rooms. Recruitment efforts will include dissemination of 
information about this trial to these health care providers.  We will be sending a 
flyer for recruitment (submitted) to primary care practices, emergency rooms and 
urgent care centers in the area, such as UBMD primary care practices and Kaleida 
and ECMC emergency rooms.  The health care practitioners will provide potential 
participants the contact information for study staff.  Only potential participants who 
then contact the study staff will be enrolled in this study.   
 
We will be working with the Clinical and Translational Science Institute (CTSI) 
Community Engagement Team (CET) to create awareness of the study through their 
professional and community contacts. The tools they have available may include the 
Buffalo Research Registry (BRR, IRB Approved STUDY00000806), the Patient 
Voices Network (PVN), the Conventus CTSI/PVN and Evergreen Research Tables, 
and conducting outreach at various community events. These tools are methods by 
which the CET distributes IRB-approved recruitment information to community 
members.  
 
 We will also utilize the services of The CTSI Community Engagement Team (CET) 
to assist in participant recruitment.  
BUFFALO RESEARCH REGISTRY  
The Clinical and Translational Science Institute’s (CTSI) Community Engagement 
Team (CET) hosts the Buffalo Research Registry (BRR, IRB Approved 
STUDY00000806), a resource that connects researchers looking to recruit 
participants and community members looking to get involved with research. To 
participate in the registry, volunteers complete a voluntary intake form.  
Volunteers have agreed to be contacted about potential research opportunities based 
on their self-reported information.  
As described in the BRR’s IRB Approved Protocol (STUDY00000806), key 
personnel from the CTSI will serve as the conduit between our research team and 
the registry volunteers. Key personnel will verify our IRB study approval, review 
inclusion and exclusion criteria and will sort the registry data accordingly.  


 
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In terms of recruiting for our study, key personnel will pull volunteer reports using 
the inclusion and exclusion criteria. Key personnel will centrally invite volunteers 
to participate in the study and provide a warm hand off to our team.  
There are two ways we may share our study. These include:  
1. Electronically- Using the volunteer report from REDCap, key personnel from 
the CTSI will send initial e-mail invites to introduce our study to registry 
volunteers.  
2. Post Mail- Key personnel from the CTSI will provide our team with contact 
information (i.e. first name, last name, post mail address) to prepare a mailing. This 
information will be shared in a password protected excel spread sheet. The 
password to the spreadsheet will be sent in a separate follow-up e-mail.  
 
We will only use the list for this protocol and we agree to destroy the list once 
recruitment for the study has closed. We also plan on conducting follow-up by 
phone/email after initial contact. This contact information will be provided in a 
password protected excel spread sheet. The password to the spreadsheet will be 
sent in a separate follow-up e-mail. We will only use the list for this protocol and 
we agree to destroy the list once recruitment for the study has closed. We will have 
no access to the health information provided in the registry.  
The CET hosts the Buffalo Research Registry (BRR, IRB Approved 
STUDY00000806), a voluntary registry which can connect us to community 
members who have completed a health profile and are interested in participating in 
research. These community members have agreed to be contacted about potential 
research opportunities based on their self-reported information.  
COMMUNITY OUTREACH AND TABLING  
The CET also tables at many events in the community throughout the year and may 
display the IRB approved flyer for this project at their table at community events. 
Examples of events the CET attends include Good for the Neighborhood hosted by 
Independent Health Foundation, UB on the Green, Juneteenth, Elmwood Arts 
Festival and many others.  
The CET also hosts standing tables at the Conventus Building on the 4th floor of 
UBMD and at Evergreen where the IRB approved flyer can be made available to 
community members and patients. This will occur only after agreement between the 
CET and UBMD Conventus and/or Evergreen partners that the study is appropriate 
for the venue.  
Social Media Recruitment Plan 
This study will be shared via the social media platform Facebook. At this time no 
paid ads will be placed. A member of the study team member will contact social 
media managers and group/page administrators to request they post our Facebook 
post content to their public Facebook pages or private groups.  
 
 
 


 
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11.2 Describe how you will protect the privacy interests of prospective subjects 
during the recruitment process.   
NOTE:  Privacy refers to an individual’s right to control access to him or herself.   
Response: Prospective subjects control their own privacy interests as they will 
contact the research team if interested in participation.  Prospective subjects will 
be interviewed over the phone where the interviewer will be in a private room.   
 
11.3 Identify any materials that will be used to recruit subjects.  
NOTE:  Examples include scripts for telephone calls, in person announcements / 
presentations, email invitations.  
For advertisements, include the final copy of printed advertisements with your 
submission. When advertisements are taped for broadcast, attach the final 
audio/video tape.  NOTE:  You may submit the wording of the advertisement prior 
to taping to ensure there will be no IRB-required revisions, provided the IRB also 
reviews and approves the final version. 
Response: We will be sending a flyer for recruitment to primary care practices, 
emergency rooms and urgent care centers in the area. The same flyer will be 
posted on social media. A telephone script will be used when the participant calls 
the research team to introduce the study.  Both are submitted.  
 
12.0 
Procedures Involved* 
12.1 Provide a description of all research procedures or activities being 
performed and when they are performed once a subject is screened and 
determined to be eligible. Provide as much detail as possible.   
NOTE:  This should serve as a blueprint for your study and include enough detail 
so that another investigator could pick up your protocol and replicate the research.  
For studies that have multiple or complex visits or procedures, consider the 
addition of a schedule of events table in in your response. 
Response: Because of the highly contagious nature of COVID infection in the 
first few days after onset of symptoms, it is essential to minimize exposure of 
research team members to the subjects.  Therefore, except for the enrollment visit, 
all procedures for this study will be conducted remotely at the subject’s home.  
The Table below depicts all the research procedures.  
 
 
 
   
Screen  
Enrollment 
 
 
  
  
  
  
 
Day +/- Window  
−1 or 
1  
1  
  
Daily 
until 
Daily 
until 
Day 
3 ± 1 
Day 
7 ± 1 
Day 
14 ± 2 
Day 
28 ± 3  
Day 
42 ± 3 


 
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day 
14 
day 42 
Assessments/Procedures  
  
  
 
 
  
  
  
  
 
ELIGIBILTY  
  
  
 
 
  
  
  
  
 
Informed consent  
X  
  
 
 
  
  
  
  
 
Demographics & Medical 
History  
X  
  
 
 
  
  
  
  
 
Prior SARS-CoV-2 based 
on screening or perform 
rapid antigen testing  
X  
  
 
 
  
  
  
  
 
  
   
   
 
 
  
  
  
  
 
STUDY 
INTERVENTION  
  
  
 
 
  
  
  
  
 
Randomization  
  
X  
 
 
  
  
  
  
 
Administration of 
Melatonin/Placebo 
   
X 
X 
 
  
  
  
  
 
  
                              
 
 
  
  
  
  
 
STUDY PROCEDURES  
  
  
 
 
  
  
  
  
 
Body temperature 
  
X 
X 
X 
X 
X 
X 
X 
X 
Clinical data collection 
  
X 
X 
X 
X 
X 
X 
 X 
X 
Pulse Oximetry 
measurement 
 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event evaluation  
  
X  
 
 
X 
X 
X 
X  
X 
  
   
   
 
 
  
  
  
  
 
RESEARCH 
LABORATORY   
  
  
 
 
  
  
  
  
 
Saliva for PCR SARS-
CoV-2  
  
  
X 
 
 
X 
X 
X 
 X 
X 
Saliva for 
Cytokine/Chemokine 
RNA and/or protein 
  
X 
 
 
X 
X 
X 
X 
X 
 
Below is a day by day description of the study procedures. 
• 
For those subjects that have not had a COVID-test: Subjects will be enrolled and then tested 
for SARS-CoV2 using an EUA rapid antigen administered by the study team. If negative by 
rapid antigen test subjects will be withdrawn from study. Those subjects that have a prior 
positive test will not be give a rapid antigen test.  
• 
If COVID-19 positive: 
• 
Collect a baseline sample of saliva prior to taking drug, by spitting in a collection container 
that will be provided at time of consent. 
• 
Rate COVID symptoms before starting medication and then each day in the evening on a short 
questionnaire from Day 1 to Day 42. 
• 
Record body temperature and pulse oximetry each day in the morning and evening. 
• 
Take the IP 3 times a day orally for 14 days. 
• 
On Days 3, 7, 14, 28 and 42 collect a sample of saliva prior to taking drug in a collection 
container provided. Place the sample in a collection bag and place it in a freezer. 
• 
Speak to the research coordinator through telemedicine on Days 3, 7, 14, 28 and 42 to provide 


 
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data as well as any adverse effects of the treatment. These include anxiety and depression and 
drowsiness special interest adverse events.  The duration of these visits will be 15-30 minutes.  
• 
Allow a courier to come to your house to collect study related materials on Day 15 ± 3 and day 
43 ± 3 to pick up study related materials.  
12.2 Describe what data will be collected.   
NOTE:  For studies with multiple data collection points or long-term follow up, 
consider the addition of a schedule or table in your response. 
Response: Please see Table above 
 
12.3 List any instruments or measurement tools used to collect data 
(e.g. questionnaire, interview guide, validated instrument, data collection 
form).   
 
Include copies of these documents with your submission. 
Response: Included documents: 1) Data collection form (baseline); 2) Data 
collection form (Follow-up); 3) Daily symptom questionnaire; 4) Body 
temperature and pulse oximetry logs; 5) Instructions for saliva collection, storage 
and shipping 6) WHO Clinical Progression Scale 
12.4 Describe any source records that will be used to collect data about subjects 
(e.g. school records, electronic medical records). 
Response:  EMR data will be accessed to ascertain baseline health information 
and information relevant to the participants COVID illness. The study team will 
have remote access to the relevant EMRs.  
 
12.5 Indicate whether or not individual subject results, such as results of 
investigational diagnostic tests, genetic tests, or incidental findings will be 
shared with subjects or others (e.g., the subject’s primary care physician) 
and if so, describe how these will be shared. 
Response:  No 
 
12.6 Indicate whether or not study results will be shared with subjects or others, 
and if so, describe how these will be shared. 
Response: Study results will be posted on Clinical Trials.gov and submitted for 
publication in a peer reviewed journal.  
 
13.0 
Study Timelines* 
13.1 Describe the anticipated duration needed to enroll all study subjects. 
Response:  


 
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2 to 4 months 
13.2 Describe the duration of an individual subject’s participation in the study. 
Include length of study visits, and overall study follow-up time. 
Response: An individual subject will complete the study in about 42 days, from 
screening and enrollment at day -1 or 1 to follow-up on day 42 ± 3 days. After 
enrollment, there are a total of 5 telemedicine study visits. Each will last 
approximately 15-30 minutes.  
13.3 Describe the estimated duration for the investigators to complete this study 
(i.e. all data is collected and all analyses have been completed). 
Response:  
Up to 6 months 
14.0 
Setting 
14.1 Describe all facilities/sites where you will be conducting research 
procedures.  Include a description of the security and privacy of the 
facilities (e.g. locked facility, limited access, privacy barriers).  Facility, 
department, and type of room are relevant.  Do not abbreviate facility 
names.   
NOTE:  Examples of acceptable response may be:  “A classroom setting in the 
Department of Psychology equipped with a computer with relevant survey 
administration software,” “The angiogram suite at Buffalo General Medical 
Center, a fully accredited tertiary care institution within New York State with 
badge access,” or, “Community Center meeting hall.” 
Response: Because of the highly contagious nature of COVID infection in the first 
few days after onset of symptoms, it is essential to minimize exposure of research 
team members to the subjects.  Therefore, except for the enrollment visit, all 
procedures for this study will be conducted remotely at the subject’s home.  The 
interviewer will maintain privacy and security by ensuring their conversation 
cannot be overhead and that all study related documents are stored in a password 
protected folder with access limited to study personnel. The IP and matching 
placebo will be stored and distributed from the Research Pharmacy at the CRC.  
Study packages that contain daily symptom questionnaire, daily temperature and 
pulse oximetry logs, a thermometer, a pulse oximeter, saliva collection kits and 
return packaging will be assembled in the CRC by the research coordinator and be 
given to subject at the time of consent. We anticipate 2 courier visits to the 
participant’s homes.  On Day 15-17 to pick up saliva samples and questionnaires 
and unused IP and then on Day 29-31 to pick up the last saliva sample and unused 
study materials.   
14.2 For research conducted outside of UB and its affiliates, describe: 
• Site-specific regulations or customs affecting the research 
• Local scientific and ethical review structure 


 
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NOTE:  This question is referring to UB affiliated research taking place outside 
UB, i.e. research conducted in the community, school-based research, 
international research, etc.  It is not referring to multi-site research.  UB affiliated 
institutions include Kaleida Health, ECMC, and Roswell Park Cancer Institute.   
Response: NA 
 
☐ 
N/A:  This study is not conducted outside of UB or its affiliates. 
15.0 
Community-Based Participatory Research 
 
15.1 Describe involvement of the community in the design and conduct of the 
research.  
NOTE:  Community-Based Participatory Research (CBPR) is a collaborative 
approach to research that equitably involves all partners in the research process 
and recognizes the unique strengths that each brings.  CBPR begins with a 
research topic of importance to the community, has the aim of combining 
knowledge with action and achieving social change to improve health outcomes 
and eliminate health disparities. 
Response: NA 
 
☐ 
N/A:  This study does not utilize CBPR. 
15.2 
Describe the composition and involvement of a community advisory 
board. 
Response: NA 
 
☐ 
N/A:  This study does not have a community advisory board. 
16.0 
Resources and Qualifications 
16.1 Describe the qualifications (e.g., education, training, experience, expertise, 
or certifications) of the Principal Investigator and staff to perform the 
research.  When applicable describe their knowledge of the local study sites, 
culture, and society.  Provide enough information to convince the IRB that 
you have qualified staff for the proposed research.  
NOTE:  If you specify a person by name, a change to that person will require prior 
approval by the IRB.  If you specify a person by role (e.g., coordinator, research 
assistant, co-investigator, or pharmacist), a change to that person will not usually 
require prior approval by the IRB, provided that the person meets the 
qualifications described to fulfill their roles. 
Response:     
Co-PI: Margarita L. Dubocovich, PhD is a SUNY Distinguished 
Professor in the Department of Pharmacology and Toxicology in Jacobs 


 
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School of Medicine and Biomedical Sciences.  She is also Senior Associate 
Dean for Diversity and Inclusion.  She has over 30 years of experience 
studying melatonin and melatonin receptors. 
Co-PI: Sanjay Sethi MD, is a Professor of Medicine and Chief of the 
Division or Pulmonary and Critical Care Medicine in Jacobs School of 
Medicine and Biomedical Sciences.  He is also the Medical Director of the 
Clinical Research Office. He has expertise in pulmonary diseases including 
chronic obstructive pulmonary disease (COPD). 
Co-I: Gregory Wilding PhD is the Professor and Chair of the Department 
of Biostatistics in the School of Public Health and Health Professions 
(SPHHP). He has expertise in the design and analysis of clinical studies and 
have participated in many aspects of clinical and non-clinical research. 
Co-I: Jessica L. Reynolds PhD is an Associate Professor of Medicine in 
Jacobs School of Medicine and Biomedical Sciences.  She has expertise in 
Immunology and Infectious Disease. 
External Reviewer: Thomas Russo MD, an infectious disease specialist at 
University of Buffalo will serve as an external reviewer for the outcomes 
collected in this study.  Specifically, he will adjudicate whether the 
adverse events (grade 3 or 4) and SAEs collected are drug or disease 
related.  He will also adjudicate whether the hospitalizations observed in 
this study were COVID related or not.  These adjudications will be on 
blinded data.   
Research Pharmacist:  Denise Swiatek PharmD is the designated research 
pharmacist at the Clinical Research Center in the UB CTRC building.  
Research Coordinator: To be hired. 
 
Describe other resources available to conduct the research.  
16.2 Describe the time and effort that the Principal Investigator and research 
staff will devote to conducting and completing the research. 
NOTE:  Examples include the percentage of Full Time Equivalents (FTE), hours 
per week.  The question will elicit whether there are appropriate resources to 
conduct the research. 
Response:  
Margarita L. Dubocovich, PhD 0.05 FTE 
Sanjay Sethi MD 0.05 FTE 
Gregory Wilding PhD 0.05 FTE 
Jessica L. Reynolds PhD 0.05 FTE 
Thomas Russo MD 0.05 FTE 
 


 
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16.3 Describe the availability of medical or psychological resources that subjects 
might need as a result of anticipated consequences of the human research, if 
applicable. 
NOTE:  One example includes: on-call availability of a counselor or psychologist 
for a study that screens subjects for depression. 
Response: If a research staff determines that the participant needs additional 
medical or psychological resources during the course of the study, they will ask 
the participant to contact their primary care practitioner in non-emergent situation 
or to go the Emergency Department in emergent situations.   
 
16.4 Describe your process to ensure that all persons assisting with the research 
are adequately informed about the protocol, the research procedures, and 
their duties and functions. 
Response:  The co-PIs of this study will assign the research team members the 
research related duties and ensure that they are adequately trained to perform the 
duties.  Any amendments to the study protocol and any events that alter the risk-
benefit ratio of the study will be promptly communicated to the team members.  
17.0 
Other Approvals 
17.1 Describe any approvals that will be obtained prior to commencing the 
research (e.g., school, external site, funding agency, laboratory, radiation 
safety, or biosafety). 
Response:  
 
☒ 
N/A:  This study does not require any other approvals. 
18.0 
Provisions to Protect the Privacy Interests of Subjects 
18.1 Describe how you will protect subjects’ privacy interests during the course 
of this research. 
NOTE:  Privacy refers to an individual’s right to control access to him or herself.  
Privacy applies to the person.  Confidentiality refers to how data collected about 
individuals for the research will be protected by the researcher from release.  
Confidentiality applies to the data.   
Examples of appropriate responses include:  “participant only meets with a study 
coordinator in a classroom setting where no one can overhear”, or “the 
participant is reminded that they are free to refuse to answer any questions that 
they do not feel comfortable answering.”   
Response:  
Prospective subjects will be interviewed over the phone where the interviewer 
will be in a private room.  Subjects will be at their residence or place of work.  


 
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18.2 Indicate how the research team is permitted to access any sources of 
information about the subjects.   
NOTE:  Examples of appropriate responses include:  school permission for review 
of records, consent of the subject, HIPAA waiver.  This question does apply to 
records reviews. 
Response: HIPAA waiver. Consent of the participants. 
 
19.0 
Data Management and Analysis* 
19.1 Describe the data analysis plan, including any statistical procedures.  This 
section applies to both quantitative and qualitative analysis.  
Response:   
Randomization: Participants will be randomized to the intervention or control arm 
in a 2:1 fashion using a permuted block randomization scheme. The randomization 
lists to be used in this study will be generated by the study biostatistician. Subjects 
will be included in data analyses according to their randomized assignment 
irrespective of the treatment actually received (intent-to-treat).  
Missing data: The amount and nature of missing data will be characterized and no 
method of imputation will be used for missing data. We acknowledge the possibility 
of informative missingness with some of the outcomes, that is, the probability of a 
particular observation being missing may be related to the health or death of a 
subject, and therefore analyses will be interpreted with caution. 
Accrual: Participants will be accrued to the study on a first-come basis. The 
projected accrual is approximately 15 per month, and therefore recruitment is 
expected to be complete at most 60 days following the study starting point. Subjects 
will be followed for 1 month after recruitment completion, so total study duration 
will be approximately 3 months. During the enrollment period, the study 
biostatistician will model and predict accrual rates in order to verify adequacy of 
the enrollment process. 
Descriptive analyses: Measured outcome variables will be summarized overall 
and by relevant demographic and baseline variables. Descriptive statistics such as 
frequencies and relative frequencies will be computed for all categorical variables. 
Numeric variables will be summarized using simple descriptive statistics such as 
the mean, standard deviation and range. A variety of graphical techniques will also 
be used to display data, ex., histograms, boxplots, scatterplots, etc.   
Statistical analyses: Analyses will be performed with a focus on estimation of 
specific clinically important parameters, including preliminary evidence of safety 
and activity of the intervention, for use in the planning of subsequent comparative 
trials designed to fully assess safety and efficacy. The primary outcomes in the 
examination of the study intervention, specifically, the cumulative incidence of 
serious adverse events (SAEs), the cumulative incidence of Grade 3 and 4 adverse 
events (AEs), and the discontinuation or temporary suspension of the 
investigational medication (for any reason), are measured in a binary fashion at the 


 
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study participant-level. The corresponding probabilities will each be estimated 
using the relative frequency. In addition to the point estimates based on collected 
data, 95% confidence intervals will also be computed based on the methodology of 
Clopper and Pearson. Additional binary study outcomes, ex., incidence of COVID-
related hospitalization and hospitalization for any reason, will be analyzed in an 
identical fashion. Comparison between randomized groups with regards to these 
outcomes will be done using Fisher’s exact test. For numeric outcomes, such as 
symptom questionnaire results and measures of clinical improvement, the rank-
based Wilcox rank sum test will be used to compare groups. For outcomes which 
may be subject to censoring such as speed of resolution of COVID related 
symptoms, parameter estimation will be based on the Kaplan-Meier estimator and 
the log-rank test will be utilized to compare groups, Proposed exploratory outcomes 
are collected longitudinally. Proposed exploratory outcomes are collected 
longitudinally. Standard statistical techniques for the analysis of such outcomes, 
ex., mixed linear models, will be utilized. Although primary analyses will be 
performed based on the intent-to-treat principle, to evaluate the robustness of these 
results, analyses will also be conducted in a secondary fashion based on actual 
treatment received. All statistical tests will be two-sided and tested at a 0.05 
nominal significance level. All analyses will be carried out using SAS version 9.4 
(or higher) statistical software (Cary, NC).   
19.2 If applicable, provide a power analysis.   
NOTE:  This may not apply to certain types of studies, including chart/records 
reviews, survey studies, or observational studies.  This question is asked to elicit 
whether the investigator has an adequate sample size to achieve the study 
objectives and justify a conclusion.  
Response:  
Sample size justification: In that accurate assessment of the safety of the study 
intervention is of utmost importance in this study, the samples size of 20 in the 
intervention group is based on the expected precision associated with our estimated 
safety probabilities corresponding to the primary outcomes expressed in terms of 
confidence interval width. Note that a true probability of 0.5 represents the 
mathematically worst-case scenario with in regards to precision and therefore we 
may take precision at that point to be an upper bound of expected accuracy. We see 
that with a sample size of 20 participants the standard error of these estimators will 
be at most 11 percentage points.   
 
19.3 Describe any procedures that will be used for quality control of collected 
data. 
Response: Collected data will be reviewed by the co-PIs on a weekly basis to 
ensure adequate data collection. 
 
20.0 
Confidentiality* 
 


 
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A. Confidentiality of Study Data 
 
Describe the local procedures for maintenance of confidentiality of study data 
and any records that will be reviewed for data collection.   
 
20.1 
A.  Where and how will all data and records be stored?  Include 
information about:  password protection, encryption, physical controls, 
authorization of access, and separation of identifiers and data, as applicable.  
Include physical (e.g. paper) and electronic files. 
Response:  
Identifiers will be collected on the Demographics page of the Baseline form.  This 
form will be kept in a locked cabinet in the PI’s office.  This form will contain the 
Study subject ID number and their initials.  All subsequent forms will only contain 
the Subject Study ID number and their initials.   
Subjects will be asked to provide personal health information (PHI). All attempts 
will be made to keep this PHI confidential within the limits of the law. However, 
there is a chance that unauthorized persons will see the subject’s PHI. All study 
records will be kept in a locked file cabinet in the PIs office. Electronic files will 
be password protected.   
Any publications from this trial will not use information that will identify subjects 
by name. Organizations that may inspect and/or copy research records maintained 
at the participating site for quality assurance and data analysis include groups 
such as the IRB, Sponsor and the pertinent regulatory authorities.  
20.2 
A.  How long will the data be stored? 
Response: Data will be stored for the duration of this study and up to ten years 
after procurement.  
20.3 
A.  Who will have access to the data? 
Response: Only members of the PI’s research team will have access to the data 
obtained from participants.  De-identified data will be made available to the 
broader scientific public per FDA policy.   
20.4 
A.  Who is responsible for receipt or transmission of the data? 
Response:  The co-PIs are responsible.  
 
20.5 
A.  How will the data be transported? 
Response: The paper data collection forms will be transported by the research 
personnel in subject specific manila folders to the PIs office where they will be 
stored under lock and key.  
B. Confidentiality of Study Specimens 
 


 
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Describe the local procedures for maintenance of confidentiality of study 
specimens.   
 
☐ 
N/A:  No specimens will be collected or analyzed in this research.   
(Skip to Section 19.0) 
 
20.6 
B.  Where and how will all specimens be stored?  Include information 
about:  physical controls, authorization of access, and labeling of specimens, as 
applicable.   
Response: Specimens will be stored in -80°C freezers in the laboratory of the Co-I 
in the Clinical and Translational Research Center where access is restricted to 
building employees only. Specimens labels will only have the study subject 
number and therefore will be coded.  
20.7 
B.  How long will the specimens be stored? 
Response: All coded specimens will be stored for the duration of this study and up 
to ten years after procurement.   
 
20.8 
B.  Who will have access to the specimens? 
Response: Only members of the PI’s research team will have access to the 
specimens obtained from participants.   
 
20.9 
B.  Who is responsible for receipt or transmission of the specimens? 
Response: Saliva specimens collected up to Day 28 will be transported by courier 
to the CTRC and received by Dr. Reynolds, the co-I.  
 
20.10 B.  How will the specimens be transported? 
Response: 
Saliva Specimens will be transported from the subject’s home to the CTRC by 
Courier.  The subject will be instructed to place the collected saliva specimens in 
a biohazard bag and then store them in their home refrigerator/freezer.  The 
specimens will be provided to the courier who will bring them to the laboratory in 
a thermacol box that contains ice pack or dry ice.   
 
21.0 
Provisions to Monitor the Data to Ensure the Safety of 
Subjects* 
☐ 
N/A:  This study is not enrolling subjects, or is limited to records review 
procedures only.  This section does not apply. 
 


 
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NOTE:  Minimal risk studies may be required to monitor subject safety if the research 
procedures include procedures that present unique risks to subjects that require 
monitoring.  Some examples include:  exercising to exertion, or instruments that elicit 
suicidality or substance abuse behavior.  In such cases, N/A is not an acceptable 
response. 
 
21.1 Describe the plan to periodically evaluate the data collected regarding both 
harms and benefits to determine whether subjects remain safe. 
Response: On a weekly basis the co-PIs will review the data being collected to 
determine if there are any worrisome patterns of the adverse events (grade 3 or 4) 
and SAEs reported.  This review will be blinded.  We do anticipate a 20% rate of 
hospitalization in our subjects.  Therefore, only if the rate is much higher than that 
will there be a cause of concern.   
 
21.2 Describe what data are reviewed, including safety data, untoward events, 
and efficacy data. 
Response: All safety data will be reviewed.  
External Review of Data 
Thomas Russo MD, an infectious disease specialist at University of Buffalo will 
serve as an external reviewer for the outcomes collected in this study.  
Specifically, he will adjudicate whether the adverse events (grade 3 or 4) and 
SAEs collected are drug or disease related.  He will also adjudicate whether the 
hospitalizations observed in this study were COVID related or not.  These 
adjudications will be on blinded data.   
 
 
 
21.3 Describe any safety endpoints. 
• 
Response: Cumulative incidence of serious adverse events (SAEs)   
• 
Cumulative incidence of Grade 3 and 4 adverse events (AEs).  
• 
Adverse effects of special interest: Anxiety and Depression (GAD-
2 and PHQ-2 questionnaires); Drowsiness (will be recorded) 
• 
Discontinuation or temporary suspension of the investigational     
medication (for any reason). 
 
21.4 Describe how the safety information will be collected (e.g., with case report 
forms, at study visits, by telephone calls with participants). 
Response:  The safety information will be collected by scheduled phone calls as 
described above.  


 
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21.5 Describe the frequency of safety data collection. 
Response: Days 1, 3, 7, 14, 28 and 42 
 
21.6 Describe who will review the safety data. 
Response: The co-PIs will review the data along with the biostatistician Dr. 
Wilding.  
 
21.7 Describe the frequency or periodicity of review of cumulative safety data. 
Response: Weekly 
 
21.8 Describe the statistical tests for analyzing the safety data to determine 
whether harm is occurring. 
Response:  As the number of participants is small and data is blinded, formal 
statistical testing will not be used.  
 
21.9 Describe any conditions that trigger an immediate suspension of the 
research. 
Response: A hospitalization rate that is much larger than the anticipated 20%.  A 
high incidence of adverse events that can be potentially attributed to Melatonin.  
 
22.0 
Withdrawal of Subjects* 
☐ 
N/A:  This study is not enrolling subjects.  This section does not apply. 
 
22.1 Describe anticipated circumstances under which subjects may be withdrawn 
from the research without their consent. 
Response:  If they have adverse events that could be possibly related to Melatonin 
such that the study team think their continued participation is not advisable. If 
participants are noncompliant with the research procedures, there is the possibility 
they will be withdrawn from the research.  
For those subjects that have not had a previous tests, once enrolled if the subject is 
found to be COVID-19 negative by EUA rapid antigen testing, the subject will be 
withdrawn from the study.  
 
22.2 Describe any procedures for orderly termination.   


 
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NOTE:  Examples may include return of study drug, exit interview with clinician.  
Include whether additional follow up is recommended for safety reasons for 
physical or emotional health. 
Response: An end of study visit will be conducted over the phone and a courier 
will be sent to pick up study materials and samples.  
 
22.3 Describe procedures that will be followed when subjects withdraw from the 
research, including retention of already collected data, and partial 
withdrawal from procedures with continued data collection, as applicable. 
Response:  Subjects who withdraw from taking the study drug will be encouraged 
to stay in the study.  If they choose not to, a telephonic end of study visit and 
courier collection of samples and study materials will be done. Already collected 
data and samples will not be removed from the study database. 
 
23.0 
Risks to Subjects* 
23.1 List the reasonably foreseeable risks, discomforts, hazards, or 
inconveniences to the subjects related to their participation in the research. 
Consider physical, psychological, social, legal, and economic risks.  Include 
a description of the probability, magnitude, duration, and reversibility of the 
risks.  
NOTE:  Breach of confidentiality is always a risk for identifiable subject data. 
Response:  
Nasopharyngeal swabs are associated with discomfort that is usually 
short-lived.   
 
Potential risks associated with the use of planned doses of melatonin include 
dizziness, headache, vivid dreams, nausea and sleepiness, that are anticipated to be 
of mild severity.  
Breach of confidentiality is an associated risk of this research. 
 
23.2 Describe procedures performed to lessen the probability or magnitude of 
risks, including procedures being performed to monitor subjects for safety. 
Response: The frequent telephonic follow-up and the availability of the study 
team to the participants in case adverse effects arise.  
Please see section 20.1 for procedures performed to lessen the risk of breach of 
confidentiality.  
 


 
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23.3 If applicable, indicate which procedures may have risks to the subjects that 
are currently unforeseeable. 
Response: Melatonin has never been studied in COVID patients, therefore there 
are unforeseeable risks.  
 
23.4 If applicable, indicate which research procedures may have risks to an 
embryo or fetus should the subject be or become pregnant. 
Response: Melatonin has not been studied in pregnancy.  
 
23.5 If applicable, describe risks to others who are not subjects. 
Response: NA 
 
24.0 
Potential Benefits to Subjects* 
24.1 Describe the potential benefits that individual subjects may experience by 
taking part in the research.  Include the probability, magnitude, and 
duration of the potential benefits.  Indicate if there is no direct benefit.   
NOTE:  Compensation cannot be stated as a benefit. 
Response:  
The candidate therapeutic(s) being evaluated may or may not improve clinical 
outcome of an individual adult subject with COVID-19 who participates in this 
trial. However, there is potential benefit to society from their participation in this 
study resulting from insights gained about the therapeutic agents under study as 
well as the natural history of the disease. While there may not be benefits for an 
individual subject, there may be benefits to society if a safe, efficacious 
therapeutic agent can be identified during this global COVID-19 outbreak.   
The overall risk of using Melatonin in COVID is likely to be low and the potential 
benefit is high.  This favorable risk-benefit ratio supports the conduct of this pilot 
study, and if the results of this pilot study are consistent with our expectations, a 
larger definitive trial. 
 
25.0 
Compensation for Research-Related Injury 
☐ 
N/A:  The research procedures for this study do not present risk of 
research related injury (e.g. survey studies, records review studies).  This 
section does not apply.   
25.1 
If the research procedures carry a risk of research related injury, 
describe the available compensation to subjects in the event that such 
injury should occur.   


 
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Response: There is no available compensation to subjects for research related 
injury. 
 
25.2 
Provide a copy of contract language, if any, relevant to compensation for 
research related injury. 
NOTE:  If the contract is not yet approved at the time of this submission, submit the 
current version here.  If the contract is later approved with different language 
regarding research related injury, you must modify your response here and 
submit an amendment to the IRB for review and approval. 
Response: There will be no compensation for research related injuries. 
 
26.0 
Economic Burden to Subjects 
26.1 
Describe any costs that subjects may be responsible for because of 
participation in the research.   
NOTE:  Some examples include transportation or parking. 
Response: None   
 
☐ 
N/A:  This study is not enrolling subjects, or is limited to records review 
procedures only.  This section does not apply. 
27.0 
Compensation for Participation 
27.1 
Describe the amount and timing of any compensation to subjects, 
including monetary, course credit, or gift card compensation. 
Response: Subjects will receive a one time payment of $50 for participation on 
completion of the study. 
 
☐ 
N/A:  This study is not enrolling subjects, or is limited to records 
review procedures only.  This section does not apply. 
☒ 
N/A:  There is no compensation for participation.  This section 
does not apply. 
28.0 
Consent Process 
28.1 Indicate whether you will be obtaining consent.   
NOTE:  This does not refer to consent documentation, but rather whether you will 
be obtaining permission from subjects to participate in a research study.   
Consent documentation is addressed in Section 27.0. 
☒ 
Yes 
(If yes, Provide responses to each question in this Section) 
☐ 
No 
(If no, Skip to Section 27.0) 
 


 
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28.2 Describe where the consent process will take place.  Include steps to 
maximize subjects’ privacy. 
Response:  
The consent process could take place at the ED or physician’s office, or at a 
COVID research clinic location on Maple road in Amherst under development.  
The person obtaining the consent will do so from a private room to ensure their 
conversation is not overheard.  
28.3 Describe how you will ensure that subjects are provided with a sufficient 
period of time to consider taking part in the research study.   
NOTE:  It is always a requirement that a prospective subject is given sufficient 
time to have their questions answered and consider their participation.  See “SOP: 
Informed Consent Process for Research (HRP-090)” Sections 5.5 and 5.6. 
Response: At the time of the enrollment interview, the consent will be reviewed 
and discussed with the subject and all pertinent questions answered.  Following 
the interview process, the subject will be offered additional time to decide if they 
want to participate. 
28.4 Describe any process to ensure ongoing consent, defined as a subject’s 
willingness to continue participation for the duration of the research study.   
Response:  
The subject will be informed as part of the consent process that they can withdraw 
from the study at any time.  
28.5 Indicate whether you will be following “SOP: Informed Consent Process for 
Research (HRP-090).” Pay particular attention to Sections 5.4-5.9. If not, 
or if there are any exceptions or additional details to what is covered in the 
SOP, describe: 
• 
The role of the individuals listed in the application who are involved in 
the consent process 
• 
The time that will be devoted to the consent discussion 
• 
Steps that will be taken to minimize the possibility of coercion or 
undue influence 
• 
Steps that will be taken to ensure the subjects’ understanding 
Response:  
 
☒ 
We have reviewed and will be following “SOP: Informed Consent Process 
for Research (HRP-090).” 
 
Non-English Speaking Subjects  
☐ 
N/A:  This study will not enroll Non-English speaking subjects.   
(Skip to Section 26.8) 


 
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28.6 Indicate which language(s) other than English are likely to be 
spoken/understood by your prospective study population or their legally 
authorized representatives. 
 
NOTE: The response to this Section should correspond with your response to 
Section 6.4 of this protocol. 
Response:  NA 
 
28.7 If subjects who do not speak English will be enrolled, describe the process 
to ensure that the oral and written information provided to those subjects 
will be in that language, how you will ensure that subjects are provided with 
a sufficient period of time to consider taking part in the research study, and 
any process to ensure ongoing consent. Indicate the language that will be 
used by those obtaining consent.  
NOTE:  Guidance is provided on “SOP:  Informed Consent Process for Research 
(HRP-090).” 
Response: NA 
 
 
Cognitively Impaired Adults 
☒ 
N/A:  This study will not enroll cognitively impaired adults.   
(Skip to Section 26.9) 
28.8   Describe the process to determine whether an individual is capable of 
consent.  
Response:  
 
 
Adults Unable to Consent 
☒ 
N/A:  This study will not enroll adults unable to consent.  
(Skip to Section 26.13) 
When a person is not capable of consent due to cognitive impairment, a legally 
authorized representative should be used to provide consent (Sections 26.9 and 
26.10) and, where possible, assent of the individual should also be solicited 
(Sections 26.11 and 26.12). 
28.9  Describe how you will identify a Legally Authorized Representative (LAR).  
Indicate that you have reviewed the “SOP: Legally Authorized 
Representatives, Children, and Guardians (HRP-013)” for research in New 
York State.  


 
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NOTE:  Examples of acceptable response includes: verifying the electronic 
medical record to determine if an LAR is recorded. 
Response:  
 
☐ 
We have reviewed and will be following “SOP: Legally Authorized 
Representatives, Children, and Guardians (HRP-013).”  
28.10 For research conducted outside of New York State, provide information 
that describes which individuals are authorized under applicable law to 
consent on behalf of a prospective subject to their participation in the 
research. One method of obtaining this information is to have a legal 
counsel or authority review your protocol along with the definition of 
“legally authorized representative” in “SOP: Legally Authorized 
Representatives, Children, and Guardians (HRP-013).” 
Response: NA 
 
28.11 Describe the process for assent of the adults: 
• 
Indicate whether assent will be obtained from all, some, or none of the 
subjects.  If some, indicate which adults will be required to assent 
and which will not. 
Response:  
 
• 
If assent will not be obtained from some or all subjects, provide an 
explanation of why not. 
Response:  
 
28.12 Describe whether assent of the adult subjects will be documented and the 
process to document assent.   
NOTE:  The IRB allows the person obtaining assent to document assent on the 
consent document using the “Template Consent Document (HRP-502)” Signature 
Block for Assent of Adults who are Legally Unable to Consent. 
Response:  
 
 
Subjects who are not yet Adults (Infants, Children, and Teenagers) 
☒ 
N/A:  This study will not enroll subjects who are not yet adults.   
(Skip to Section 27.0) 


 
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28.13 Describe the criteria that will be used to determine whether a prospective 
subject has not attained the legal age for consent to treatments or 
procedures involved in the research under the applicable law of the 
jurisdiction in which the research will be conducted (e.g., individuals under 
the age of 18 years).  For research conducted in NYS, review “SOP: 
Legally Authorized Representatives, Children, and Guardians (HRP-013)” 
to be aware of which individuals in the state meet the definition of 
“children.”  
NOTE:  Examples of acceptable responses include: verification via electronic 
medical record, driver’s license or state-issued ID, screening questionnaire. 
Response:  
 
28.14For research conducted outside of New York State, provide information 
that describes which persons have not attained the legal age for consent to 
treatments or procedures involved the research, under the applicable law of 
the jurisdiction in which research will be conducted.  One method of 
obtaining this information is to have a legal counsel or authority review 
your protocol along the definition of “children” in “SOP: Legally 
Authorized Representatives, Children, and Guardians (HRP-013).” 
Response:  
 
28.15 Describe whether parental permission will be obtained from: 
Response:  
☐  One parent even if the other parent is alive, known, competent, reasonably 
available, and shares legal responsibility for the care and custody of the 
child. 
☐ 
Both parents unless one parent is deceased, unknown, incompetent, or not 
reasonably available, or when only one parent has legal responsibility for 
the care and custody of the child. 
☐ 
Parent permission will not be obtained.  A waiver of parent permission is 
being requested. 
NOTE:  The requirement for parent permission is a protocol-specific determination 
made by the IRB based on the risk level of the research.  For guidance, review the 
“CHECKLIST: Children (HRP-416).”  
28.16Describe whether permission will be obtained from individuals other than 
parents, and if so, who will be allowed to provide permission.  Describe 
your procedure for determining an individual’s authority to consent to the 
child’s general medical care. 
Response:  


 
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28.17 Indicate whether assent will be obtained from all, some, or none of the 
children.  If assent will be obtained from some children, indicate which 
children will be required to assent. 
Response:  
 
28.18 When assent of children is obtained, describe how it will be documented. 
Response:  
 
29.0 
Waiver or Alteration of Consent Process 
Consent will not be obtained, required information will not be disclosed, or the 
research involves deception. 
☒ 
N/A:  A waiver or alteration of consent is not being requested. 
29.1 If the research involves a waiver or alteration of the consent process, please 
review the “CHECKLIST: Waiver or Alteration of Consent Process (HRP-
410)” to ensure that you have provided sufficient information for the IRB to 
make the determination that a waiver or alteration can be granted.   
NOTE:  For records review studies, the first set of criteria on the “CHECKLIST: 
Waiver or Alteration of Consent Process (HRP-410)” applies.  
Response:  
 
29.2 If the research involves a waiver of the consent process for planned 
emergency research, please review the “CHECKLIST: Waiver of Consent 
for Emergency Research (HRP-419)” to ensure you have provided sufficient 
information for the IRB to make these determinations.  Provide any 
additional information necessary here: 
Response:  
 
30.0 
Process to Document Consent 
☐ 
N/A:  A Waiver of Consent is being requested.   
(Skip to Section 29.0) 
30.1 Indicate whether you will be following “SOP: Written Documentation of 
Consent (HRP-091).” If not or if there are any exceptions, describe whether 
and how consent of the subject will be obtained including whether or not it 
will be documented in writing.   
NOTE:  If your research presents no more than minimal risk of harm to subjects 
and involves no procedures for which written documentation of consent is normally 
required outside of the research context, the IRB will generally waive the 


 
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requirement to obtain written documentation of consent.  This is sometimes 
referred to as ‘verbal consent.’  Review “CHECKLIST: Waiver of Written 
Documentation of Consent (HRP-411)” to ensure that you have provided sufficient 
information.  
If you will document consent in writing, attach a consent document with your 
submission.  You may use “TEMPLATE CONSENT DOCUMENT (HRP-
502)”.  If you will obtain consent, but not document consent in writing, attach the 
script of the information to be provided orally or in writing (i.e. consent script or 
Information Sheet).   
 
☒ 
We will be following “SOP:  Written Documentation of Consent” 
(HRP-091). 
31.0 
Multi-Site Research (Multisite/Multicenter Only)* 
☒ 
N/A:  This study is not an investigator-initiated multi-site study.  This 
section does not apply. 
 
31.1 
Indicate the total number of subjects that will be enrolled or records that 
will be reviewed across all sites. 
Response:  
 
31.2 If this is a multi-site study where you are the lead investigator, describe the 
processes to ensure communication among sites, such as the following. See 
“WORKSHEET: Communication and Responsibilities (HRP-830).”: 
• 
All sites have the most current version of the IRB documents, including 
the protocol, consent document, and HIPAA authorization. 
• 
All required approvals have been obtained at each site (including 
approval by the site’s IRB of record). 
• 
All modifications have been communicated to sites, and approved 
(including approval by the site’s IRB of record) before the 
modification is implemented. 
• 
All engaged participating sites will safeguard data as required by 
local information security policies. 
• 
All local site investigators conduct the study appropriately in 
accordance with applicable federal regulations and local laws. 
• 
All non-compliance with the study protocol or applicable requirements 
will be reported in accordance with local policy. 
Response:  
 
31.3 Describe the method for communicating to engaged participating sites (see 
“WORKSHEET: Communication and Responsibilities (HRP-830)”): 


 
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• 
Problems (inclusive of reportable events) 
• 
Interim results 
• 
Study closure 
Response:  
 
31.4 
If this is a multicenter study where you are a participating 
site/investigator, describe the local procedures for maintenance of 
confidentiality. (See “WORKSHEET: Communication and 
Responsibilities (HRP-830).”) 
• 
Where and how data or specimens will be stored locally? 
• 
How long the data or specimens will be stored locally? 
• 
Who will have access to the data or specimens locally? 
• 
Who is responsible for receipt or transmission of the data or 
specimens locally? 
• 
How data and specimens will be transported locally? 
Response:  
 
31.5 
If this is a multicenter study and subjects will be recruited by methods not 
under the control of the local site (e.g., call centers, national 
advertisements) describe those methods.  Local recruitment methods are 
described elsewhere in the protocol. 
• 
Describe when, where, and how potential subjects will be 
recruited. 
• 
Describe the methods that will be used to identify potential 
subjects. 
• 
Describe materials that will be used to recruit subjects. (Attach 
copies of these documents with the application. For 
advertisements, attach the final copy of printed advertisements. 
When advertisements are taped for broadcast, attach the final 
audio/video tape. You may submit the wording of the 
advertisement prior to taping to preclude re-taping because of 
inappropriate wording, provided the IRB reviews the final 
audio/video tape.) 
Response:  
 
32.0 
Banking Data or Specimens for Future Use* 
☒ 
N/A:  This study is not banking data or specimens for future use or 
research outside the scope of the present protocol.  This section does not 
apply. 


 
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32.1 If data or specimens will be banked (stored) for future use, that is, use or 
research outside of the scope of the present protocol, describe where the 
data/specimens will be stored, how long they will be stored, how the 
data/specimens will be accessed, and who will have access to the 
data/specimens.  
NOTE:  Your response here must be consistent with your response at the “What 
happens if I say yes, I want to be in this research?” Section of the Template 
Consent Document (HRP-502). 
Response:   
 
32.2 List the data to be stored or associated with each specimen. 
Response:  
 
32.3 Describe the procedures to release banked data or specimens for future 
uses, including: the process to request a release, approvals required for 
release, who can obtain data or specimens, and the data to be provided with 
specimens. 
Response: