<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04474483</url>
  </required_header>
  <id_info>
    <org_study_id>UBMELCOVID19</org_study_id>
    <nct_id>NCT04474483</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Melatonin in Outpatients Infected With COVID-19</brief_title>
  <acronym>COVID-19</acronym>
  <official_title>A Pilot Placebo-controlled Randomized Double-blind Trial of Melatonin in Outpatients With COVID-19 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>State University of New York at Buffalo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>State University of New York at Buffalo</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a pilot randomized, double-blind, placebo-controlled clinical trial to evaluate&#xD;
      the safety and efficacy of melatonin in adult outpatients suspected to be afflicted with&#xD;
      COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a pilot randomized, double-blind, placebo-controlled clinical trial to evaluate&#xD;
      the safety and efficacy of melatonin in outpatient adult patients suspected to be afflicted&#xD;
      with COVID-19. Participants will be enrolled as outpatients within 72 hrs of onset of&#xD;
      COVID-19 symptoms. The study will evaluate the safety of the intervention through 28 days of&#xD;
      follow-up as compared to the control arm as assessed by cumulative incidence of serious&#xD;
      adverse events (SAEs), cumulative incidence of Grade 3 and 4 adverse events (AEs), and/or&#xD;
      discontinuation or temporary suspension of the investigational medication (for any reason).&#xD;
      Additionally, the study will aim to evaluate the clinical efficacy of melatonin as compared&#xD;
      to placebo as assessed by hospitalization, COVID-19 related symptoms and mortality. The&#xD;
      ultimate goal is to determine in an adequately powered study if the anti-inflammatory and&#xD;
      antioxidant actions of Melatonin can reduce the severity and prevent progression of COVID-19&#xD;
      when started in mild disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    difficult recruitment and complete first visit in person during thne hight of tne pandemic and&#xD;
    later not enough subjects&#xD;
  </why_stopped>
  <start_date type="Actual">November 6, 2020</start_date>
  <completion_date type="Actual">July 22, 2022</completion_date>
  <primary_completion_date type="Actual">July 22, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>placebo-controlled randomized double-blind pilot trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cumulative Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>28 days</time_frame>
    <description>Evaluate the incidence of serious adverse effects and discontinuation secondary to toxicity through 28 days of follow-up as compared to the control arm as assessed by: Cumulative incidence of serious adverse events (SAEs), Cumulative incidence of Grade 3 and 4 adverse events (AEs), Discontinuation or temporary suspension of the investigational medication (for any reason).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hospitalization</measure>
    <time_frame>28 days</time_frame>
    <description>Incidence of COVID-19 related hospitalization at 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>COVID-19 related symptoms</measure>
    <time_frame>28 days</time_frame>
    <description>COVID-19 related symptoms (Fever, chills, cough, nasal symptoms, body aches/muscle aches, headache, loss of smell, loss of taste, nausea, vomiting, diarrhea, fatigue, dizziness) that are self-reported and on interview.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of resolution of COVID-19 related symptoms</measure>
    <time_frame>28 days</time_frame>
    <description>Change from baseline (day 1) as assessed to days 3, 7, 14, and 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>28 days</time_frame>
    <description>28-day mortality</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Melatonin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin</intervention_name>
    <description>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.</description>
    <arm_group_label>Melatonin</arm_group_label>
    <other_name>5-methoxy-N-acetyl tryptamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo (Methylcellulose) capsule</intervention_name>
    <description>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.</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Methylcellulose</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or non-pregnant female adult ≥18 years of age at time of enrollment.&#xD;
&#xD;
          -  Women of childbearing potential must agree to use at least one primary form of&#xD;
             contraception for the duration of the study.&#xD;
&#xD;
          -  Subject provides written informed consent prior to initiation of any study procedures.&#xD;
&#xD;
          -  Understands and agrees to comply with planned study procedures.&#xD;
&#xD;
          -  Agrees to the collection and storage of saliva samples per protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe chronic liver disease&#xD;
&#xD;
          -  Severe chronic kidney disease or requiring dialysis&#xD;
&#xD;
          -  Pregnancy or breast feeding.&#xD;
&#xD;
          -  Allergy to the study medication&#xD;
&#xD;
          -  Currently taking melatonin&#xD;
&#xD;
          -  Currently taking high dose (&gt;500 mg/day) Vitamin C&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Margarita L Dubocovich, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University at Buffalo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University at Buffalo</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html</url>
    <description>CDC. 2020. 'Coronavirus Disease 2019 (COVID-19)'.</description>
  </link>
  <reference>
    <citation>Aliasgharzadeh A, Farhood B, Amini P, Saffar H, Motevaseli E, Rezapoor S, Nouruzi F, Shabeeb DH, Eleojo Musa A, Mohseni M, Moradi H, Najafi M. Melatonin Attenuates Upregulation of Duox1 and Duox2 and Protects against Lung Injury following Chest Irradiation in Rats. Cell J. 2019 Oct;21(3):236-242. doi: 10.22074/cellj.2019.6207. Epub 2019 Jun 15.</citation>
    <PMID>31210428</PMID>
  </reference>
  <reference>
    <citation>Andersen LP, Gogenur I, Rosenberg J, Reiter RJ. The Safety of Melatonin in Humans. Clin Drug Investig. 2016 Mar;36(3):169-75. doi: 10.1007/s40261-015-0368-5.</citation>
    <PMID>26692007</PMID>
  </reference>
  <reference>
    <citation>Bazyar H, Gholinezhad H, Moradi L, Salehi P, Abadi F, Ravanbakhsh M, Zare Javid A. The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: a double-blind, placebo-controlled trial. Inflammopharmacology. 2019 Feb;27(1):67-76. doi: 10.1007/s10787-018-0539-0. Epub 2018 Oct 16.</citation>
    <PMID>30328031</PMID>
  </reference>
  <reference>
    <citation>Chen CF, Wang D, Reiter RJ, Yeh DY. Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats. J Pineal Res. 2011 Jan;50(1):46-53. doi: 10.1111/j.1600-079X.2010.00808.x. Epub 2010 Oct 22.</citation>
    <PMID>20964706</PMID>
  </reference>
  <reference>
    <citation>Cheung CY, Poon LL, Ng IH, Luk W, Sia SF, Wu MH, Chan KH, Yuen KY, Gordon S, Guan Y, Peiris JS. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J Virol. 2005 Jun;79(12):7819-26. doi: 10.1128/JVI.79.12.7819-7826.2005.</citation>
    <PMID>15919935</PMID>
  </reference>
  <reference>
    <citation>Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:</citation>
    <PMID>31986264</PMID>
  </reference>
  <reference>
    <citation>Kim JY, Lee YD, Kim BJ, Kim SP, Kim DH, Jo KJ, Lee SK, Lee KH, Baik HW. Melatonin improves inflammatory cytokine profiles in lung inflammation associated with sleep deprivation. Mol Med Rep. 2012 May;5(5):1281-4. doi: 10.3892/mmr.2012.814. Epub 2012 Feb 29.</citation>
    <PMID>22377793</PMID>
  </reference>
  <reference>
    <citation>Law HK, Cheung CY, Ng HY, Sia SF, Chan YO, Luk W, Nicholls JM, Peiris JS, Lau YL. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood. 2005 Oct 1;106(7):2366-74. doi: 10.1182/blood-2004-10-4166. Epub 2005 Apr 28.</citation>
    <PMID>15860669</PMID>
  </reference>
  <reference>
    <citation>Pedreira PR, Garcia-Prieto E, Parra D, Astudillo A, Diaz E, Taboada F, Albaiceta GM. Effects of melatonin in an experimental model of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L820-7. doi: 10.1152/ajplung.90211.2008. Epub 2008 Sep 19.</citation>
    <PMID>18805959</PMID>
  </reference>
  <reference>
    <citation>Peng Z, Zhang W, Qiao J, He B. Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1beta in rats with COPD. Int Immunopharmacol. 2018 Sep;62:23-28. doi: 10.1016/j.intimp.2018.06.033. Epub 2018 Jun 30.</citation>
    <PMID>29990691</PMID>
  </reference>
  <reference>
    <citation>Sanchez-Lopez AL, Ortiz GG, Pacheco-Moises FP, Mireles-Ramirez MA, Bitzer-Quintero OK, Delgado-Lara DLC, Ramirez-Jirano LJ, Velazquez-Brizuela IE. Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis. Arch Med Res. 2018 Aug;49(6):391-398. doi: 10.1016/j.arcmed.2018.12.004. Epub 2018 Dec 27.</citation>
    <PMID>30595364</PMID>
  </reference>
  <reference>
    <citation>Shang Y, Xu SP, Wu Y, Jiang YX, Wu ZY, Yuan SY, Yao SL. Melatonin reduces acute lung injury in endotoxemic rats. Chin Med J (Engl). 2009 Jun 20;122(12):1388-93.</citation>
    <PMID>19567158</PMID>
  </reference>
  <reference>
    <citation>Shin IS, Park JW, Shin NR, Jeon CM, Kwon OK, Kim JS, Kim JC, Oh SR, Ahn KS. Melatonin reduces airway inflammation in ovalbumin-induced asthma. Immunobiology. 2014 Dec;219(12):901-8. doi: 10.1016/j.imbio.2014.08.004. Epub 2014 Aug 10.</citation>
    <PMID>25161126</PMID>
  </reference>
  <reference>
    <citation>Wang S, Zhao Z, Feng X, Cheng Z, Xiong Z, Wang T, Lin J, Zhang M, Hu J, Fan Y, Reiter RJ, Wang H, Sun D. Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition. J Cell Mol Med. 2018 Oct;22(10):5132-5144. doi: 10.1111/jcmm.13802. Epub 2018 Jul 31.</citation>
    <PMID>30063115</PMID>
  </reference>
  <reference>
    <citation>Wu GC, Peng CK, Liao WI, Pao HP, Huang KL, Chu SJ. Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production. Respir Res. 2020 Mar 6;21(1):65. doi: 10.1186/s12931-020-1325-2.</citation>
    <PMID>32143642</PMID>
  </reference>
  <reference>
    <citation>Wu WS, Chou MT, Chao CM, Chang CK, Lin MT, Chang CP. Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats. Acta Pharmacol Sin. 2012 Jun;33(6):775-82. doi: 10.1038/aps.2012.29. Epub 2012 May 21.</citation>
    <PMID>22609835</PMID>
  </reference>
  <reference>
    <citation>Zhao X, Sun J, Su W, Shan H, Zhang B, Wang Y, Shabanova A, Shan H, Liang H. Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway. Int J Mol Sci. 2018 Apr 9;19(4):1118. doi: 10.3390/ijms19041118.</citation>
    <PMID>29642520</PMID>
  </reference>
  <reference>
    <citation>Zhang R, Wang X, Ni L, Di X, Ma B, Niu S, Liu C, Reiter RJ. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020 Jun 1;250:117583. doi: 10.1016/j.lfs.2020.117583. Epub 2020 Mar 23.</citation>
    <PMID>32217117</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>April 18, 2023</last_update_submitted>
  <last_update_submitted_qc>April 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>State University of New York at Buffalo</investigator_affiliation>
    <investigator_full_name>Margarita L. Dubocovich, PhD</investigator_full_name>
    <investigator_title>SUNY Distinguished Professor Dept of Pharmacology and Toxicology</investigator_title>
  </responsible_party>
  <keyword>Melatonin</keyword>
  <keyword>COVID-19</keyword>
  <keyword>SARS-CoV-2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04474483
org study id: UBMELCOVID19
nct id: NCT04474483
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study is a pilot randomized, double-blind, placebo-controlled clinical trial to evaluate
      the safety and efficacy of melatonin in adult outpatients suspected to be afflicted with
      COVID-19.
This study is a pilot randomized, double-blind, placebo-controlled clinical trial to evaluate
      the safety and efficacy of melatonin in outpatient adult patients suspected to be afflicted
      with COVID-19. Participants will be enrolled as outpatients within 72 hrs of onset of
      COVID-19 symptoms. The study will evaluate the safety of the intervention through 28 days of
      follow-up as compared to the control arm as assessed by cumulative incidence of serious
      adverse events (SAEs), cumulative incidence of Grade 3 and 4 adverse events (AEs), and/or
      discontinuation or temporary suspension of the investigational medication (for any reason).
      Additionally, the study will aim to evaluate the clinical efficacy of melatonin as compared
      to placebo as assessed by hospitalization, COVID-19 related symptoms and mortality. The
      ultimate goal is to determine in an adequately powered study if the anti-inflammatory and
      antioxidant actions of Melatonin can reduce the severity and prevent progression of COVID-19
      when started in mild disease.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: placebo-controlled randomized double-blind pilot trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Cumulative Incidence of Treatment-Emergent Adverse Events
time frame: 28 days
description: Evaluate the incidence of serious adverse effects and discontinuation secondary to toxicity through 28 days of follow-up as compared to the control arm as assessed by: Cumulative incidence of serious adverse events (SAEs), Cumulative incidence of Grade 3 and 4 adverse events (AEs), Discontinuation or temporary suspension of the investigational medication (for any reason).
measure: Hospitalization
time frame: 28 days
description: Incidence of COVID-19 related hospitalization at 28 days
measure: COVID-19 related symptoms
time frame: 28 days
description: COVID-19 related symptoms (Fever, chills, cough, nasal symptoms, body aches/muscle aches, headache, loss of smell, loss of taste, nausea, vomiting, diarrhea, fatigue, dizziness) that are self-reported and on interview.
measure: Rate of resolution of COVID-19 related symptoms
time frame: 28 days
description: Change from baseline (day 1) as assessed to days 3, 7, 14, and 28
measure: Mortality
time frame: 28 days
description: 28-day mortality
arm group label: Control
arm group type: Placebo Comparator
description: 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 group label: Melatonin
arm group type: Experimental
description: 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 type: Drug
intervention name: Melatonin
description: 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.
arm group label: Melatonin
other name: 5-methoxy-N-acetyl tryptamine
intervention type: Other
intervention name: Placebo (Methylcellulose) capsule
description: 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 group label: Control
other name: Methylcellulose
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Margarita L Dubocovich, Ph.D.
role: Principal Investigator
affiliation: University at Buffalo
facility: 
country: United States
url: https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html
description: CDC. 2020. 'Coronavirus Disease 2019 (COVID-19)'.
citation: Aliasgharzadeh A, Farhood B, Amini P, Saffar H, Motevaseli E, Rezapoor S, Nouruzi F, Shabeeb DH, Eleojo Musa A, Mohseni M, Moradi H, Najafi M. Melatonin Attenuates Upregulation of Duox1 and Duox2 and Protects against Lung Injury following Chest Irradiation in Rats. Cell J. 2019 Oct;21(3):236-242. doi: 10.22074/cellj.2019.6207. Epub 2019 Jun 15.
PMID: 31210428
citation: Andersen LP, Gogenur I, Rosenberg J, Reiter RJ. The Safety of Melatonin in Humans. Clin Drug Investig. 2016 Mar;36(3):169-75. doi: 10.1007/s40261-015-0368-5.
PMID: 26692007
citation: Bazyar H, Gholinezhad H, Moradi L, Salehi P, Abadi F, Ravanbakhsh M, Zare Javid A. The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: a double-blind, placebo-controlled trial. Inflammopharmacology. 2019 Feb;27(1):67-76. doi: 10.1007/s10787-018-0539-0. Epub 2018 Oct 16.
PMID: 30328031
citation: Chen CF, Wang D, Reiter RJ, Yeh DY. Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats. J Pineal Res. 2011 Jan;50(1):46-53. doi: 10.1111/j.1600-079X.2010.00808.x. Epub 2010 Oct 22.
PMID: 20964706
citation: Cheung CY, Poon LL, Ng IH, Luk W, Sia SF, Wu MH, Chan KH, Yuen KY, Gordon S, Guan Y, Peiris JS. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J Virol. 2005 Jun;79(12):7819-26. doi: 10.1128/JVI.79.12.7819-7826.2005.
PMID: 15919935
citation: Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:
PMID: 31986264
citation: Kim JY, Lee YD, Kim BJ, Kim SP, Kim DH, Jo KJ, Lee SK, Lee KH, Baik HW. Melatonin improves inflammatory cytokine profiles in lung inflammation associated with sleep deprivation. Mol Med Rep. 2012 May;5(5):1281-4. doi: 10.3892/mmr.2012.814. Epub 2012 Feb 29.
PMID: 22377793
citation: Law HK, Cheung CY, Ng HY, Sia SF, Chan YO, Luk W, Nicholls JM, Peiris JS, Lau YL. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood. 2005 Oct 1;106(7):2366-74. doi: 10.1182/blood-2004-10-4166. Epub 2005 Apr 28.
PMID: 15860669
citation: Pedreira PR, Garcia-Prieto E, Parra D, Astudillo A, Diaz E, Taboada F, Albaiceta GM. Effects of melatonin in an experimental model of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L820-7. doi: 10.1152/ajplung.90211.2008. Epub 2008 Sep 19.
PMID: 18805959
citation: Peng Z, Zhang W, Qiao J, He B. Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1beta in rats with COPD. Int Immunopharmacol. 2018 Sep;62:23-28. doi: 10.1016/j.intimp.2018.06.033. Epub 2018 Jun 30.
PMID: 29990691
citation: Sanchez-Lopez AL, Ortiz GG, Pacheco-Moises FP, Mireles-Ramirez MA, Bitzer-Quintero OK, Delgado-Lara DLC, Ramirez-Jirano LJ, Velazquez-Brizuela IE. Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis. Arch Med Res. 2018 Aug;49(6):391-398. doi: 10.1016/j.arcmed.2018.12.004. Epub 2018 Dec 27.
PMID: 30595364
citation: Shang Y, Xu SP, Wu Y, Jiang YX, Wu ZY, Yuan SY, Yao SL. Melatonin reduces acute lung injury in endotoxemic rats. Chin Med J (Engl). 2009 Jun 20;122(12):1388-93.
PMID: 19567158
citation: Shin IS, Park JW, Shin NR, Jeon CM, Kwon OK, Kim JS, Kim JC, Oh SR, Ahn KS. Melatonin reduces airway inflammation in ovalbumin-induced asthma. Immunobiology. 2014 Dec;219(12):901-8. doi: 10.1016/j.imbio.2014.08.004. Epub 2014 Aug 10.
PMID: 25161126
citation: Wang S, Zhao Z, Feng X, Cheng Z, Xiong Z, Wang T, Lin J, Zhang M, Hu J, Fan Y, Reiter RJ, Wang H, Sun D. Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition. J Cell Mol Med. 2018 Oct;22(10):5132-5144. doi: 10.1111/jcmm.13802. Epub 2018 Jul 31.
PMID: 30063115
citation: Wu GC, Peng CK, Liao WI, Pao HP, Huang KL, Chu SJ. Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production. Respir Res. 2020 Mar 6;21(1):65. doi: 10.1186/s12931-020-1325-2.
PMID: 32143642
citation: Wu WS, Chou MT, Chao CM, Chang CK, Lin MT, Chang CP. Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats. Acta Pharmacol Sin. 2012 Jun;33(6):775-82. doi: 10.1038/aps.2012.29. Epub 2012 May 21.
PMID: 22609835
citation: Zhao X, Sun J, Su W, Shan H, Zhang B, Wang Y, Shabanova A, Shan H, Liang H. Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway. Int J Mol Sci. 2018 Apr 9;19(4):1118. doi: 10.3390/ijms19041118.
PMID: 29642520
citation: Zhang R, Wang X, Ni L, Di X, Ma B, Niu S, Liu C, Reiter RJ. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020 Jun 1;250:117583. doi: 10.1016/j.lfs.2020.117583. Epub 2020 Mar 23.
PMID: 32217117
responsible party type: Principal Investigator
investigator affiliation: State University of New York at Buffalo
investigator full name: Margarita L. Dubocovich, PhD
investigator title: SUNY Distinguished Professor Dept of Pharmacology and Toxicology
mesh term: COVID-19
mesh term: Melatonin