<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/NCT03764020</url>
  </required_header>
  <id_info>
    <org_study_id>TUMS</org_study_id>
    <nct_id>NCT03764020</nct_id>
  </id_info>
  <brief_title>Trial of Oral Melatonin in Elevated Blood Pressure</brief_title>
  <acronym>MRCTEBP</acronym>
  <official_title>A Triple Blinded Randomized Controlled Trial of Oral Melatonin in Elevated Blood Pressure Individual (MRCTEBP)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tehran University of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tehran University of Medical Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Since, lowering blood pressure (BP) in elevated blood pressure individuals represents an&#xD;
      excellent opportunity to for primary prevention of hypertension (HTN). Therefore, it is&#xD;
      planned to use a safe treatment option - oral melatonin supplementation - associated with&#xD;
      lifestyle interventions according to the American college of cardiology/American heart&#xD;
      association (ACC/AHA) 2013 guideline in elevated blood pressure individuals to mitigate&#xD;
      systolic and diastolic BP and ultimately, to prevent the development of HTN.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Melatonin therapy can lower the systolic and diastolic BP of elevated blood pressure&#xD;
      individuals Melatonin can attenuate levels of circulatory biomarkers of Hs- CRP, Cholesterol,&#xD;
      LDL-c and triglyceride&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design: Randomized controlled trial (RCT)&#xD;
&#xD;
      Study population: Elevated blood pressure individuals who present themselves at the&#xD;
      outpatient clinics of Tehran Heart Centre(THC) , seeking blood pressure treatment and who&#xD;
      have a systolic blood pressure of 120-129 mmHg or a diastolic blood pressure of =80 mmHg.&#xD;
&#xD;
      Treatment groups: Melatonin 3 mg versus placebo&#xD;
&#xD;
      sample size: 160 per group ( 320 overall)&#xD;
&#xD;
      Treatment allocation: After completing informed consent and prior to randomization, all&#xD;
      participants undergo complete physical examination and laboratory test. Baseline levels of&#xD;
      inflammatory biomarkers and pregnancy test (for women in reproductive age) will be performed.&#xD;
      Sleep quality, actual sleep time, and sleep latency will be recorded.&#xD;
&#xD;
      Treatment plan: Three weeks melatonin 3 Mg or placebo one hour before bedtime has been&#xD;
      planned. All of the melatonin and placebo capsules will be supplied from a single hospital&#xD;
      pharmacy and free of charge to the participants. Melatonin and placebo capsules will be&#xD;
      identical. Participants will receive a three weeks supply at the assignment time. Besides,&#xD;
      all participants will receive a careful plan of adherence to a heart-healthy diet, regular&#xD;
      exercise, instruction for avoidance of tobacco use and maintenance of a healthy body mass&#xD;
      index (BMI) according to 2013ACC/ AHA guideline.&#xD;
&#xD;
      Follow up: Three weeks&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 1, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2019</primary_completion_date>
  <phase>Phase 3</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>Melatonin 3 Mg or placebo associated with life style modification according to 2013ACC/ AHA guideline has been planned in parallel fashion for three weeks of follow up. Participants allocated to each group will stay at the same interventional group for entire follow up period of three weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>Triple blinding is planned. All participants, medical providers and outcome evaluators will be blinded about treatment arms.&#xD;
The THC pharmacy will dispense the medication and perform the randomization. Melatonin capsule and placebo will be completely identical.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mean change in systolic blood pressure from baseline</measure>
    <time_frame>From enrollment to end of treatment at 3 weeks</time_frame>
    <description>Mean change in Systolic blood pressure from baseline in Millimeter Mercury, it measures average changes in systolic blood pressure. The best outcome value is &lt; and =120 millimeter mercury. Systolic blood pressure ranges between 90-250 millimeter mercury.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean change in diastolic blood pressure from baseline</measure>
    <time_frame>From enrollment to end of treatment at 3 weeks</time_frame>
    <description>Mean change in diastolic blood pressure from baseline in Millimeter Mercury, it measures average changes in systolic blood pressure. The best outcome value is &lt; 80 millimeter mercury. Diastolic blood pressure ranges between 60-140 millimeter mercury.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean change in cholesterol</measure>
    <time_frame>From enrollment to end of treatment at 3 weeks</time_frame>
    <description>Mean change in cholesterol in Milligram/deciliter from baseline, it measures average changes in cholesterol. The best outcome value is 200 milligram per deciliter. Total cholesterol less than 200 milligram per deciliter are considered desirable for adults. A reading between200-239 is considered borderline and a reading of 240 above is considered high.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean change in low density lipoprotein</measure>
    <time_frame>From enrollment to end of treatment at 3 weeks</time_frame>
    <description>Mean change in low density lipoprotein in Milligram/deciliter from baseline, it measures average changes in low density lipoprotein. The best outcome value is 100 milligram per deciliter. LDL level less than 100 milligram per deciliter is considered desirable, 100-130 borderline, 130-189 borderline high and above 190 is considered high.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean change in fasting blood sugar</measure>
    <time_frame>From enrollment to end of treatment at 3 weeks</time_frame>
    <description>Mean change in fasting blood sugar in Milligram/deciliter from baseline, it measures average changes in fasting blood sugar. Fasting blood sugar 72-99 milligram per deciliter is considered normal, 100-116 borderline and above 116 is considered high.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean change in inflammatory biomarker</measure>
    <time_frame>From enrollment to end of treatment at 3 weeks</time_frame>
    <description>Mean change in high sensitive C reactive protein (Hs-CRP) in Milligram/liter, it measures average changes in high sensitive C reactive protein (Hs-CRP). The best outcome value is &lt;= 3 milligram per liter.&#xD;
1-3 milligram per liter is considered normal and above 3 is considered high.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean change in sleep quality score from baseline</measure>
    <time_frame>From enrollment to end of treatment at 3 weeks</time_frame>
    <description>Mean change in Pittsburg sleep quality questionnaire in Likert numerical score from baseline, it measures average changes in sleep quality score. Pittsburg sleep quality questionnaire score of 5 or greater is indicative of poor sleep quality.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">320</enrollment>
  <condition>Elevated Blood Pressure</condition>
  <arm_group>
    <arm_group_label>Melatonin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention group1:&#xD;
Melatonin,capsule,3 mg, one dose one hour before bedtime, three weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intervention group2 :&#xD;
Placebo, capsule, 3 mg, one dose one hour before bedtime, for three weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule/placebo comparator</intervention_name>
    <description>3 mg placebo capsule one hour before bedtime for three weeks along with life style modification according to ACC/AHA 2013 guideline</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin/experimental</intervention_name>
    <description>Melatonin ,capsule, 3 mg, one dose one hour before bedtime, for three weeks along with life style modification according to ACC/AHA 2013 guideline.</description>
    <arm_group_label>Melatonin</arm_group_label>
    <other_name>Melatona</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals with systolic blood pressure120-129 and/or diastolic blood pressure&#xD;
             =80mmHg&#xD;
&#xD;
          -  Negative pregnancy test for women at productive age&#xD;
&#xD;
          -  Baseline melatonin and biomarkers level and complete liver function tests within&#xD;
             normal range&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous history of hypersensitivity of melatonin&#xD;
&#xD;
          -  Past history of using antihypertensive treatment&#xD;
&#xD;
          -  Past medical history of hypertension, cardiovascular diseases, (i.e. coronary artery&#xD;
             disease), and diabetes mellitus, epilepsy and other physician documented diseases&#xD;
&#xD;
          -  Use of beta-blockers, sleep aids, warfarin, flaxseed, soy and supplements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>zinat Hatmi, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tehran University of Medical Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>zinat Hatmi</last_name>
    <phone>+982164053219</phone>
    <email>hatmizn@sina.tums.ac.ir</email>
  </overall_contact>
  <reference>
    <citation>Ekmekcioglu C, Thalhammer T, Humpeler S, Mehrabi MR, Glogar HD, Holzenbein T, Markovic O, Leibetseder VJ, Strauss-Blasche G, Marktl W. The melatonin receptor subtype MT2 is present in the human cardiovascular system. J Pineal Res. 2003 Aug;35(1):40-4. doi: 10.1034/j.1600-079x.2003.00051.x.</citation>
    <PMID>12823612</PMID>
  </reference>
  <reference>
    <citation>Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR. Melatonin--a pleiotropic, orchestrating regulator molecule. Prog Neurobiol. 2011 Mar;93(3):350-84. doi: 10.1016/j.pneurobio.2010.12.004. Epub 2010 Dec 28.</citation>
    <PMID>21193011</PMID>
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  <reference>
    <citation>Jonas M, Garfinkel D, Zisapel N, Laudon M, Grossman E. Impaired nocturnal melatonin secretion in non-dipper hypertensive patients. Blood Press. 2003;12(1):19-24.</citation>
    <PMID>12699131</PMID>
  </reference>
  <reference>
    <citation>Girotti L, Lago M, Ianovsky O, Elizari MV, Dini A, Perez Lloret S, Albornoz LE, Cardinali DP. Low urinary 6-sulfatoxymelatonin levels in patients with severe congestive heart failure. Endocrine. 2003 Dec;22(3):245-8. doi: 10.1385/ENDO:22:3:245.</citation>
    <PMID>14709797</PMID>
  </reference>
  <reference>
    <citation>Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia MJ, Sanchez J, Marrero F, de Armas-Trujillo D. Decreased nocturnal melatonin levels during acute myocardial infarction. J Pineal Res. 2002 Nov;33(4):248-52. doi: 10.1034/j.1600-079x.2002.02938.x.</citation>
    <PMID>12390508</PMID>
  </reference>
  <reference>
    <citation>Dominguez-Rodriguez A, Abreu-Gonzalez P, Sanchez-Sanchez JJ, Kaski JC, Reiter RJ. Melatonin and circadian biology in human cardiovascular disease. J Pineal Res. 2010 Aug;49(1):14-22. doi: 10.1111/j.1600-079X.2010.00773.x. Epub 2010 Jun 1.</citation>
    <PMID>20536686</PMID>
  </reference>
  <reference>
    <citation>Arangino S, Cagnacci A, Angiolucci M, Vacca AM, Longu G, Volpe A, Melis GB. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol. 1999 May 1;83(9):1417-9. doi: 10.1016/s0002-9149(99)00112-5.</citation>
    <PMID>10235107</PMID>
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  <reference>
    <citation>Cagnacci A, Arangino S, Angiolucci M, Maschio E, Longu G, Melis GB. Potentially beneficial cardiovascular effects of melatonin administration in women. J Pineal Res. 1997 Jan;22(1):16-9. doi: 10.1111/j.1600-079x.1997.tb00297.x.</citation>
    <PMID>9062865</PMID>
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    <citation>Cagnacci A, Arangino S, Angiolucci M, Maschio E, Melis GB. Influences of melatonin administration on the circulation of women. Am J Physiol. 1998 Feb;274(2):R335-8. doi: 10.1152/ajpregu.1998.274.2.R335.</citation>
    <PMID>9486289</PMID>
  </reference>
  <reference>
    <citation>Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004 Feb;43(2):192-7. doi: 10.1161/01.HYP.0000113293.15186.3b. Epub 2004 Jan 19.</citation>
    <PMID>14732734</PMID>
  </reference>
  <reference>
    <citation>Cagnacci A, Cannoletta M, Renzi A, Baldassari F, Arangino S, Volpe A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005 Dec;18(12 Pt 1):1614-8. doi: 10.1016/j.amjhyper.2005.05.008.</citation>
    <PMID>16364834</PMID>
  </reference>
  <reference>
    <citation>Grossman E, Laudon M, Yalcin R, Zengil H, Peleg E, Sharabi Y, Kamari Y, Shen-Orr Z, Zisapel N. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 2006 Oct;119(10):898-902. doi: 10.1016/j.amjmed.2006.02.002.</citation>
    <PMID>17000226</PMID>
  </reference>
  <reference>
    <citation>Gubin DG, Gubin GD, Gapon LI, Weinert D. Daily Melatonin Administration Attenuates Age-Dependent Disturbances of Cardiovascular Rhythms. Curr Aging Sci. 2016;9(1):5-13. doi: 10.2174/1874609809666151130220011.</citation>
    <PMID>26632428</PMID>
  </reference>
  <reference>
    <citation>Mesri Alamdari N, Mahdavi R, Roshanravan N, Lotfi Yaghin N, Ostadrahimi AR, Faramarzi E. A double-blind, placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women. Horm Metab Res. 2015 Jun;47(7):504-8. doi: 10.1055/s-0034-1384587. Epub 2014 Aug 15.</citation>
    <PMID>25126957</PMID>
  </reference>
  <reference>
    <citation>Kozirog M, Poliwczak AR, Duchnowicz P, Koter-Michalak M, Sikora J, Broncel M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. 2011 Apr;50(3):261-6. doi: 10.1111/j.1600-079X.2010.00835.x. Epub 2010 Dec 8.</citation>
    <PMID>21138476</PMID>
  </reference>
  <reference>
    <citation>Galley HF, Lowes DA, Allen L, Cameron G, Aucott LS, Webster NR. Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis. J Pineal Res. 2014 May;56(4):427-38. doi: 10.1111/jpi.12134. Epub 2014 Apr 5.</citation>
    <PMID>24650045</PMID>
  </reference>
  <reference>
    <citation>Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol. 2000 May;49(5):423-7. doi: 10.1046/j.1365-2125.2000.00195.x.</citation>
    <PMID>10792199</PMID>
  </reference>
  <reference>
    <citation>Rechcinski T, Trzos E, Wierzbowska-Drabik K, Krzeminska-Pakula M, Kurpesa M. Melatonin for nondippers with coronary artery disease: assessment of blood pressure profile and heart rate variability. Hypertens Res. 2010 Jan;33(1):56-61. doi: 10.1038/hr.2009.174. Epub 2009 Oct 30.</citation>
    <PMID>19876062</PMID>
  </reference>
  <reference>
    <citation>Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves JW, Hill MN, Jones DH, Kurtz T, Sheps SG, Roccella EJ; Council on High Blood Pressure Research Professional and Public Education Subcommittee, American Heart Association. Recommendations for blood pressure measurement in humans: an AHA scientific statement from the Council on High Blood Pressure Research Professional and Public Education Subcommittee. J Clin Hypertens (Greenwich). 2005 Feb;7(2):102-9. doi: 10.1111/j.1524-6175.2005.04377.x. No abstract available.</citation>
    <PMID>15722655</PMID>
  </reference>
  <reference>
    <citation>Fuchs SC, Poli-de-Figueiredo CE, Figueiredo Neto JA, Scala LC, Whelton PK, Mosele F, de Mello RB, Vilela-Martin JF, Moreira LB, Chaves H, Mota Gomes M, de Sousa MR, Silva RP, Castro I, Cesarino EJ, Jardim PC, Alves JG, Steffens AA, Brandao AA, Consolim-Colombo FM, de Alencastro PR, Neto AA, Nobrega AC, Franco RS, Sobral Filho DC, Bordignon A, Nobre F, Schlatter R, Gus M, Fuchs FC, Berwanger O, Fuchs FD. Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER-Prevention Randomized Clinical Trial. J Am Heart Assoc. 2016 Dec 13;5(12):e004248. doi: 10.1161/JAHA.116.004248.</citation>
    <PMID>27965209</PMID>
  </reference>
  <reference>
    <citation>Collier SR, Landram MJ. Treatment of prehypertension: lifestyle and/or medication. Vasc Health Risk Manag. 2012;8:613-9. doi: 10.2147/VHRM.S29138. Epub 2012 Nov 15.</citation>
    <PMID>23172989</PMID>
  </reference>
  <results_reference>
    <citation>Pandi-Perumal SR, BaHammam AS, Ojike NI, Akinseye OA, Kendzerska T, Buttoo K, Dhandapany PS, Brown GM, Cardinali DP. Melatonin and Human Cardiovascular Disease. J Cardiovasc Pharmacol Ther. 2017 Mar;22(2):122-132. doi: 10.1177/1074248416660622. Epub 2016 Jul 27.</citation>
    <PMID>27450357</PMID>
  </results_reference>
  <results_reference>
    <citation>Dominguez-Rodriguez A, Abreu-Gonzalez P, Reiter RJ. Melatonin and cardiovascular disease: myth or reality? Rev Esp Cardiol (Engl Ed). 2012 Mar;65(3):215-8. doi: 10.1016/j.recesp.2011.10.009. Epub 2012 Jan 13. No abstract available. English, Spanish.</citation>
    <PMID>22245066</PMID>
  </results_reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 2, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>April 9, 2019</last_update_submitted>
  <last_update_submitted_qc>April 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tehran University of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Zinat Hatmi</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>melatonin</keyword>
  <keyword>inflammatory biomarkers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>In case of designing systematic reviews and according to Helsinki declaration might be shared.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 17, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT03764020/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03764020
org study id: TUMS
nct id: NCT03764020
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Since, lowering blood pressure (BP) in elevated blood pressure individuals represents an
      excellent opportunity to for primary prevention of hypertension (HTN). Therefore, it is
      planned to use a safe treatment option - oral melatonin supplementation - associated with
      lifestyle interventions according to the American college of cardiology/American heart
      association (ACC/AHA) 2013 guideline in elevated blood pressure individuals to mitigate
      systolic and diastolic BP and ultimately, to prevent the development of HTN.

      Hypothesis:

      Melatonin therapy can lower the systolic and diastolic BP of elevated blood pressure
      individuals Melatonin can attenuate levels of circulatory biomarkers of Hs- CRP, Cholesterol,
      LDL-c and triglyceride
Study design: Randomized controlled trial (RCT)

      Study population: Elevated blood pressure individuals who present themselves at the
      outpatient clinics of Tehran Heart Centre(THC) , seeking blood pressure treatment and who
      have a systolic blood pressure of 120-129 mmHg or a diastolic blood pressure of =80 mmHg.

      Treatment groups: Melatonin 3 mg versus placebo

      sample size: 160 per group ( 320 overall)

      Treatment allocation: After completing informed consent and prior to randomization, all
      participants undergo complete physical examination and laboratory test. Baseline levels of
      inflammatory biomarkers and pregnancy test (for women in reproductive age) will be performed.
      Sleep quality, actual sleep time, and sleep latency will be recorded.

      Treatment plan: Three weeks melatonin 3 Mg or placebo one hour before bedtime has been
      planned. All of the melatonin and placebo capsules will be supplied from a single hospital
      pharmacy and free of charge to the participants. Melatonin and placebo capsules will be
      identical. Participants will receive a three weeks supply at the assignment time. Besides,
      all participants will receive a careful plan of adherence to a heart-healthy diet, regular
      exercise, instruction for avoidance of tobacco use and maintenance of a healthy body mass
      index (BMI) according to 2013ACC/ AHA guideline.

      Follow up: Three weeks
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Melatonin 3 Mg or placebo associated with life style modification according to 2013ACC/ AHA guideline has been planned in parallel fashion for three weeks of follow up. Participants allocated to each group will stay at the same interventional group for entire follow up period of three weeks.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: Triple blinding is planned. All participants, medical providers and outcome evaluators will be blinded about treatment arms.
The THC pharmacy will dispense the medication and perform the randomization. Melatonin capsule and placebo will be completely identical.
measure: Mean change in systolic blood pressure from baseline
time frame: From enrollment to end of treatment at 3 weeks
description: Mean change in Systolic blood pressure from baseline in Millimeter Mercury, it measures average changes in systolic blood pressure. The best outcome value is < and =120 millimeter mercury. Systolic blood pressure ranges between 90-250 millimeter mercury.
measure: Mean change in diastolic blood pressure from baseline
time frame: From enrollment to end of treatment at 3 weeks
description: Mean change in diastolic blood pressure from baseline in Millimeter Mercury, it measures average changes in systolic blood pressure. The best outcome value is < 80 millimeter mercury. Diastolic blood pressure ranges between 60-140 millimeter mercury.
measure: Mean change in cholesterol
time frame: From enrollment to end of treatment at 3 weeks
description: Mean change in cholesterol in Milligram/deciliter from baseline, it measures average changes in cholesterol. The best outcome value is 200 milligram per deciliter. Total cholesterol less than 200 milligram per deciliter are considered desirable for adults. A reading between200-239 is considered borderline and a reading of 240 above is considered high.
measure: Mean change in low density lipoprotein
time frame: From enrollment to end of treatment at 3 weeks
description: Mean change in low density lipoprotein in Milligram/deciliter from baseline, it measures average changes in low density lipoprotein. The best outcome value is 100 milligram per deciliter. LDL level less than 100 milligram per deciliter is considered desirable, 100-130 borderline, 130-189 borderline high and above 190 is considered high.
measure: Mean change in fasting blood sugar
time frame: From enrollment to end of treatment at 3 weeks
description: Mean change in fasting blood sugar in Milligram/deciliter from baseline, it measures average changes in fasting blood sugar. Fasting blood sugar 72-99 milligram per deciliter is considered normal, 100-116 borderline and above 116 is considered high.
measure: Mean change in inflammatory biomarker
time frame: From enrollment to end of treatment at 3 weeks
description: Mean change in high sensitive C reactive protein (Hs-CRP) in Milligram/liter, it measures average changes in high sensitive C reactive protein (Hs-CRP). The best outcome value is <= 3 milligram per liter.
1-3 milligram per liter is considered normal and above 3 is considered high.
measure: Mean change in sleep quality score from baseline
time frame: From enrollment to end of treatment at 3 weeks
description: Mean change in Pittsburg sleep quality questionnaire in Likert numerical score from baseline, it measures average changes in sleep quality score. Pittsburg sleep quality questionnaire score of 5 or greater is indicative of poor sleep quality.
arm group label: Melatonin
arm group type: Experimental
description: Intervention group1:
Melatonin,capsule,3 mg, one dose one hour before bedtime, three weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Intervention group2 :
Placebo, capsule, 3 mg, one dose one hour before bedtime, for three weeks
intervention type: Drug
intervention name: Placebo oral capsule/placebo comparator
description: 3 mg placebo capsule one hour before bedtime for three weeks along with life style modification according to ACC/AHA 2013 guideline
arm group label: Placebo
other name: Placebo
intervention type: Drug
intervention name: Melatonin/experimental
description: Melatonin ,capsule, 3 mg, one dose one hour before bedtime, for three weeks along with life style modification according to ACC/AHA 2013 guideline.
arm group label: Melatonin
other name: Melatona
criteria: 
gender: All
minimum age: 30 Years
maximum age: 60 Years
healthy volunteers: No
last name: zinat Hatmi, Dr
role: Principal Investigator
affiliation: Tehran University of Medical Sciences
last name: zinat Hatmi
phone: +982164053219
email: hatmizn@sina.tums.ac.ir
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PMID: 12823612
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PMID: 21193011
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PMID: 12699131
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PMID: 14709797
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PMID: 12390508
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PMID: 20536686
citation: Arangino S, Cagnacci A, Angiolucci M, Vacca AM, Longu G, Volpe A, Melis GB. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol. 1999 May 1;83(9):1417-9. doi: 10.1016/s0002-9149(99)00112-5.
PMID: 10235107
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PMID: 9062865
citation: Cagnacci A, Arangino S, Angiolucci M, Maschio E, Melis GB. Influences of melatonin administration on the circulation of women. Am J Physiol. 1998 Feb;274(2):R335-8. doi: 10.1152/ajpregu.1998.274.2.R335.
PMID: 9486289
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PMID: 14732734
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PMID: 16364834
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PMID: 17000226
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PMID: 26632428
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PMID: 25126957
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PMID: 21138476
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PMID: 24650045
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PMID: 10792199
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PMID: 19876062
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PMID: 15722655
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citation: Pandi-Perumal SR, BaHammam AS, Ojike NI, Akinseye OA, Kendzerska T, Buttoo K, Dhandapany PS, Brown GM, Cardinali DP. Melatonin and Human Cardiovascular Disease. J Cardiovasc Pharmacol Ther. 2017 Mar;22(2):122-132. doi: 10.1177/1074248416660622. Epub 2016 Jul 27.
PMID: 27450357
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PMID: 22245066
responsible party type: Principal Investigator
investigator affiliation: Tehran University of Medical Sciences
investigator full name: Zinat Hatmi
investigator title: Professor
mesh term: Hypertension
mesh term: Melatonin
sharing ipd: Undecided
ipd description: In case of designing systematic reviews and according to Helsinki declaration might be shared.
provided document: 