search
Back to results

Trial of Oral Melatonin in Elevated Blood Pressure (MRCTEBP)

Primary Purpose

Elevated Blood Pressure

Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Placebo oral capsule/placebo comparator
Melatonin/experimental
Sponsored by
Tehran University of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Elevated Blood Pressure focused on measuring melatonin, inflammatory biomarkers

Eligibility Criteria

30 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Individuals with systolic blood pressure120-129 and/or diastolic blood pressure =80mmHg
  • Negative pregnancy test for women at productive age
  • Baseline melatonin and biomarkers level and complete liver function tests within normal range

Exclusion Criteria:

  • Previous history of hypersensitivity of melatonin
  • Past history of using antihypertensive treatment
  • Past medical history of hypertension, cardiovascular diseases, (i.e. coronary artery disease), and diabetes mellitus, epilepsy and other physician documented diseases
  • Use of beta-blockers, sleep aids, warfarin, flaxseed, soy and supplements

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Melatonin

    Placebo

    Arm Description

    Intervention group1: Melatonin,capsule,3 mg, one dose one hour before bedtime, three weeks

    Intervention group2 : Placebo, capsule, 3 mg, one dose one hour before bedtime, for three weeks

    Outcomes

    Primary Outcome Measures

    Mean change in systolic blood pressure from baseline
    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.
    Mean change in diastolic blood pressure from baseline
    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.
    Mean change in cholesterol
    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.
    Mean change in low density lipoprotein
    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.
    Mean change in fasting blood sugar
    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.
    Mean change in inflammatory biomarker
    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.

    Secondary Outcome Measures

    Mean change in sleep quality score from baseline
    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.

    Full Information

    First Posted
    November 27, 2018
    Last Updated
    April 9, 2019
    Sponsor
    Tehran University of Medical Sciences
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03764020
    Brief Title
    Trial of Oral Melatonin in Elevated Blood Pressure
    Acronym
    MRCTEBP
    Official Title
    A Triple Blinded Randomized Controlled Trial of Oral Melatonin in Elevated Blood Pressure Individual (MRCTEBP)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2019
    Overall Recruitment Status
    Unknown status
    Study Start Date
    June 1, 2019 (Anticipated)
    Primary Completion Date
    November 1, 2019 (Anticipated)
    Study Completion Date
    December 1, 2019 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Tehran University of Medical Sciences

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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
    Detailed Description
    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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Elevated Blood Pressure
    Keywords
    melatonin, inflammatory biomarkers

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    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.
    Masking
    ParticipantCare ProviderOutcomes 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.
    Allocation
    Randomized
    Enrollment
    320 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Melatonin
    Arm Type
    Experimental
    Arm Description
    Intervention group1: Melatonin,capsule,3 mg, one dose one hour before bedtime, three weeks
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Intervention group2 : Placebo, capsule, 3 mg, one dose one hour before bedtime, for three weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo oral capsule/placebo comparator
    Other Intervention Name(s)
    Placebo
    Intervention Description
    3 mg placebo capsule one hour before bedtime for three weeks along with life style modification according to ACC/AHA 2013 guideline
    Intervention Type
    Drug
    Intervention Name(s)
    Melatonin/experimental
    Other Intervention Name(s)
    Melatona
    Intervention 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.
    Primary Outcome Measure Information:
    Title
    Mean change in systolic blood pressure from baseline
    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.
    Time Frame
    From enrollment to end of treatment at 3 weeks
    Title
    Mean change in diastolic blood pressure from baseline
    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.
    Time Frame
    From enrollment to end of treatment at 3 weeks
    Title
    Mean change in cholesterol
    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.
    Time Frame
    From enrollment to end of treatment at 3 weeks
    Title
    Mean change in low density lipoprotein
    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.
    Time Frame
    From enrollment to end of treatment at 3 weeks
    Title
    Mean change in fasting blood sugar
    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.
    Time Frame
    From enrollment to end of treatment at 3 weeks
    Title
    Mean change in inflammatory biomarker
    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.
    Time Frame
    From enrollment to end of treatment at 3 weeks
    Secondary Outcome Measure Information:
    Title
    Mean change in sleep quality score from baseline
    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.
    Time Frame
    From enrollment to end of treatment at 3 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    30 Years
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Individuals with systolic blood pressure120-129 and/or diastolic blood pressure =80mmHg Negative pregnancy test for women at productive age Baseline melatonin and biomarkers level and complete liver function tests within normal range Exclusion Criteria: Previous history of hypersensitivity of melatonin Past history of using antihypertensive treatment Past medical history of hypertension, cardiovascular diseases, (i.e. coronary artery disease), and diabetes mellitus, epilepsy and other physician documented diseases Use of beta-blockers, sleep aids, warfarin, flaxseed, soy and supplements
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    zinat Hatmi
    Phone
    +982164053219
    Email
    hatmizn@sina.tums.ac.ir
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    zinat Hatmi, Dr
    Organizational Affiliation
    Tehran University of Medical Sciences
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided
    IPD Sharing Plan Description
    In case of designing systematic reviews and according to Helsinki declaration might be shared.
    Citations:
    PubMed Identifier
    12823612
    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.
    Results Reference
    background
    PubMed Identifier
    21193011
    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.
    Results Reference
    background
    PubMed Identifier
    12699131
    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.
    Results Reference
    background
    PubMed Identifier
    14709797
    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.
    Results Reference
    background
    PubMed Identifier
    12390508
    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.
    Results Reference
    background
    PubMed Identifier
    20536686
    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.
    Results Reference
    background
    PubMed Identifier
    10235107
    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.
    Results Reference
    background
    PubMed Identifier
    9062865
    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.
    Results Reference
    background
    PubMed Identifier
    9486289
    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.
    Results Reference
    background
    PubMed Identifier
    14732734
    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.
    Results Reference
    background
    PubMed Identifier
    16364834
    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.
    Results Reference
    background
    PubMed Identifier
    17000226
    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.
    Results Reference
    background
    PubMed Identifier
    26632428
    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.
    Results Reference
    background
    PubMed Identifier
    25126957
    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.
    Results Reference
    background
    PubMed Identifier
    21138476
    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.
    Results Reference
    background
    PubMed Identifier
    24650045
    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.
    Results Reference
    background
    PubMed Identifier
    10792199
    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.
    Results Reference
    background
    PubMed Identifier
    19876062
    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.
    Results Reference
    background
    PubMed Identifier
    15722655
    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.
    Results Reference
    background
    PubMed Identifier
    27965209
    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.
    Results Reference
    background
    PubMed Identifier
    23172989
    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.
    Results Reference
    background
    PubMed Identifier
    27450357
    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.
    Results Reference
    result
    PubMed Identifier
    22245066
    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.
    Results Reference
    result

    Learn more about this trial

    Trial of Oral Melatonin in Elevated Blood Pressure

    We'll reach out to this number within 24 hrs