Trial of Oral Melatonin in Elevated Blood Pressure

NCT03764020 | Unknown Phase 3

• 1 other identifier: TUMS
• Study Type: interventional
• Target: 320
• Locations: 0 countries
• Sites: N/A

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

Conditions

Elevated Blood Pressure

Keywords

melatonin; inflammatory biomarkers

Outcome Measures

Primary Outcomes (6)

• 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.

  From enrollment to end of treatment at 3 weeks

• 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.

  From enrollment to end of treatment at 3 weeks

• 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.

  From enrollment to end of treatment at 3 weeks

• 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.

  From enrollment to end of treatment at 3 weeks

• 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.

  From enrollment to end of treatment at 3 weeks

• 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.

  From enrollment to end of treatment at 3 weeks

Secondary Outcomes (1)

• Mean change in sleep quality score from baseline

  From enrollment to end of treatment at 3 weeks

Study Arms (2)

Melatonin

EXPERIMENTAL

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

Drug: Melatonin/experimental

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo oral capsule/placebo comparator

Interventions

Placebo oral capsule/placebo comparator DRUG

3 mg placebo capsule one hour before bedtime for three weeks along with life style modification according to ACC/AHA 2013 guideline

Also known as: Placebo

Placebo

Melatonin/experimental DRUG

Melatonin ,capsule, 3 mg, one dose one hour before bedtime, for three weeks along with life style modification according to ACC/AHA 2013 guideline.

Also known as: Melatona

Melatonin

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tehran University of Medical Sciences: lead

Related Publications (23)

• 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.

  PMID: 12823612 BACKGROUND

• 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.

  PMID: 21193011 BACKGROUND

• 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.

  PMID: 12699131 BACKGROUND

• 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.

  PMID: 14709797 BACKGROUND

• 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.

  PMID: 12390508 BACKGROUND

• 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.

  PMID: 20536686 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 9062865 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 14732734 BACKGROUND

• 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.

  PMID: 16364834 BACKGROUND

• 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.

  PMID: 17000226 BACKGROUND

• 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.

  PMID: 26632428 BACKGROUND

• 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.

  PMID: 25126957 BACKGROUND

• 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.

  PMID: 21138476 BACKGROUND

• 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.

  PMID: 24650045 BACKGROUND

• 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.

  PMID: 10792199 BACKGROUND

• 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.

  PMID: 19876062 BACKGROUND

• 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.

  PMID: 15722655 BACKGROUND

• 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.

  PMID: 27965209 BACKGROUND

• 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.

  PMID: 23172989 BACKGROUND

• 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 RESULT

• 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.

  PMID: 22245066 RESULT

MeSH Terms

Conditions

Hypertension

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• zinat Hatmi, Dr

  Tehran University of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

zinat Hatmi

CONTACT

+982164053219; hatmizn@sina.tums.ac.ir

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: December 4, 2018
• Study Start: June 1, 2019
• Primary Completion: November 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 10, 2019

Record last verified: 2019-04