Study MIPAE - Melatonin and Essential Arterial Hypertension

Summary

Study MIPAE - Melatonin and essential arterial hypertension. Study with dietary supplement, prospective and monocentric (randomized control trial). 1 mg/day of melatonin has been administered for one year to a group of patients suffering from essential hypertension (from at least one year) and who are already on antihypertensive therapy. This group has been compared with as many hypertensive patients on antihypertensive therapy to whom melatonin has not been administered. Each of the participants have been evaluated at the beginning of the study and after one year considering: * systolic and diastolic blood pressure; * echocardiographic values (Vivid Q, GE Healthcare); * applanation tonometry (SphygmoCor, AtCor Medical); * peripheral arterial tonometry (EndoPAT-2000, Itamar); * melatonin levels and total circulating antioxidant capacity after peripheral venous blood sampling. The aim of the study was to evaluate the antioxidant and vasoprotective effects of melatonin, evaluating both plasma changes and directly studying the possibility of a real remodeling and improvement of cardiac structures.

Timeline

Start

2018-02-02

Primary completion

2022-07-14

Completion

2024-08

Publications

• Background Acuna-Castroviejo D, Escames G, Venegas C, Diaz-Casado ME, Lima-Cabello E, Lopez LC, Rosales-Corral S, Tan DX, Reiter RJ. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci. 2014 Aug;71(16):2997-3025. doi: 10.1007/s00018-014-1579-2. Epub 2014 Feb 20.
• Background Agabiti-Rosei C, De Ciuceis C, Rossini C, Porteri E, Rodella LF, Withers SB, Heagerty AM, Favero G, Agabiti-Rosei E, Rizzoni D, Rezzani R. Anticontractile activity of perivascular fat in obese mice and the effect of long-term treatment with melatonin. J Hypertens. 2014 Jun;32(6):1264-74. doi: 10.1097/HJH.0000000000000178.
• Background 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.
• 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.
• Background Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):168-75. doi: 10.1161/01.atv.0000051384.43104.fc.
• 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.
• Background Cagnacci A, Arangino S, Angiolucci M, Melis GB, Facchinetti F, Malmusi S, Volpe A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clin Endocrinol (Oxf). 2001 Feb;54(2):261-6. doi: 10.1046/j.1365-2265.2001.01204.x.
• Background Chen CH, Fetics B, Nevo E, Rochitte CE, Chiou KR, Ding PA, Kawaguchi M, Kass DA. Noninvasive single-beat determination of left ventricular end-systolic elastance in humans. J Am Coll Cardiol. 2001 Dec;38(7):2028-34. doi: 10.1016/s0735-1097(01)01651-5.
• Background Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni JM. Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res. 2000 May;28(4):193-202. doi: 10.1034/j.1600-079x.2000.280401.x.
• Background Favero G, Rodella LF, Reiter RJ, Rezzani R. Melatonin and its atheroprotective effects: a review. Mol Cell Endocrinol. 2014 Feb 15;382(2):926-37. doi: 10.1016/j.mce.2013.11.016. Epub 2013 Nov 28.
• Background Goor DA, Sheffy J, Schnall RP, Arditti A, Caspi A, Bragdon EE, Sheps DS. Peripheral arterial tonometry: a diagnostic method for detection of myocardial ischemia induced during mental stress tests: a pilot study. Clin Cardiol. 2004 Mar;27(3):137-41. doi: 10.1002/clc.4960270307.
• 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.
• Background Intengan HD, Schiffrin EL. Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension. 2001 Sep;38(3 Pt 2):581-7. doi: 10.1161/hy09t1.096249.
• Background Kawasaki T, Sasayama S, Yagi S, Asakawa T, Hirai T. Non-invasive assessment of the age related changes in stiffness of major branches of the human arteries. Cardiovasc Res. 1987 Sep;21(9):678-87. doi: 10.1093/cvr/21.9.678.
• Background Laurent S, Boutouyrie P. The structural factor of hypertension: large and small artery alterations. Circ Res. 2015 Mar 13;116(6):1007-21. doi: 10.1161/CIRCRESAHA.116.303596.
• Background Lundberg MS, Crow MT. Age-related changes in the signaling and function of vascular smooth muscle cells. Exp Gerontol. 1999 Jul;34(4):549-57. doi: 10.1016/s0531-5565(99)00036-4.
• Background Meissner A, Minnerup J, Soria G, Planas AM. Structural and functional brain alterations in a murine model of Angiotensin II-induced hypertension. J Neurochem. 2017 Feb;140(3):509-521. doi: 10.1111/jnc.13905. Epub 2016 Dec 21.
• Background Nawaz W, Khan FU, Khan MZ, Gang W, Yang M, Liao X, Zhang L, Ihsan AU, Khan A, Han L, Zhou X. Exo-organoplasty interventions: A brief review of past, present and future directions for advance heart failure management. Biomed Pharmacother. 2017 Apr;88:162-172. doi: 10.1016/j.biopha.2017.01.048. Epub 2017 Jan 16.
• Background Oktay AA, Lavie CJ, Milani RV, Ventura HO, Gilliland YE, Shah S, Cash ME. Current Perspectives on Left Ventricular Geometry in Systemic Hypertension. Prog Cardiovasc Dis. 2016 Nov-Dec;59(3):235-246. doi: 10.1016/j.pcad.2016.09.001. Epub 2016 Sep 8.
• Background Orabona R, Sciatti E, Vizzardi E, Bonadei I, Valcamonico A, Metra M, Frusca T. Endothelial dysfunction and vascular stiffness in women with previous pregnancy complicated by early or late pre-eclampsia. Ultrasound Obstet Gynecol. 2017 Jan;49(1):116-123. doi: 10.1002/uog.15893.
• Background Rezzani R, Porteri E, De Ciuceis C, Bonomini F, Rodella LF, Paiardi S, Boari GE, Platto C, Pilu A, Avanzi D, Rizzoni D, Agabiti Rosei E. Effects of melatonin and Pycnogenol on small artery structure and function in spontaneously hypertensive rats. Hypertension. 2010 Jun;55(6):1373-80. doi: 10.1161/HYPERTENSIONAHA.109.148254. Epub 2010 Apr 26.
• Background Rizzoni D, Porteri E, De Ciuceis C, Boari GE, Zani F, Miclini M, Paiardi S, Tiberio GA, Giulini SM, Muiesan ML, Castellano M, Rosei EA. Lack of prognostic role of endothelial dysfunction in subcutaneous small resistance arteries of hypertensive patients. J Hypertens. 2006 May;24(5):867-73. doi: 10.1097/01.hjh.0000222756.76982.53.
• Background Sarkar T, Singh NP. Epidemiology and Genetics of Hypertension. J Assoc Physicians India. 2015 Sep;63(9):61-98.
• Background Scuteri A, Nilsson PM, Tzourio C, Redon J, Laurent S. Microvascular brain damage with aging and hypertension: pathophysiological consideration and clinical implications. J Hypertens. 2011 Aug;29(8):1469-77. doi: 10.1097/HJH.0b013e328347cc17.
• Background Sorriento D, Santulli G, Del Giudice C, Anastasio A, Trimarco B, Iaccarino G. Endothelial cells are able to synthesize and release catecholamines both in vitro and in vivo. Hypertension. 2012 Jul;60(1):129-36. doi: 10.1161/HYPERTENSIONAHA.111.189605. Epub 2012 Jun 4.

Drugs

Indications