Study MIPAE - Melatonin and Essential Arterial Hypertension

NCT05257291 | Unknown Phase 2

• 1 other identifier: NP 2717
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Essential Hypertension

Keywords

Essential Hypertension; Melatonin; Antioxidant; Antihypertensive; Cardiovascular System

Outcome Measures

Primary Outcomes (14)

• Blood pressure.

  Value of ambulatory blood pressure obtained from the mean of three different misurations.

  Baseline.

• Heart rate.

  Ambulatory recorder of the heart rate of the patient.

  Baseline.

• Endothelial parameters.

  PAT signals were obtained using the EndoPAT-2000 device, which has been vali-dated and used previously to assess peripheral arterial tone in other populations. Endothelial function is measured via a reactive hyper-emia (RH) protocol: it consists of a 5 minutes baseline mea-surement, after which a blood pressure cuff on the test arm isinflated to 60 mm Hg above baseline systolic BP or at least200 mm Hg for 5 minutes. After 5 minutes, the cuff is deflated, and the PAT tracing isrecorded for a further 5 minutes. The cal-culated ratio is called RH-PAT index or RH index (RHI).

  Baseline.

• Arterial stiffness parameters.

  The radial artery waveform was recorded using the SphygmoCor system. The tip of the tonometer was pressed gently against the radial artery at the site of maximum pulsation at the wrist. This micromanometer precisely records pressure within the artery. he augmentation pressure is defined as the height of the late systolic peak above the inflection point. Augmentation index is expressed as a percentage of PPAO. Augmentation index is a measure of the stiffness of the arterial walls, namely pulsatile load. Because there is a linear relationship between it and heart rate (HR), augmentation index was standardized to a HR of 75 bpm (AIx@75).

  Baseline.

• Echocardiographic parameters.

  Bi-dimensional transthoracic echocardiographic examinations were performed using Vivid 9 and Vivid Q (GE Medical HealthCare, USA) with a probe of 3.5 MHz, to assess LV dimensions and systolic function, according to the guidelines. The main points were: the dimensions of atria and ventricles, stenosis and valve insufficiencies, systolic and diastolic function VS and VD, Dimensions and elastic properties of the ascending aorta (compliance, distensibility, stiffness index, elastic modulus of Peterson, PWV, M-mode strain, tissue strain).

  Baseline.

• Plasmatic melatonin levels.

  Obtained with ELISA laboratory test.

  Baseline.

• Total circulating antioxidant capacity in plasma.

  Obtained with ELISA laboratory test.

  Baseline.

• Blood pressure.

  Ambulatory blood pressure obtained from the mean of three different misurations.

  1 year.

• Heart rate.

  Ambulatory recorder of the heart rate of the patient.

  1 year.

• Endothelial parameters.

  PAT signals were obtained using the EndoPAT-2000 device, which has been vali-dated and used previously to assess peripheral arterial tone in other populations. Endothelial function is measured via a reactive hyper-emia (RH) protocol: it consists of a 5 minutes baseline mea-surement, after which a blood pressure cuff on the test arm isinflated to 60 mm Hg above baseline systolic BP or at least200 mm Hg for 5 minutes. After 5 minutes, the cuff is deflated, and the PAT tracing isrecorded for a further 5 minutes. The cal-culated ratio is called RH-PAT index or RH index (RHI).

  1 year.

• Arterial stiffness parameters.

  The radial artery waveform was recorded using the SphygmoCor system. The tip of the tonometer was pressed gently against the radial artery at the site of maximum pulsation at the wrist. This micromanometer precisely records pressure within the artery. he augmentation pressure is defined as the height of the late systolic peak above the inflection point. Augmentation index is expressed as a percentage of PPAO. Augmentation index is a measure of the stiffness of the arterial walls, namely pulsatile load. Because there is a linear relationship between it and heart rate (HR), augmentation index was standardized to a HR of 75 bpm (AIx@75).

  1 year.

• Echocardiographic parameters.

  Bi-dimensional transthoracic echocardiographic examinations were performed using Vivid 9 and Vivid Q (GE Medical HealthCare, USA) with a probe of 3.5 MHz, to assess LV dimensions and systolic function, according to the guidelines. The main points were: the dimensions of atria and ventricles, stenosis and valve insufficiencies, systolic and diastolic function VS and VD, Dimensions and elastic properties of the ascending aorta (compliance, distensibility, stiffness index, elastic modulus of Peterson, PWV, M-mode strain, tissue strain).

  1 year.

• Plasmatic melatonin levels.

  Obtained with ELISA laboratory test.

  1 year.

• Total circulating antioxidant capacity in plasma.

  Obtained with ELISA laboratory test.

  1 year.

Study Arms (2)

Control group

NO INTERVENTION

Group of essential hypertensive patients who have received no additional therapies in addition to their established treatment plan (each patient was on specific antihypertensive therapy that has not been changed).

Melatonin treated group

ACTIVE COMPARATOR

Group of essential hypertensive patients who have received additional therapies consisting in 1 mg/day of melatonin for 1 year, in addition to their established treatment plan.

Drug: Melatonin

Interventions

Melatonin DRUG

Supplementation with 1 mg/day of melatonin for 1 year

Melatonin treated group

Eligibility Criteria

• Age: 40 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Caucasian race;
• Age 40-50;
• Signed written informed consent
• Normal weight;
• Blood pressure: PAD \>90 mmHg and PAS \>140 mmHg;
• Blood pressure in the above mentioned range from at least 1 years
• Fasting blood sugar \< 100 mg/dL;
• Total cholesterol \< 200 mg/dL and triglycerides \< 150 mg/dL;
• Intake of antihypertensive therapies (except nitrates, statins and β-blockers);
• Non-smoking;
• No night shift workers (at least in the last 3 months before recruitment);
• With a regular sleep/wake rhythm;
• No pregnant/nursing women.

You may not qualify if:

• Blood pressure: PAD \<90 mmHg and PAS \<140 mmHg
• Heart disease of any kind;
• Autoimmune or rheumatological or vascular diseases other than essential hypertension;
• Anti-hypertensive therapies with nitrates, statins or β-blockers;
• Pregnancy/nursing;
• \< 40 or \> 50 years;
• Worker with night shifts (for a period of less than 3 months before recruitment);
• Continuous irregular sleep/wake rhythm.

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

Anatomy and Physiopathology Division, Department of Experimental and Clinical Sciences, University of Brescia (Italy), Viale Europa 11, 25123 Brescia, Italy

Brescia, 23125, Italy

Location

Related Publications (25)

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• 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.

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• 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.

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• 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.

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MeSH Terms

Conditions

Essential Hypertension

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Hypertension; 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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Full Professor of Human Anatomy

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: February 25, 2022
• Study Start: February 2, 2018
• Primary Completion: July 14, 2022
• Study Completion: August 1, 2024
• Last Updated: February 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: illimited
• Access Criteria: upon request

Locations

IT (1)