Melatonin and Essential Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Blood pressure.
研究概览
简要总结
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.
详细描述
Hypertension is a pathological condition characterized by a constant and not occasional increase in systolic and diastolic blood pressure values. This pathology represents one of the most important public health problems in industrialized countries, as it affects more than 25-30% of the adult population and can cause serious and even fatal complications. It is in fact considered the major risk factor of mortality and pathological effect at cardiovascular, encephalic and renal level.
The classification of hypertension suggested by the ESC/ESH Guidelines defines diastolic blood pressure (PAD) values of 80-84 mmHg and systolic blood pressure (PAS) values of 120-129 mmHg as "normal" in a healthy adult. Blood pressure values between 90-99 mmHg (PAD) and 140-159 mmHg (PAS) define grade 1 hypertension.Between 100-109 mmHg (PAD) and 160-179 mmHg (PAS) define grade 2 hypertension. For values above 110 mmHg (PAD) and 180 mmHg (PAS), determine grade 3 hypertension (after 60 years of age slightly higher values are accepted). Although many antihypertensive drug therapies exist today, patients often show a lack of response to pharmacological treatment due to numerous factors of both genetic and environmental nature that contribute to determine the clinical picture and the poor response to the set therapeutic regime. Recent studies aimed at clarifying the pathophysiology of resistant hypertension are highlighting new pathophysiological mechanisms potentially involved in the genesis of this clinical condition. Since essential hypertension and vascular and cardiac dysfunctions seem to be closely related, the identification of molecules/substances that can at least help to reduce the alterations induced by the pathogenetic process of essential hypertension is a priority. In recent years, melatonin has shown important and interesting antihypertensive therapeutic potential. It has also been demonstrated by some authors of this project, in an animal model of arterial hypertension, that melatonin, thanks to its antioxidant properties, is able to regress structural alterations of both the aorta and small mesenteric resistance arteries in an animal model of arterial hypertension.
It is therefore necessary to investigate, also in humans, the correlation among essential arterial hypertension, levels of circulating melatonin and onset of cardiovascular events.
Furthermore, it is of fundamental importance to remember that, to date, following treatment with melatonin, even at high doses, show only rare and minimal adverse effects, including daytime drowsiness, dizziness and headaches.
The aim of the study was, therefore, to evaluate the antihypertensive, antioxidant and vasoprotective effects of melatonin in adult patients suffering from at least 1 year essential hypertension and in antihypertensive therapy. In a broad sense, the aim will be to contribute to current knowledge in terms of effective treatment and reduced impact of cardiovascular changes related to hypertension.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Melatonin treated group
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.
干预措施: Melatonin (Drug)
结局指标
主要结局
Blood pressure.
时间窗: 1 year.
Ambulatory blood pressure obtained from the mean of three different misurations.
Heart rate.
时间窗: 1 year.
Ambulatory recorder of the heart rate of the patient.
Endothelial parameters.
时间窗: 1 year.
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).
Arterial stiffness parameters.
时间窗: 1 year.
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).
Plasmatic melatonin levels.
时间窗: 1 year.
Obtained with ELISA laboratory test.
Echocardiographic parameters.
时间窗: 1 year.
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).
Total circulating antioxidant capacity in plasma.
时间窗: 1 year.
Obtained with ELISA laboratory test.
次要结局
未报告次要终点
研究者
Rita Rezzani
PhD, Full Professor of Human Anatomy
Università degli Studi di Brescia