临床试验/NCT00223717

NCT00223717已完成1 期

The Pathophysiology and Treatment of Supine Hypertension in Patients With Autonomic Failure

Vanderbilt University1 个研究点分布在 1 个国家目标入组 152 人开始时间: 2001年1月最近更新: 2017年10月13日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Vanderbilt University
入组人数: 152
试验地点: 1
主要终点: Decrease in supine systolic blood pressure

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Supine hypertension is a common problem that affects at least 50% of patients with primary autonomic failure. Supine hypertension can be severe, and complicates the treatment of orthostatic hypotension. Drugs used for the treatment of orthostatic hypotension (eg, fludrocortisone and pressor agents), worsen supine hypertension. High blood pressure may also cause target organ damage in this group of patients. The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure have not been defined.

In a study, we, the investigators at Vanderbilt University, examined 64 patients with AF, 29 with pure autonomic failure (PAF) and 35 with multiple system atrophy (MSA). 66% of patients had supine systolic (systolic blood pressure [SBP] > 150 mmHg) or diastolic (diastolic blood pressure [DBP] > 90 mmHg) hypertension (average blood pressure [BP]: 179 ± 5/89 ± 3 mmHg in 21 PAF and 175 ± 5/92 ± 3 mmHg in 21 MSA patients). Plasma norepinephrine (92 ± 15 pg/mL) and plasma renin activity (0.3 ± 0.05 ng/mL per hour) were very low in a subset of patients with AF and supine hypertension. (Shannon et al., 1997).

Our group has showed that a residual sympathetic function contributes to supine hypertension in patients with severe autonomic failure and that this effect is more prominent in patients with MSA than in those with PAF (Shannon et al., 2000). MSA patients had a marked depressor response to low infusion rates of trimethaphan, a ganglionic blocker; the response in PAF patients was more variable. At 1 mg/min, trimethaphan decreased supine SBP by 67 +/- 8 and 12 +/- 6 mmHg in MSA and PAF patients, respectively (P < 0.0001). MSA patients with supine hypertension also had greater SBP response to oral yohimbine, a central alpha2 receptor blocker, than PAF patients. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. This result suggests that residual sympathetic activity drives supine hypertension in MSA; in contrast, supine hypertension in PAF.

It is hoped that from this study will emerge a complete picture of the supine hypertension of autonomic failure. Understanding the mechanism of this paradoxical hypertension in the setting of profound loss of sympathetic function will improve our approach to the treatment of hypertension in autonomic failure, and it could also contribute to our understanding of hypertension in general.

详细描述

Overnight Medication Trials:

Patients will be studied on the GCRC while in 150 mEq/day sodium balance and on a diet free of substances which interfere with catecholamine determination. Subjects will be asked to use the bathroom to empty their bladder at 8:00 PM. They will be given a randomly chosen medication aliskiren (Tekturna) 150-300mg po, bosentan (Tracleer) 62.5 -125 mg po, captopril 25-50mg po, carbidopa 25-200mg po, clonidine 0.1-0.2mg po, desmopressin 0.2 - 0.6mg po (DDAVP), -diltiazem 30-60 mg po, dipyridamole 200 mg and aspirin 25 mg po (Aggrenox), eplerenone (Inspra) 50-100 mg po, guanfacine (Tenex) 1-3 mg po, hydralazine 10-50 mg po, hydrochlorothiazide 12.5-100 mg po, L- arginine 6-17 g po, losartan 25-100mg po, metoprolol tartrate (Lopressor) 25-100 mg po, nebivolol hydrochloride (Bystolic) 2.5-40 mg po, nitroglycerin-transdermal 0.05-0.2 mg patch, nifedipine (adalat) doses 10-30 mg, prazosin hydrochloride 0.5-1 mg po, sildenafil (Viagra) 25- 100 mg po, tamsulosin hydrochloride (Flomax) 0.4-0.8 mg po. The combination desmopressin 0.2 mg po (DDAVP) and nitroglycerin-transdermal 0.05-0.2 mg. The combinations desmopressin 0.2 mg po and nifedipine (10-30 mg). A placebo pill or skin patch will be done as a control to measure their supine blood pressure without medication intervention. They will then be asked to lie down with the head of the bed elevated 10 degrees. An automated blood pressure cuff (Dinamap) will be wrapped around an upper arm and blood pressure will be measured automatically 2 times in a row every 2 hours. At 8 AM the following morning the study ends. The subjects will then stand at the bedside as motionless as possible for 30 minutes for blood pressure and heart rate determination.

Urine will be collected for 24 hours for determination of volume and sodium, potassium and catecholamines (for some medication trials) in 12 hour segments, from 8 a.m. to 8 p.m. and 8 p.m. to 8 a.m. to ascertain how the medications affect urine production.

For medication trials affecting renal Na and/or water regulation (e.g. desmopressin, carbidopa), blood samples will be collected (5 mL, 1 teaspoon) at 8 PM and 8 AM for determination of a basic metabolic panel.

Raising the head of the bed during the night is a non-pharmacologic measure that may reduce supine blood pressure, nocturnal natriuresis and improve orthostatic hypotension the following morning in autonomic failure patients with supine hypertension. However, it is not known if tilting the bed with the head up is better than raising only the head of the bed. To compare the effect of these two ways of raising the head of the bed on nighttime blood pressure and nocturnal natriuresis, some patients will undergo two additional tests. On two separate nights (either consecutive or not), patients will receive the placebo and will be assigned by simple randomization to lie down in one of two different bed positions:

The head of the bed elevated 10 degrees (~ 7 inches); or
The whole bed tilted head-up 5 degrees in reverse trendelenburg (head of the bed elevated ~7 inches).

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Treatment
盲法: Single (Participant)

入排标准

年龄范围: 18 Years 至 80 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Patients with autonomic failure and with supine hypertension from all races

排除标准

•All medical students
•Pregnant women
•High-risk patients (e.g. heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction)
•History of serious allergies or asthma.

研究组 & 干预措施

1: Active drug or intervention

结局指标

主要结局

Decrease in supine systolic blood pressure

时间窗: 12 hours

次要结局

Decrease in pressure natriuresis(12 hours)

研究者

发起方

Vanderbilt University

申办方类型

Other

责任方

Principal Investigator

主要研究者

Italo Biaggioni

Professor of Medicine and Pharmacology

Vanderbilt University

研究点 (1)

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