- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01292694
Contribution of Angiotensin II to Supine Hypertension in Autonomic Failure
Study Overview
Status
Intervention / Treatment
Detailed Description
Primary autonomic failure is a disabling condition characterized by orthostatic hypotension. It is less well appreciated that at least 50% of these patients have high blood pressure when lying down [supine hypertension]. The mechanisms underlying supine hypertension in autonomic failure remain poorly understood. The hypertension in MSA patients may be explained by residual sympathetic tone, possibly acting on hypersensitive adrenoreceptors and unrestrained by the lack of baroreflex modulation. In contrast, the hypertension in PAF is associated with increased vascular resistance in the absence of residual sympathetic tone. However, the factors driving an elevation in either sympathetic or vascular tone in these patients remain unclear.
The investigators hypothesize that angiotensin II, a hormone widely implicated in blood pressure regulation, plays a role in the supine hypertension of autonomic failure. To determine the contribution of angiotensin II to renin and blood pressure regulation in autonomic failure, the investigators will administer the angiotensin II receptor blocker losartan to MSA and PAF patients with supine hypertension. The primary endpoint will be changes in plasma renin activity, and subsequent components of the circulating renin-angiotensin system, in response to angiotensin II blockade. The secondary outcomes will be the decrease in blood pressure and changes in heart rate, cardiac output, stroke volume and systemic vascular resistance during administration of these drugs.
Subjects will be studied on 2 separate days, one with oral administration of placebo and the other with losartan [50 mg]. The order of administration will be randomized in a single-blind manner. The investigators will collect blood samples before and every 2 hours after administration for up to 6 hours to determine if angiotensin II regulates plasma renin activity, and other components of the circulating renin-angiotensin system, in autonomic failure. The investigators will also obtain hemodynamic measurements before and every 1 hour (blood pressure and heart rate) or 2 hours (cardiac output, stroke volume and systemic vascular resistance) after drug administration.
In a subset of patients the investigators will also administer the ACE inhibitor captopril [50 mg] on a separate study day using the same methods. Captopril is less specific for assessing the role of angiotensin II to hypertension. However, it may provide important information on the mechanism for angiotensin II formation in these patients.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with autonomic failure who exhibit supine hypertension and are in the hospital already participating in the study "The Evaluation and Treatment of Autonomic Failure [IRB # 000814]
- Supine hypertension, defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mm Hg
- Males and females of all races, between 18 to 85 years of age
- Able and willing to provide informed consent with the understanding that they may withdraw consent at any time without prejudice to future medical care
Exclusion Criteria:
- All medical students
- Pregnant women
- Patients with a history of angioedema
- Patients with a known allergy to any ACE inhibitor or angiotensin receptor blocker
- High-risk patients [e.g. heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction]
- Patients with hemoglobin < 10.5 [or hematocrit < 32]
- Inability to give, or withdraw, informed consent
- Other factors which in the investigator's opinion would prevent the patient from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Losartan
Angiotensin II AT1 receptor antagonist which blocks the actions of angiotensin II
|
Oral, single-dose, 50 mg tablet
Other Names:
|
Experimental: Captopril
ACE inhibitor which blocks the formation of angiotensin II
|
Oral, single-dose, 50 mg tablet
Other Names:
|
Placebo Comparator: Placebo Tablet
A placebo tablet will be provided by the Vanderbilt Investigational Drug Service for these studies.
|
Oral, single administration, gelatin capsule filled with microcrystalline cellulose
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in plasma renin activity and subsequent components of the circulating renin-angiotensin system
Time Frame: 0 - 6 hours post administration
|
Changes in supine plasma renin activity and aldosterone following drug administration
|
0 - 6 hours post administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in blood pressure
Time Frame: 0 - 6 hours post administration
|
Changes in supine blood pressure following drug administration
|
0 - 6 hours post administration
|
Changes in heart rate, cardiac output, stroke volume and systemic vascular resistance
Time Frame: 0 - 6 hours post administration
|
Changes in supine systemic hemodynamics following drug administration
|
0 - 6 hours post administration
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Autonomic Nervous System Diseases
- Primary Dysautonomias
- Hypotension
- Hypertension
- Multiple System Atrophy
- Shy-Drager Syndrome
- Pure Autonomic Failure
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Enzyme Inhibitors
- Protease Inhibitors
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Angiotensin-Converting Enzyme Inhibitors
- Losartan
- Captopril
Other Study ID Numbers
- 101618
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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