View Clinical Trial (Medical Research Study)
Contribution of Angiotensin II to Supine Hypertension in Autonomic Failure
| City: |
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Nashville |
| State: |
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Tennessee |
| Zip Code: |
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37232 |
| Conditions: |
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Hypertension - Pure Autonomic Failure - Multiple System Atrophy |
| Purpose: |
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The purpose of this study is to test the hypothesis that angiotensin II plays a role in the
supine hypertension of primary autonomic failure. To determine the contribution of
angiotensin II to renin and blood pressure regulation in autonomic failure, patients with
multiple system atrophy [MSA] or pure autonomic failure [PAF] and supine hypertension will
undergo medication testing with the angiotensin II receptor blocker losartan. The
investigators will compare the biochemical and hemodynamic effects between MSA and PAF
patients. In a subset of patients, the investigators will also give the ACE inhibitor
captopril. Our primary endpoint will be changes in plasma renin activity, and subsequent
components of the circulating renin-angiotensin system, in response to angiotensin II
blockade. Our secondary outcome will be changes in hemodynamic measures during
administration of these drugs.
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| Study Summary: |
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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.
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| Criteria: |
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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
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| NCT ID: |
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NCT01292694 |
| Primary Contact: |
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Principal Investigator
Italo Biaggioni, MD
Vanderbilt University
Bonnie K Black, RN
Phone: 615-322-3304
Email: adcresearch@vanderbilt.edu
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| Backup Contact: |
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N/A |
| Location Contact: |
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Nashville, Tennessee 37232
United States
Bonnie K Black, RN
Phone: 615-322-3304
Email: adcresearch@vanderbilt.edu
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 25, 2013 |
| Modifications to this listing: |
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