Contribution of Angiotensin II to Supine Hypertension in Autonomic Failure

NCT01292694 | Terminated Phase 1

• 1 other identifier: 101618
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertension; Pure Autonomic Failure; Multiple System Atrophy

Keywords

supine hypertension; autonomic failure; angiotensin; losartan; captopril

Outcome Measures

Primary Outcomes (1)

• Changes in plasma renin activity and subsequent components of the circulating renin-angiotensin system

  Changes in supine plasma renin activity and aldosterone following drug administration

  0 - 6 hours post administration

Secondary Outcomes (2)

• Changes in blood pressure

  0 - 6 hours post administration

• Changes in heart rate, cardiac output, stroke volume and systemic vascular resistance

  0 - 6 hours post administration

Study Arms (3)

Losartan

EXPERIMENTAL

Angiotensin II AT1 receptor antagonist which blocks the actions of angiotensin II

Drug: Losartan

Captopril

EXPERIMENTAL

ACE inhibitor which blocks the formation of angiotensin II

Drug: Captopril

Placebo Tablet

PLACEBO COMPARATOR

A placebo tablet will be provided by the Vanderbilt Investigational Drug Service for these studies.

Drug: Placebo

Interventions

Losartan DRUG

Oral, single-dose, 50 mg tablet

Also known as: Cozaar

Losartan

Captopril DRUG

Oral, single-dose, 50 mg tablet

Also known as: Capoten

Captopril

Placebo DRUG

Oral, single administration, gelatin capsule filled with microcrystalline cellulose

Placebo Tablet

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Hypertension; Pure Autonomic Failure; Multiple System Atrophy

Interventions

Losartan; Captopril

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Proline; Imino Acids; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Italo Biaggioni, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Associate Director Clinical Research Center

Study Record Dates

• First Submitted: February 8, 2011
• First Posted: February 9, 2011
• Study Start: March 1, 2011
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: August 24, 2018

Record last verified: 2018-08

Locations

US (1)