Blood Pressure Lowering Effects of Angiotensin-(1-7) in Primary Autonomic Failure

NCT02591173 | Terminated Early Phase 1 DMC

• 1 other identifier: 151461
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Pharmacologic approaches to increase levels or actions of the vasodilatory peptide angiotensin-(1-7) are currently in development for the treatment of hypertension based on findings from animal models. There are limited and contradictory clinical studies, however, and it is not clear if this peptide regulates blood pressure in humans. The purpose of this study is to better understand the cardiovascular effects angiotensin-(1-7) in human hypertension, and to examine interactions of this peptide with the autonomic nervous system. The investigators propose that the difficulties in showing angiotensin-(1-7) cardiovascular effects in previous clinical studies relates to the buffering capacity of the baroreceptor reflex to prevent changes in blood pressure. Autonomic failure provides the ideal patient population to test this hypothesis. These patients have loss of baroreflex buffering and have low levels of angiotensin-(1-7) in blood. The investigators will test if angiotensin-(1-7) infusion can lower blood pressure in patients with autonomic failure, and will determine the hemodynamic and hormonal mechanisms involved in this effect.

Conditions

Autonomic Nervous System Disorders; Pure Autonomic Failure; Shy-Drager Syndrome; Orthostatic Hypotension, Dysautonomic

Keywords

Autonomic; Hypertension; Renin-Angiotensin System

Outcome Measures

Primary Outcomes (1)

• Blood Pressure

  The decrease in blood pressure following angiotensin-(1-7) versus saline infusion.

  50 minutes

Secondary Outcomes (7)

• Heart Rate

  50 minutes

• Cardiac Output

  50 minutes

• Stroke Volume

  50 minutes

• Systemic Vascular Resistance

  50 minutes

• Renin Activity

  50 minutes

Study Arms (2)

Angiotensin-(1-7)

EXPERIMENTAL

Patients will receive an intravenous infusion of five ascending doses of Angiotensin-(1-7). The doses are: 1, 2, 4, 8 and 16 ng/kg/min. Each dose will be maintained for 10 minutes, for a total of 50 minutes.

Drug: Angiotensin-(1-7)

Saline

PLACEBO COMPARATOR

Patients will receive an intravenous infusion of saline that is matched in volume to the Angiotensin-(1-7) study day. The saline infusion will be maintained for 50 minutes.

Drug: Saline

Interventions

Angiotensin-(1-7) DRUG

This is a biologically active endogenous angiotensin peptide. It may play an important role in the regulation of blood pressure by dilating blood vessels.

Also known as: Angiotensin I (1-7), Angiotensin I/II (1-7) Acetate

Angiotensin-(1-7)

Saline DRUG

Normal saline will be used as the placebo comparator.

Also known as: normal saline, 0.9% sodium chloride

Saline

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females of all races between 18 to 80 years of age.
• Diagnosed with primary autonomic failure and supine hypertension. Supine hypertension will be defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 90 mmHg while lying down.
• Able and willing to provide informed consent.

You may not qualify if:

• Pregnancy or breast feeding.
• Hemoglobin \< 10.5 or hematocrit \< 32.
• High-risk patients (e.g. heart failure, symptomatic coronary artery disease, liver impairment, renal failure, history of stroke or myocardial infarction).
• Inability to give or withdraw informed consent.
• Other factors which in the investigator's opinion would prevent the patient from completing the protocol (e.g. clinically significant abnormalities on clinical, mental examination, or laboratory testing or inability to comply with the protocol).

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37211, United States

Location

MeSH Terms

Conditions

Autonomic Nervous System Diseases; Pure Autonomic Failure; Shy-Drager Syndrome; Hypertension

Interventions

angiotensin I (1-7); Acetates; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Nervous System Diseases; Primary Dysautonomias; Multiple System Atrophy; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Italo Biaggioni, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: October 29, 2015
• Study Start: February 1, 2016
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: January 12, 2021

Record last verified: 2021-01

Locations

US (1)