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

Pure Autonomic Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02591173
• Other study ID #: 151461
• Status: Terminated
• Phase: Early Phase 1
• Start date: February 2016
• Est. completion date: July 2020

Study information

• Verified date: January 2021
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is an inpatient study that requires at least four days of admission to the Vanderbilt Clinical Research Center. Autonomic failure patients will be placed on a fixed diet during the admission and will have routine tests performed for screening and clinical characterization. Patients will then receive intravenous angiotensin-(1-7) or saline infusion on two separate study days, with each study day lasting approximately 3 hours. There will be at least one washout day between study days. Patients will be instrumented with two intravenous catheters (one for blood sampling and one for drug infusion), arm and finger blood pressure cuffs, and sticky patches to measure heart rate during the study. The investigators will take baseline measurements of blood pressure and heart rate and collect blood samples. The investigators will also perform a rebreathing test to measure the heart's pumping capacity. After baseline measurements, the investigators will infusion angiotensin-(1-7) or saline for 50 minutes. There will be five doses of angiotensin-(1-7). Each dose will be maintained for 10 minutes. The investigators will measure blood pressure and heart rate, repeat the rebreathing test, and collect blood samples at the end of each dosing period.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: July 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Related Conditions & MeSH terms

• Autonomic Nervous System Diseases
• Autonomic Nervous System Disorders
• Hypotension
• Hypotension, Orthostatic
• Multiple System Atrophy
• Nervous System Diseases
• Orthostatic Hypotension, Dysautonomic
• Primary Dysautonomias
• Pure Autonomic Failure
• Shy-Drager Syndrome

Intervention

Drug:
• Angiotensin-(1-7)
This is a biologically active endogenous angiotensin peptide. It may play an important role in the regulation of blood pressure by dilating blood vessels.
• Saline
Normal saline will be used as the placebo comparator.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Pressure	The decrease in blood pressure following angiotensin-(1-7) versus saline infusion.	50 minutes
Secondary	Heart Rate	The change in heart rate following angiotensin-(1-7) versus saline infusion.	50 minutes
Secondary	Cardiac Output	The change in cardiac output following angiotensin-(1-7) versus saline infusion.	50 minutes
Secondary	Stroke Volume	The change in stroke volume following angiotensin-(1-7) versus saline infusion.	50 minutes
Secondary	Systemic Vascular Resistance	The change in systemic vascular resistance following angiotensin-(1-7) versus saline infusion.	50 minutes
Secondary	Renin Activity	The change in plasma renin activity following angiotensin-(1-7) versus placebo infusion.	50 minutes
Secondary	Angiotensin Peptides	The change in plasma angiotensin peptides following angiotensin-(1-7) versus placebo infusion.	50 minutes
Secondary	Aldosterone	The change in plasma aldosterone following angiotensin-(1-7) versus placebo infusion.	50 minutes