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

• Status: Terminated
• Trial end date: 2020-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University; Vanderbilt University Medical Center
• Treatments: Angiotensin I (1-7); Angiotensin II; Angiotensinogen

Criteria

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).