Blood Pressure Lowering Effects of Angiotensin-(1-7) in Primary Autonomic Failure
| Status: | Recruiting |
|---|---|
| Conditions: | Other Indications, Cardiology, Cardiology, Neurology, Neurology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Neurology, Other |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 7/28/2018 |
| Start Date: | February 2016 |
| End Date: | December 2019 |
| Contact: | Bonnie K Black, RN |
| Email: | adcresearch@vanderbilt.edu |
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.
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.
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.
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.
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).
We found this trial at
1
site
2201 West End Ave
Nashville, Tennessee 37232
Nashville, Tennessee 37232
(615) 322-7311
Principal Investigator: Amy C Arnold, Ph.D.
Vanderbilt University Vanderbilt offers undergraduate programs in the liberal arts and sciences, engineering, music, education...
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