Autonomic Nervous System DisordersEarly Phase 1NCT02591173
Blood Pressure Lowering Effects of Angiotensin-(1-7) in Primary Autonomic Failure
A Early Phase 1 study testing Angiotensin-(1-7) and Saline in people with Autonomic Nervous System Disorders and Pure Autonomic Failure, run by Vanderbilt University Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Autonomic Nervous System Disorders, Pure Autonomic Failure, Shy-Drager Syndrome
- What is being tested?
- Angiotensin-(1-7) and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to Jul 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37211
About this study
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.
Read the detailed 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.
- Conditions
- Autonomic Nervous System Disorders, Pure Autonomic Failure, Shy-Drager Syndrome, Orthostatic Hypotension, Dysautonomic
- Being tested
- Angiotensin-(1-7), Saline
- Keywords
- Autonomic, Hypertension, Renin-Angiotensin System
- Medical subject headings
- Autonomic Nervous System Diseases, Pure Autonomic Failure, Shy-Drager Syndrome, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin-(1-7)Drug
Also called Angiotensin I (1-7), Angiotensin I/II (1-7) Acetate
This is a biologically active endogenous angiotensin peptide. It may play an important role in the regulation of blood pressure by dilating blood vessels.
SalineDrug
Also called normal saline, 0.9% sodium chloride
Normal saline will be used as the placebo comparator.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Pressure
The decrease in blood pressure following angiotensin-(1-7) versus saline infusion.
Measured: 50 minutes
Secondary outcomes (7)
Heart Rate
The change in heart rate following angiotensin-(1-7) versus saline infusion.
Measured: 50 minutes
Cardiac Output
The change in cardiac output following angiotensin-(1-7) versus saline infusion.
Measured: 50 minutes
Stroke Volume
The change in stroke volume following angiotensin-(1-7) versus saline infusion.
Measured: 50 minutes
Systemic Vascular Resistance
The change in systemic vascular resistance following angiotensin-(1-7) versus saline infusion.
Measured: 50 minutes
Renin Activity
The change in plasma renin activity following angiotensin-(1-7) versus placebo infusion.
Measured: 50 minutes
Angiotensin Peptides
The change in plasma angiotensin peptides following angiotensin-(1-7) versus placebo infusion.
Measured: 50 minutes
Aldosterone
The change in plasma aldosterone following angiotensin-(1-7) versus placebo infusion.
Measured: 50 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2015 (estimated)
- Study startFeb 2016
- Primary completionJul 2020
- Study completionJul 2020
Why it stopped: Difficulty recruiting
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autonomic Nervous System DisordersStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Italo Biaggioni, Vanderbilt University Medical Center
- Investigators
- Italo Biaggioni, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02591173
- Sponsor's protocol ID
- 151461
- Status last verified
- Jan 2021
- First submitted
- 27 Oct 2015
- Last updated
- 12 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood Pressure Lowering Effects of Angiotensin-(1-7) in Primary Autonomic Failure
- ClinicalTrials.gov ID
- NCT02591173
- Acronym / sponsor ID
- 151461
- Conditions
- Autonomic Nervous System Disorders, Pure Autonomic Failure, Shy-Drager Syndrome, Orthostatic Hypotension, Dysautonomic
- Keywords
- Autonomic, Hypertension, Renin-Angiotensin System
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty recruiting
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Feb 2016 (actual)
- Primary completion
- Jul 2020 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 29 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Angiotensin-(1-7) | Experimental | Drug: Angiotensin-(1-7)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. |
| Saline | Placebo comparator | Drug: SalinePatients 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiotensin-(1-7)Also: Angiotensin I (1-7), Angiotensin I/II (1-7) AcetateThis is a biologically active endogenous angiotensin peptide. It may play an important role in the regulation of blood pressure by dilating blood vessels. | Drug | Angiotensin-(1-7) |
| SalineAlso: normal saline, 0.9% sodium chlorideNormal saline will be used as the placebo comparator. | Drug | Saline |
Primary outcome
Blood Pressure
Time frame: 50 minutes
The decrease in blood pressure following angiotensin-(1-7) versus saline infusion.
7 secondary outcomes
Heart Rate
Time frame: 50 minutes
Cardiac Output
Time frame: 50 minutes
Stroke Volume
Time frame: 50 minutes
Systemic Vascular Resistance
Time frame: 50 minutes
Renin Activity
Time frame: 50 minutes
Angiotensin Peptides
Time frame: 50 minutes
Aldosterone
Time frame: 50 minutes
Results and safety
The study was stopped early (reason given: Difficulty recruiting). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Italo Biaggioni, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Angiotensin-(1-7) and Saline in people with Autonomic Nervous System Disorders and Pure Autonomic Failure, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulty recruiting). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Pressure (time frame: 50 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2021.