HypertensionPhase 1NCT01292694
Contribution of Angiotensin II to Supine Hypertension in Autonomic Failure
A Phase 1 study testing Losartan and Captopril in people with Hypertension and Pure Autonomic Failure, run by Vanderbilt University at 1 site in United States.
Trial summary
The purpose of this study is to test the hypothesis that angiotensin II plays a role in the supine hypertension of primary autonomic failure. To determine the contribution of angiotensin II to renin and blood pressure regulation in autonomic failure, patients with multiple system atrophy [MSA] or pure autonomic… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hypertension, Pure Autonomic Failure, Multiple System Atrophy
- What is being tested?
- Losartan and Captopril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Mar 2017
- Phase
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with autonomic failure who exhibit supine hypertension and are in the hospital already participating in the study "The Evaluation and Treatment of Autonomic Failure [IRB # 000814]
- Supine hypertension, defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mm Hg
- Males and females of all races, between 18 to 85 years of age
- Able and willing to provide informed consent with the understanding that they may withdraw consent at any time without prejudice to future medical care
Who cannot join
- All medical students
- Pregnant women
- Patients with a history of angioedema
- Patients with a known allergy to any ACE inhibitor or angiotensin receptor blocker
- High-risk patients [e.g. heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction]
- Patients with hemoglobin < 10.5 [or hematocrit < 32]
- Inability to give, or withdraw, informed consent
- Other factors which in the investigator's opinion would prevent the patient from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to test the hypothesis that angiotensin II plays a role in the supine hypertension of primary autonomic failure. To determine the contribution of angiotensin II to renin and blood pressure regulation in autonomic failure, patients with multiple system atrophy [MSA] or pure autonomic failure [PAF] and supine hypertension will undergo medication testing with the angiotensin II receptor blocker losartan. The investigators will compare the biochemical and hemodynamic effects between MSA and PAF patients. In a subset of patients, the investigators will also give the ACE inhibitor captopril. Our primary endpoint will be changes in plasma renin activity, and subsequent components of the circulating renin-angiotensin system, in response to angiotensin II blockade. Our secondary outcome will be changes in hemodynamic measures during administration of these drugs.
Read the detailed description
Primary autonomic failure is a disabling condition characterized by orthostatic hypotension. It is less well appreciated that at least 50% of these patients have high blood pressure when lying down [supine hypertension]. The mechanisms underlying supine hypertension in autonomic failure remain poorly understood. The hypertension in MSA patients may be explained by residual sympathetic tone, possibly acting on hypersensitive adrenoreceptors and unrestrained by the lack of baroreflex modulation. In contrast, the hypertension in PAF is associated with increased vascular resistance in the absence of residual sympathetic tone. However, the factors driving an elevation in either sympathetic or vascular tone in these patients remain unclear.
The investigators hypothesize that angiotensin II, a hormone widely implicated in blood pressure regulation, plays a role in the supine hypertension of autonomic failure. To determine the contribution of angiotensin II to renin and blood pressure regulation in autonomic failure, the investigators will administer the angiotensin II receptor blocker losartan to MSA and PAF patients with supine hypertension. The primary endpoint will be changes in plasma renin activity, and subsequent components of the circulating renin-angiotensin system, in response to angiotensin II blockade. The secondary outcomes will be the decrease in blood pressure and changes in heart rate, cardiac output, stroke volume and systemic vascular resistance during administration of these drugs.
Subjects will be studied on 2 separate days, one with oral administration of placebo and the other with losartan [50 mg]. The order of administration will be randomized in a single-blind manner. The investigators will collect blood samples before and every 2 hours after administration for up to 6 hours to determine if angiotensin II regulates plasma renin activity, and other components of the circulating renin-angiotensin system, in autonomic failure. The investigators will also obtain hemodynamic measurements before and every 1 hour (blood pressure and heart rate) or 2 hours (cardiac output, stroke volume and systemic vascular resistance) after drug administration.
In a subset of patients the investigators will also administer the ACE inhibitor captopril [50 mg] on a separate study day using the same methods. Captopril is less specific for assessing the role of angiotensin II to hypertension. However, it may provide important information on the mechanism for angiotensin II formation in these patients.
- Being tested
- Losartan, Captopril, Placebo
- Keywords
- supine hypertension, autonomic failure, angiotensin, losartan, captopril
- Medical subject headings
- Hypertension, Pure Autonomic Failure, Multiple System Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Cozaar
Oral, single-dose, 50 mg tablet
CaptoprilDrug
Also called Capoten
Oral, single-dose, 50 mg tablet
PlaceboDrug
Oral, single administration, gelatin capsule filled with microcrystalline cellulose
| Study group | Role | What they receive |
|---|---|---|
| Losartan | Experimental | Angiotensin II AT1 receptor antagonist which blocks the actions of angiotensin II Receives: Drug: Losartan |
| Captopril | Experimental | ACE inhibitor which blocks the formation of angiotensin II Receives: Drug: Captopril |
| Placebo Tablet | Placebo comparator | A placebo tablet will be provided by the Vanderbilt Investigational Drug Service for these studies. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in plasma renin activity and subsequent components of the circulating renin-angiotensin system
Changes in supine plasma renin activity and aldosterone following drug administration
Measured: 0 - 6 hours post administration
Secondary outcomes (2)
Changes in blood pressure
Changes in supine blood pressure following drug administration
Measured: 0 - 6 hours post administration
Changes in heart rate, cardiac output, stroke volume and systemic vascular resistance
Changes in supine systemic hemodynamics following drug administration
Measured: 0 - 6 hours post administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2011 (estimated)
- Study startMar 2011
- Primary completionMar 2017
- Study completionMar 2017
Why it stopped: Could not enroll enough participants, and lost funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- 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
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Italo Biaggioni, Vanderbilt University
- Investigators
- Italo Biaggioni, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01292694
- Sponsor's protocol ID
- 101618
- Status last verified
- Aug 2018
- First submitted
- 8 Feb 2011
- Last updated
- 24 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contribution of Angiotensin II to Supine Hypertension in Autonomic Failure
- ClinicalTrials.gov ID
- NCT01292694
- Acronym / sponsor ID
- 101618
- Keywords
- supine hypertension, autonomic failure, angiotensin, losartan, captopril
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Could not enroll enough participants, and lost funding.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Mar 2011 (actual)
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 9 Feb 2011 (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.
The purpose of this study is to test the hypothesis that angiotensin II plays a role in the supine hypertension of primary autonomic failure. To determine the contribution of angiotensin II to renin and blood pressure regulation in autonomic failure, patients with multiple system atrophy [MSA] or pure autonomic failure [PAF] and supine hypertension will undergo medication testing with the angiotensin II receptor blocker losartan. The investigators will compare the biochemical and hemodynamic effects between MSA and PAF patients. In a subset of patients, the investigators will also give the ACE inhibitor captopril. Our primary endpoint will be changes in plasma renin activity, and subsequent components of the circulating renin-angiotensin system, in response to angiotensin II blockade. Our secondary outcome will be changes in hemodynamic measures during administration of these drugs.
Detailed description
Primary autonomic failure is a disabling condition characterized by orthostatic hypotension. It is less well appreciated that at least 50% of these patients have high blood pressure when lying down [supine hypertension]. The mechanisms underlying supine hypertension in autonomic failure remain poorly understood. The hypertension in MSA patients may be explained by residual sympathetic tone, possibly acting on hypersensitive adrenoreceptors and unrestrained by the lack of baroreflex modulation. In contrast, the hypertension in PAF is associated with increased vascular resistance in the absence of residual sympathetic tone. However, the factors driving an elevation in either sympathetic or vascular tone in these patients remain unclear.
The investigators hypothesize that angiotensin II, a hormone widely implicated in blood pressure regulation, plays a role in the supine hypertension of autonomic failure. To determine the contribution of angiotensin II to renin and blood pressure regulation in autonomic failure, the investigators will administer the angiotensin II receptor blocker losartan to MSA and PAF patients with supine hypertension. The primary endpoint will be changes in plasma renin activity, and subsequent components of the circulating renin-angiotensin system, in response to angiotensin II blockade. The secondary outcomes will be the decrease in blood pressure and changes in heart rate, cardiac output, stroke volume and systemic vascular resistance during administration of these drugs.
Subjects will be studied on 2 separate days, one with oral administration of placebo and the other with losartan [50 mg]. The order of administration will be randomized in a single-blind manner. The investigators will collect blood samples before and every 2 hours after administration for up to 6 hours to determine if angiotensin II regulates plasma renin activity, and other components of the circulating renin-angiotensin system, in autonomic failure. The investigators will also obtain hemodynamic measurements before and every 1 hour (blood pressure and heart rate) or 2 hours (cardiac output, stroke volume and systemic vascular resistance) after drug administration.
In a subset of patients the investigators will also administer the ACE inhibitor captopril [50 mg] on a separate study day using the same methods. Captopril is less specific for assessing the role of angiotensin II to hypertension. However, it may provide important information on the mechanism for angiotensin II formation in these patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Losartan | Experimental | Drug: LosartanAngiotensin II AT1 receptor antagonist which blocks the actions of angiotensin II |
| Captopril | Experimental | Drug: CaptoprilACE inhibitor which blocks the formation of angiotensin II |
| Placebo Tablet | Placebo comparator | Drug: PlaceboA placebo tablet will be provided by the Vanderbilt Investigational Drug Service for these studies. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with autonomic failure who exhibit supine hypertension and are in the hospital already participating in the study "The Evaluation and Treatment of Autonomic Failure [IRB # 000814]
- Supine hypertension, defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mm Hg
- Males and females of all races, between 18 to 85 years of age
- Able and willing to provide informed consent with the understanding that they may withdraw consent at any time without prejudice to future medical care
Key exclusion criteria (8 listed)
- All medical students
- Pregnant women
- Patients with a history of angioedema
- Patients with a known allergy to any ACE inhibitor or angiotensin receptor blocker
- High-risk patients [e.g. heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction]
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 |
|---|---|---|
| LosartanAlso: CozaarOral, single-dose, 50 mg tablet | Drug | Losartan |
| CaptoprilAlso: CapotenOral, single-dose, 50 mg tablet | Drug | Captopril |
| PlaceboOral, single administration, gelatin capsule filled with microcrystalline cellulose | Drug | Placebo Tablet |
Primary outcome
Changes in plasma renin activity and subsequent components of the circulating renin-angiotensin system
Time frame: 0 - 6 hours post administration
Changes in supine plasma renin activity and aldosterone following drug administration
2 secondary outcomes
Changes in blood pressure
Time frame: 0 - 6 hours post administration
Changes in heart rate, cardiac output, stroke volume and systemic vascular resistance
Time frame: 0 - 6 hours post administration
Results and safety
The study was stopped early (reason given: Could not enroll enough participants, and lost funding.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2018.
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Losartan and Captopril in people with Hypertension and Pure Autonomic Failure, run by Vanderbilt University 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 4 inclusion and 8 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 24 Aug 2018. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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: Could not enroll enough participants, and lost funding.). 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?
Changes in plasma renin activity and subsequent components of the circulating renin-angiotensin system (time frame: 0 - 6 hours post administration). 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 24 Aug 2018.