HypertensionPhase 1NCT01119417
The Role of Endothelin in the Supine Hypertension of Autonomic Failure
A Phase 1 study testing BQ123 and Saline 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 endothelin plays a role in the pathogenesis of supine hypertension in pure autonomic failure by increasing vascular resistance. 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?
- BQ123 and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to May 2021
- 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 and supine hypertension from all races, who are in the hospital participating in the study "The Evaluation and Treatment of Autonomic Failure" (IRB# 000814).
- Supine hypertension, defined as a systolic blood pressure >150 mm Hg or diastolic blood pressure > 90 mm Hg.
- Males and females, between 18-85yr.
- Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care.
Who cannot join
- Pregnant women.
- High-risk patients (e.g. heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction).
- History of serious allergies or asthma.
- In the investigator's opinion, have clinically significant abnormalities on clinical, mental examination or laboratory testing.
- All medical students.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to test the hypothesis that endothelin plays a role in the pathogenesis of supine hypertension in pure autonomic failure by increasing vascular resistance. To gauge its contribution to blood pressure regulation, pure autonomic failure and multiple system atrophy patients with supine hypertension will undergo a medication testing with the endothelin blocker, BQ123. We will compare the hemodynamic effects between PAF and MSA patients. Our primary endpoint will be the decrease in blood pressure during the administration of this compound.
Read the detailed description
The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure are not completely understood.In MSA patients, supine hypertension may be explained by residual sympathetic tone, possibly acting on hypersensitive adrenoreceptors and unstrained by the lack of baroreflex modulation. In contrast, the pathogenesis of hypertension in PAF remains unknown. Hypertension in these patients is not related to intravascular volume, residual sympathetic tone, or renin mechanisms. Increased vascular resistance is the underlying hemodynamic mechanism. The driving force of this increased vascular tone, however, is not known.
We hypothesize that endothelin (ET)-l contributes to the increased vascular resistance in pure autonomic failure patients with supine hypertension. To gauge its contribution to blood pressure regulation, we will induce endothelin blockade with acute systemic administration of BQ123 in an ascending dose regimen (25, 50, 100 and 300 nmol/min) and we will compare the hemodynamic effects between PAF and MSA patients.
Subjects will be studied on 3 different days, one with saline (placebo) and two with BQ123: a 'low dose' day (25 and 50 nmol/min infusions separated by 75 min) and a 'high dose' day (100 and 300 nmol/min infusions separated by 75 min). The order of the placebo day will be randomized in a single-blinded manner so that each subject receives it on a different visit. The order of the BQ123 study days will be always the same, starting with the low dose. If SBP drops by >40 mm Hg or SBP < 130 mm Hg during the monitoring period after the first or second infusion, the following dose(s) of BQ123 will not be given and patients will receive normal saline until the study ends.
Ganglionic Blockade with Trimethaphan (optional study day):
The purpose of this study day is to determine the level of residual sympathetic tone that contributes to supine hypertension in each autonomic failure patient by inducing transient withdrawal of the autonomic nervous system. This approach would allow us to identify patients in whom supine hypertension is not driven by sympathetic tone and thus, better characterize the role of endothelin in the hypertension of these patients.
- Being tested
- BQ123, Saline
- Keywords
- supine Hypertension, autonomic failure, BQ123, BQ-123, endothelin
- 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.
BQ123Drug
Also called BQ-123 sodium salt
Low dose day: 25 nmol/min, single IV infusion for 15 min.
BQ123Drug
Also called BQ-123 sodium salt
Low dose day: 50 nmol/min, single IV infusion for 15 min
Bq123Drug
Also called BQ-123 sodium salt
High dose day: 100 nmol/min, single IV infusion for 15 min.
BQ123Drug
Also called BQ-123 sodium salt
High dose day: 300 nmol/min, single IV infusion for 15 min.
SalineDrug
Also called Normal saline, 0.9% sodium chloride
2-3 IV saline infusions for 15 min each.
| Study group | Role | What they receive |
|---|---|---|
| BQ123 | Experimental | endothelin blocker Receives: Drug: BQ123 |
| Saline | Placebo comparator | IV saline Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Systolic BP
Change from baseline in systolic blood pressure
Measured: 0 -4 hr post infusion
Secondary outcomes (1)
Change in cardiac output, stroke volume and systemic vascular resistance
Percent change from baseline in hemodynamic parameters
Measured: 0-4 hr post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2010 (estimated)
- Study startMay 2010
- Primary completionMay 2021
- Study completionMay 2021
Why it stopped: No participants were enrolled
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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 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, M.D., Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01119417
- Sponsor's protocol ID
- 091344
- Status last verified
- Sep 2021
- First submitted
- 4 May 2010
- Last updated
- 5 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Endothelin in the Supine Hypertension of Autonomic Failure
- ClinicalTrials.gov ID
- NCT01119417
- Acronym / sponsor ID
- 091344
- Keywords
- supine Hypertension, autonomic failure, BQ123, BQ-123, endothelin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants were enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- May 2010 (actual)
- Primary completion
- May 2021 (actual)
- Study completion
- May 2021 (actual)
- First posted
- 7 May 2010 (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 endothelin plays a role in the pathogenesis of supine hypertension in pure autonomic failure by increasing vascular resistance. To gauge its contribution to blood pressure regulation, pure autonomic failure and multiple system atrophy patients with supine hypertension will undergo a medication testing with the endothelin blocker, BQ123. We will compare the hemodynamic effects between PAF and MSA patients. Our primary endpoint will be the decrease in blood pressure during the administration of this compound.
Detailed description
The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure are not completely understood.In MSA patients, supine hypertension may be explained by residual sympathetic tone, possibly acting on hypersensitive adrenoreceptors and unstrained by the lack of baroreflex modulation. In contrast, the pathogenesis of hypertension in PAF remains unknown. Hypertension in these patients is not related to intravascular volume, residual sympathetic tone, or renin mechanisms. Increased vascular resistance is the underlying hemodynamic mechanism. The driving force of this increased vascular tone, however, is not known.
We hypothesize that endothelin (ET)-l contributes to the increased vascular resistance in pure autonomic failure patients with supine hypertension. To gauge its contribution to blood pressure regulation, we will induce endothelin blockade with acute systemic administration of BQ123 in an ascending dose regimen (25, 50, 100 and 300 nmol/min) and we will compare the hemodynamic effects between PAF and MSA patients.
Subjects will be studied on 3 different days, one with saline (placebo) and two with BQ123: a 'low dose' day (25 and 50 nmol/min infusions separated by 75 min) and a 'high dose' day (100 and 300 nmol/min infusions separated by 75 min). The order of the placebo day will be randomized in a single-blinded manner so that each subject receives it on a different visit. The order of the BQ123 study days will be always the same, starting with the low dose. If SBP drops by >40 mm Hg or SBP < 130 mm Hg during the monitoring period after the first or second infusion, the following dose(s) of BQ123 will not be given and patients will receive normal saline until the study ends.
Ganglionic Blockade with Trimethaphan (optional study day):
The purpose of this study day is to determine the level of residual sympathetic tone that contributes to supine hypertension in each autonomic failure patient by inducing transient withdrawal of the autonomic nervous system. This approach would allow us to identify patients in whom supine hypertension is not driven by sympathetic tone and thus, better characterize the role of endothelin in the hypertension of these patients.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BQ123 | Experimental | Drug: BQ123endothelin blocker |
| Saline | Placebo comparator | Drug: SalineIV saline |
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 and supine hypertension from all races, who are in the hospital participating in the study "The Evaluation and Treatment of Autonomic Failure" (IRB# 000814).
- Supine hypertension, defined as a systolic blood pressure >150 mm Hg or diastolic blood pressure > 90 mm Hg.
- Males and females, between 18-85yr.
- Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care.
Key exclusion criteria (5 listed)
- Pregnant women.
- High-risk patients (e.g. heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction).
- History of serious allergies or asthma.
- In the investigator's opinion, have clinically significant abnormalities on clinical, mental examination or laboratory testing.
- All medical students.
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 |
|---|---|---|
| BQ123Also: BQ-123 sodium saltLow dose day: 25 nmol/min, single IV infusion for 15 min. | Drug | BQ123 |
| BQ123Also: BQ-123 sodium saltLow dose day: 50 nmol/min, single IV infusion for 15 min | Drug | BQ123 |
| Bq123Also: BQ-123 sodium saltHigh dose day: 100 nmol/min, single IV infusion for 15 min. | Drug | BQ123 |
| BQ123Also: BQ-123 sodium saltHigh dose day: 300 nmol/min, single IV infusion for 15 min. | Drug | BQ123 |
| SalineAlso: Normal saline, 0.9% sodium chloride2-3 IV saline infusions for 15 min each. | Drug | Saline |
Primary outcome
Change in Systolic BP
Time frame: 0 -4 hr post infusion
Change from baseline in systolic blood pressure
1 secondary outcome
Change in cardiac output, stroke volume and systemic vascular resistance
Time frame: 0-4 hr post infusion
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2021.
- Individual participant dataSharing planned: No
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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, M.D. 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 BQ123 and Saline 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 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: withdrawn, as of the sponsor's last update on 5 Oct 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?
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 withdrawn before enrolling participants, so there are no results.
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?
Change in Systolic BP (time frame: 0 -4 hr post infusion). 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 5 Oct 2021.