The Role of Endothelin in the Supine Hypertension of Autonomic Failure
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01119417|
Recruitment Status : Enrolling by invitation
First Posted : May 7, 2010
Last Update Posted : January 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Hypertension Pure Autonomic Failure Multiple System Atrophy||Drug: BQ123 Drug: Bq123 Drug: Saline||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||The Role of Endothelin in the Supine Hypertension of Autonomic Failure|
|Study Start Date :||May 2010|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2020|
Low dose day: 25 nmol/min, single IV infusion for 15 min.
Other Name: BQ-123 sodium saltDrug: BQ123
Low dose day: 50 nmol/min, single IV infusion for 15 min
Other Name: BQ-123 sodium saltDrug: Bq123
High dose day: 100 nmol/min, single IV infusion for 15 min.
Other Name: BQ-123 sodium saltDrug: BQ123
High dose day: 300 nmol/min, single IV infusion for 15 min.
Other Name: BQ-123 sodium salt
Placebo Comparator: Saline
2-3 IV saline infusions for 15 min each.
Other Name: Normal saline, 0.9% sodium chloride
- Change in Systolic BP [ Time Frame: 0 -4 hr post infusion ]
- Change in cardiac output, stroke volume and systemic vascular resistance [ Time Frame: 0-4 hr post infusion ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01119417
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Italo Biaggioni, M.D.||Vanderbilt University|