Treatment of Supine Hypertension in Autonomic Failure

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00223717
First received: September 14, 2005
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

Supine hypertension is a common problem that affects at least 50% of patients with primary autonomic failure. Supine hypertension can be severe, and complicates the treatment of orthostatic hypotension. Drugs used for the treatment of orthostatic hypotension (eg, fludrocortisone and pressor agents), worsen supine hypertension. High blood pressure may also cause target organ damage in this group of patients. The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure have not been defined.

In a study, we, the investigators at Vanderbilt University, examined 64 patients with AF, 29 with pure autonomic failure (PAF) and 35 with multiple system atrophy (MSA). 66% of patients had supine systolic (systolic blood pressure [SBP] > 150 mmHg) or diastolic (diastolic blood pressure [DBP] > 90 mmHg) hypertension (average blood pressure [BP]: 179 ± 5/89 ± 3 mmHg in 21 PAF and 175 ± 5/92 ± 3 mmHg in 21 MSA patients). Plasma norepinephrine (92 ± 15 pg/mL) and plasma renin activity (0.3 ± 0.05 ng/mL per hour) were very low in a subset of patients with AF and supine hypertension. (Shannon et al., 1997).

Our group has showed that a residual sympathetic function contributes to supine hypertension in patients with severe autonomic failure and that this effect is more prominent in patients with MSA than in those with PAF (Shannon et al., 2000). MSA patients had a marked depressor response to low infusion rates of trimethaphan, a ganglionic blocker; the response in PAF patients was more variable. At 1 mg/min, trimethaphan decreased supine SBP by 67 +/- 8 and 12 +/- 6 mmHg in MSA and PAF patients, respectively (P < 0.0001). MSA patients with supine hypertension also had greater SBP response to oral yohimbine, a central alpha2 receptor blocker, than PAF patients. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. This result suggests that residual sympathetic activity drives supine hypertension in MSA; in contrast, supine hypertension in PAF.

It is hoped that from this study will emerge a complete picture of the supine hypertension of autonomic failure. Understanding the mechanism of this paradoxical hypertension in the setting of profound loss of sympathetic function will improve our approach to the treatment of hypertension in autonomic failure, and it could also contribute to our understanding of hypertension in general.


Condition Intervention Phase
Hypertension
Drug: Clonidine
Drug: Nitroglycerin transdermal
Drug: Dipyridamole/ Aspirin (Aggrenox)
Drug: Desmopressin (DDAVP)
Drug: Sildenafil
Drug: Nifedipine
Drug: Hydralazine
Drug: Hydrochlorothiazide
Drug: Placebo
Drug: Bosentan
Drug: Diltiazem
Drug: Eplerenone
Drug: guanfacine
Dietary Supplement: L-arginine
Drug: captopril
Drug: carbidopa
Drug: losartan
Drug: metoprolol tartrate
Drug: nebivolol hydrochloride
Drug: prazosin hydrochloride
Drug: tamsulosin hydrochloride
Other: Head-up tilt.
Drug: aliskiren
Other: Local heat stress
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: The Pathophysiology and Treatment of Supine Hypertension in Patients With Autonomic Failure

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Decrease in supine systolic blood pressure [ Time Frame: 12 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Decrease in pressure natriuresis [ Time Frame: 12 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: June 2001
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1: Active drug or intervention
Clonidine, Nitroglycerin transdermal, Dipyridamole/ Aspirin (Aggrenox), Desmopressin (DDAVP), Sildenafil, Nifedipine, Hydralazine, Hydrochlorothiazide, Bosentan, Diltiazem, Eplerenone, guanfacine, L-arginine, captopril, carbidopa, losartan, metoprolol tartrate, nebivolol hydrochloride, prazosin hydrochloride, tamsulosin hydrochloride, Head-up tilt, aliskiren, local heat stress
Drug: Clonidine
0.1-0.2mg po. Single dose.
Other Name: Catapres
Drug: Nitroglycerin transdermal
0.05-0.2 mg patch. 1 application. Alone or in combination with DDAVP.
Other Name: Nitro-Dur
Drug: Dipyridamole/ Aspirin (Aggrenox)
dipyridamole 200 mg and aspirin 25 mg po. Single dose.
Other Name: Aggrenox
Drug: Desmopressin (DDAVP)
0.2 - 0.6mg po. Single dose. Alone or in combination with nitroglycerin transdermal or nifedipine
Other Name: DDAVP
Drug: Sildenafil
25- 100 mg po. Single dose.
Other Name: Viagra
Drug: Nifedipine
10-30 mg po. Single dose.
Other Name: Adalat
Drug: Hydralazine
10-50 mg po. Single dose
Drug: Hydrochlorothiazide
12.5-100 mg po. Single dose.
Other Name: Microzide
Drug: Bosentan
62.5 -125 mg po. Single dose.
Other Name: Tracleer
Drug: Diltiazem
30-60 mg po. Single dose.
Other Name: Cardizem
Drug: Eplerenone
50-100 mg po. Single dose.
Other Name: Inspra
Drug: guanfacine
1-3 mg po. Single dose.
Other Name: Tenex
Dietary Supplement: L-arginine
6-17 g po. Single dose
Drug: captopril
25-50 mg PO. Single dose.
Other Name: capoten
Drug: carbidopa
25-200 mg PO. Single dose.
Other Name: Lodosyn
Drug: losartan
25-200 mg PO. Single dose.
Other Name: cozaar
Drug: metoprolol tartrate
25-100 mg PO. Single dose.
Other Name: lopressor
Drug: nebivolol hydrochloride
2.5-40 mg PO. Single dose.
Other Name: Bystolic
Drug: prazosin hydrochloride
0.5-1 mg PO. Single dose.
Other Name: Minipress
Drug: tamsulosin hydrochloride
0.4-0.8 mg PO. Single dose.
Other Name: Flomax
Other: Head-up tilt.
Head of the bed elevated 10 degrees (7 inch) or whole bed tilted head-up 5 degrees in reverse trendelenburg (head of the bed elevated 7 inches)
Other Name: HUT
Drug: aliskiren
aliskiren (Tekturna) 150-300mg po single dose
Other Name: Tekturna
Other: Local heat stress
Passive heat-stress using a commercial heating pad applied over the abdomen and part of the torso
Other Name: heating pad
Placebo Comparator: 2: Placebo
placebo pill or patch
Drug: Placebo
Po or patch. Single dose.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with autonomic failure and with supine hypertension from all races

Exclusion Criteria:

  • All medical students
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00223717

Contacts
Contact: Bonnie Black, RN adcresearch@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Bonnie Black, RN       adcresearch@vanderbilt.edu   
Principal Investigator: Italo Biaggioni, MD         
Sub-Investigator: David Robertson, MD         
Sub-Investigator: Satish Raj, MD         
Sub-Investigator: Alfredo Gamboa, MD         
Sub-Investigator: Cyndya Shibao, MD         
Sub-Investigator: Andre Diedrich, MD         
Sub-Investigator: Luis E Okamoto, MD         
Sub-Investigator: Amy C Arnold, PhD         
Sub-Investigator: Cindy A Dorminy, MEd, LPN         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Italo Biaggioni, MD Vanderbilt University
  More Information

Additional Information:
Publications:

Responsible Party: Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00223717     History of Changes
Other Study ID Numbers: 010189
Study First Received: September 14, 2005
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
Supine Hypertension
Hypertension
Treatment
Autonomic failure
Pure autonomic failure
Multiple System Atrophy
Shy-Drager Syndrome

Additional relevant MeSH terms:
Autonomic Nervous System Diseases
Nervous System Diseases
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Hypertension
Pure Autonomic Failure
Vascular Diseases
Cardiovascular Diseases
Primary Dysautonomias
Clonidine
Aspirin
Nebivolol
Metoprolol
Hydrochlorothiazide
Captopril
Prazosin
Hydralazine
Guanfacine
Diltiazem
Metoprolol succinate
Tamsulosin
Nifedipine
Sildenafil
Dipyridamole
Nitroglycerin
Carbidopa
Eplerenone
Deamino Arginine Vasopressin
Aspirin, dipyridamole drug combination

ClinicalTrials.gov processed this record on September 30, 2014