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| Sponsor: | Vanderbilt University |
|---|---|
| Information provided by: | Vanderbilt University |
| ClinicalTrials.gov Identifier: | NCT00223717 |
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. |
Phase I Phase II |
| 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 |
| Estimated Enrollment: | 160 |
| Study Start Date: | June 2001 |
| Estimated Study Completion Date: | October 2012 |
| Estimated Primary Completion Date: | October 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 1: Active drug or intervention |
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
|
| Placebo Comparator: 2: Placebo |
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 |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: Bonnie Black, RN | adcresearch@vanderbilt.edu |
| 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 | |
| Principal Investigator: | Italo Biaggioni, MD | Vanderbilt University |
More Information
| Responsible Party: | Italo Biaggioni, Vanderbilt University |
| ClinicalTrials.gov Identifier: | NCT00223717 History of Changes |
| Other Study ID Numbers: | 010189 |
| Study First Received: | September 14, 2005 |
| Last Updated: | March 15, 2011 |
| Health Authority: | United States: Food and Drug Administration |
|
Supine Hypertension Hypertension Treatment Autonomic failure |
Pure autonomic failure Multiple System Atrophy Shy-Drager Syndrome |
|
Hypertension Pure Autonomic Failure Vascular Diseases Cardiovascular Diseases Primary Dysautonomias Autonomic Nervous System Diseases Nervous System Diseases Aspirin Aspirin, dipyridamole drug combination Dipyridamole Clonidine Metoprolol Captopril Diltiazem Nitroglycerin |
Hydralazine Hydrochlorothiazide Nifedipine Prazosin Nebivolol Guanfacine Losartan Bosentan Sildenafil Carbidopa Deamino Arginine Vasopressin Metoprolol succinate Tamsulosin Eplerenone Anti-Inflammatory Agents, Non-Steroidal |
