Treatment of Supine Hypertension in Autonomic Failure
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|ClinicalTrials.gov Identifier: NCT00223717|
Recruitment Status : Completed
First Posted : September 22, 2005
Last Update Posted : October 13, 2017
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 or disease||Intervention/treatment||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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||152 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||The Pathophysiology and Treatment of Supine Hypertension in Patients With Autonomic Failure|
|Study Start Date :||January 2001|
|Actual Primary Completion Date :||January 2017|
|Actual Study Completion Date :||January 2017|
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
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
25- 100 mg po. Single dose.
Other Name: Viagra
10-30 mg po. Single dose.
Other Name: Adalat
10-50 mg po. Single dose
12.5-100 mg po. Single dose.
Other Name: Microzide
62.5 -125 mg po. Single dose.
Other Name: Tracleer
30-60 mg po. Single dose.
Other Name: Cardizem
50-100 mg po. Single dose.
Other Name: Inspra
1-3 mg po. Single dose.
Other Name: Tenex
Dietary Supplement: L-arginine
6-17 g po. Single dose
25-50 mg PO. Single dose.
Other Name: capoten
25-200 mg PO. Single dose.
Other Name: Lodosyn
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
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
Po or patch. Single dose.
- Decrease in supine systolic blood pressure [ Time Frame: 12 hours ]
- Decrease in pressure natriuresis [ Time Frame: 12 hours ]
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): NCT00223717
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Italo Biaggioni, MD||Vanderbilt University|