Treatment of Orthostatic Hypotension in Autonomic Failure - Full Text View

Sponsor:	Vanderbilt University
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00223691

Purpose

The autonomic nervous system serves multiple regulatory functions in the body, including the regulation of blood pressure and heart rate, gut motility, sweating and sexual function. There are several diseases characterized by abnormal function of the autonomic nervous system. Medications can also alter autonomic function. Impairment of the autonomic nervous system by diseases or drugs may lead to several symptoms, including blood pressure problems (e.g., high blood pressure lying down and low blood pressure on standing), sweating abnormalities, constipation or diarrhea and sexual dysfunction. Because treatment options for these patients are limited. We propose to study patients autonomic failure and low blood pressure upon standing and determine the cause of their disease by history and examination and their response to autonomic testing which have already been standardized in our laboratory. Based on their possible cause, we will tests different medications that may alleviate their symptoms.

Condition	Intervention	Phase
Autonomic Failure Orthostatic Hypotension	Drug: Atomoxetine Drug: Acarbose Drug: Pyridostigmine Bromide Drug: Yohimbine Drug: Midodrine HCl Drug: placebo Drug: Modafinil Drug: Octreotide Other: water intake Drug: Diphenhydramine Hydrochloride Drug: Ranitidine HCL Drug: Tranylcypromine Drug: Ergotamine/ Caffeine Drug: Celecoxib Drug: Pseudoephedrine Drug: Methylphenidate Drug: Indomethacin Drug: Ibuprofen Drug: Oxymetazoline 0.05% nasal solution Dietary Supplement: Bovril Drug: Acetazolamide Drug: Rivastigmine tartrate Drug: Carbidopa/levodopa Device: abdominal binder Device: abdominal binder (sham)	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Subject), Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	Evaluation and Treatment of Autonomic Failure.

Resource links provided by NLM:

MedlinePlus related topics: Caffeine Drinking Water Low Blood Pressure

Drug Information available for: Ephedrine Hydrochloride Indomethacin 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione Promethazine hydrochloride Diphenhydramine Phenylephrine Acetazolamide Levodopa Promethazine Phenylephrine hydrochloride Caffeine citrate Tranylcypromine sulfate Ibuprofen Carbidopa Midodrine Midodrine hydrochloride Dexibuprofen Acarbose Sinemet Ranitidine Ranitidine Hydrochloride Modafinil Octreotide acetate Atomoxetine hydrochloride Atomoxetine Octreotide Diphenhydramine citrate Pyridostigmine bromide Ergotamine Methylphenidate Rivastigmine Ranitidine bismuth citrate SDZ-ENA 713 Celecoxib Yohimbine Diphenhydramine hydrochloride Tranylcypromine Pyridostigmine Methylphenidate hydrochloride Ephedrine Pseudoephedrine hydrochloride Ergotamine tartrate Acetazolamide sodium Oxymetazoline Oxymetazoline hydrochloride Pseudoephedrine Sulfate

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

Increase in seated systolic blood pressure 1-hr post drug compared to baseline. [ Time Frame: 1.5-4 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Increase in standing time 1-hr post drug compared to baseline [ Time Frame: 1.5-4 hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	500
Study Start Date:	March 2002
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: active intervention: Experimental pressor agents, acarbose, acetazolamide, carbidopa/levodopa, abdominal binder or bovril	Drug: Atomoxetine 10-50 mg, PO. Single dose. Alone or in combination with Yohimbine or Mestinon. Drug: Acarbose 25-100 mg, PO. Single dose. Drug: Pyridostigmine Bromide 30 mg-180 mg PO. Single dose. Alone or in combination with Yohimbine or atomoxetine. Drug: Yohimbine 2.7, 5.4 or 10.8 mg PO. Single dose. Alone or in combination with Atomoxetine or Pyridostigmine. Drug: Midodrine HCl 2.5, 5.0, 7.5, 10 mg PO. Single dose Drug: Modafinil 50-400 mg PO. Single dose Drug: Octreotide 5-50 µg, S.C. Single dose. Other: water intake Tap water 2 onz., 8 oz., 16 oz. PO, alone or in combination with any of the above medications. Single dose. Drug: Diphenhydramine Hydrochloride 12.5 mg-100 mg PO. Single dose. Alone or in combination with Ranitidine Drug: Ranitidine HCL 150-300 mg PO. Single dose. Alone or in combination with Diphenhydramine. Drug: Tranylcypromine 5 - 40 mg PO. Single dose Drug: Ergotamine/ Caffeine Ergotamine: 1.0 mg PO. Single dose. Caffeine 100 mg PO.Single dose Drug: Celecoxib 50-200 mg PO. Single dose Drug: Pseudoephedrine 15, 30 or 60 mg, PO. Single dose. Drug: Methylphenidate 5 or 10 mg PO. Single dose. Drug: Indomethacin 25, 50 or 75 mg, PO. Singe dose. Drug: Ibuprofen 300, 600 or 900 mg, PO. Single dose. Drug: Oxymetazoline 0.05% nasal solution 1-2 sprays/ nostril. Single dose. Dietary Supplement: Bovril 6-10 g, PO. Single dose. Drug: Acetazolamide 125-1000 mg PO. Single dose. Alone or in combination with yohimbine or midodrine Drug: Rivastigmine tartrate 1.5-6 mg PO. Single dose. Drug: Carbidopa/levodopa 10mg/100mg or 25mg/100mg. 1-2 tab PO. Single dose. Alone or in combination with carbidopa (Lodosyn) 25-175 mg Device: abdominal binder External abdominal compression (20-40 mm Hg) with an abdominal binder applied for 70 min before and after a pressor agent (e.g. midodrine, yohimbine).
2: Placebo or sham device: Placebo Comparator placebo pill or abdominal binder (sham)	Drug: placebo PO.Single dose. Device: abdominal binder (sham) External abdominal compression (5 mm Hg) with an abdominal binder applied for 70 min before and after a pressor agent (e.g. midodrine, yohimbine).

Arms

Assigned Interventions

1: active intervention: Experimental

pressor agents, acarbose, acetazolamide, carbidopa/levodopa, abdominal binder or bovril

Drug: Atomoxetine

10-50 mg, PO. Single dose. Alone or in combination with Yohimbine or Mestinon.

Drug: Acarbose

25-100 mg, PO. Single dose.

Drug: Pyridostigmine Bromide

30 mg-180 mg PO. Single dose. Alone or in combination with Yohimbine or atomoxetine.

Drug: Yohimbine

2.7, 5.4 or 10.8 mg PO. Single dose. Alone or in combination with Atomoxetine or Pyridostigmine.

Drug: Midodrine HCl

2.5, 5.0, 7.5, 10 mg PO. Single dose

Drug: Modafinil

50-400 mg PO. Single dose

Drug: Octreotide

5-50 µg, S.C. Single dose.

Other: water intake

Tap water 2 onz., 8 oz., 16 oz. PO, alone or in combination with any of the above medications. Single dose.

Drug: Diphenhydramine Hydrochloride

12.5 mg-100 mg PO. Single dose. Alone or in combination with Ranitidine

Drug: Ranitidine HCL

150-300 mg PO. Single dose. Alone or in combination with Diphenhydramine.

Drug: Tranylcypromine

5 - 40 mg PO. Single dose

Drug: Ergotamine/ Caffeine

Ergotamine: 1.0 mg PO. Single dose. Caffeine 100 mg PO.Single dose

Drug: Celecoxib

50-200 mg PO. Single dose

Drug: Pseudoephedrine

15, 30 or 60 mg, PO. Single dose.

Drug: Methylphenidate

5 or 10 mg PO. Single dose.

Drug: Indomethacin

25, 50 or 75 mg, PO. Singe dose.

Drug: Ibuprofen

300, 600 or 900 mg, PO. Single dose.

Drug: Oxymetazoline 0.05% nasal solution

1-2 sprays/ nostril. Single dose.

Dietary Supplement: Bovril

6-10 g, PO. Single dose.

Drug: Acetazolamide

125-1000 mg PO. Single dose. Alone or in combination with yohimbine or midodrine

Drug: Rivastigmine tartrate

1.5-6 mg PO. Single dose.

Drug: Carbidopa/levodopa

10mg/100mg or 25mg/100mg. 1-2 tab PO. Single dose. Alone or in combination with carbidopa (Lodosyn) 25-175 mg

Device: abdominal binder

External abdominal compression (20-40 mm Hg) with an abdominal binder applied for 70 min before and after a pressor agent (e.g. midodrine, yohimbine).

2: Placebo or sham device: Placebo Comparator

placebo pill or abdominal binder (sham)

Drug: placebo

PO.Single dose.

Device: abdominal binder (sham)

External abdominal compression (5 mm Hg) with an abdominal binder applied for 70 min before and after a pressor agent (e.g. midodrine, yohimbine).

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients referred for evaluation of their autonomic function
Ages 18-85

Exclusion Criteria:

Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00223691

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: Biaggioni Italo, MD
Sub-Investigator: Cyndya Shibao, MD
Sub-Investigator: David Robertson, MD
Sub-Investigator: Andre Diedrich, MD
Sub-Investigator: Alfredo Gamboa, MD
Sub-Investigator: Satish Raj, MD
Sub-Investigator: Kyoko Sato, MD
Sub-Investigator: Luis E Okamoto, MD
Sub-Investigator: Hossam Mustafa, MD

Sponsors and Collaborators

Vanderbilt University

Investigators

Principal Investigator:

Italo Biaggioni, MD

Vanderbilt University

More Information

Additional Information:

Autonomic Dysfunction Center Website This link exits the ClinicalTrials.gov site

Publications:

Jordan J, Shannon JR, Biaggioni I, Norman R, Black BK, Robertson D. Contrasting actions of pressor agents in severe autonomic failure. Am J Med. 1998 Aug;105(2):116-24.

Shibao C, Gamboa A, Diedrich A, Biaggioni I. Management of hypertension in the setting of autonomic failure: a pathophysiological approach. Hypertension. 2005 Apr;45(4):469-76. Epub 2005 Feb 28.

Shibao C, Arzubiaga C, Roberts LJ 2nd, Raj S, Black B, Harris P, Biaggioni I. Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension. 2005 Mar;45(3):385-90. Epub 2005 Feb 14.

Jordan J, Shannon JR, Diedrich A, Black B, Robertson D, Biaggioni I. Water potentiates the pressor effect of ephedra alkaloids. Circulation. 2004 Apr 20;109(15):1823-5. Epub 2004 Apr 5.

Jacob G, Costa F, Biaggioni I. Spectrum of autonomic cardiovascular neuropathy in diabetes. Diabetes Care. 2003 Jul;26(7):2174-80. Erratum in: Diabetes Care. 2003 Sep;26(9):2708.

Biaggioni I, Robertson RM. Hypertension in orthostatic hypotension and autonomic dysfunction. Cardiol Clin. 2002 May;20(2):291-301, vii. Review.

Jordan J, Biaggioni I. Diagnosis and treatment of supine hypertension in autonomic failure patients with orthostatic hypotension. J Clin Hypertens (Greenwich). 2002 Mar-Apr;4(2):139-45.

Shannon JR, Diedrich A, Biaggioni I, Tank J, Robertson RM, Robertson D, Jordan J. Water drinking as a treatment for orthostatic syndromes. Am J Med. 2002 Apr 1;112(5):355-60.

Jordan J, Shannon JR, Black BK, Ali Y, Farley M, Costa F, Diedrich A, Robertson RM, Biaggioni I, Robertson D. The pressor response to water drinking in humans : a sympathetic reflex? Circulation. 2000 Feb 8;101(5):504-9.

Shibao C, Gamboa A, Diedrich A, Dossett C, Choi L, Farley G, Biaggioni I. Acarbose, an alpha-glucosidase inhibitor, attenuates postprandial hypotension in autonomic failure. Hypertension. 2007 Jul;50(1):54-61. Epub 2007 May 21.

Shibao C, Raj SR, Gamboa A, Diedrich A, Choi L, Black BK, Robertson D, Biaggioni I. Norepinephrine transporter blockade with atomoxetine induces hypertension in patients with impaired autonomic function. Hypertension. 2007 Jul;50(1):47-53. Epub 2007 May 21.

Responsible Party:	Vanderbilt University ( Italo Biaggioni )
Study ID Numbers:	000814, HL46681
Study First Received:	September 14, 2005
Last Updated:	August 14, 2009
ClinicalTrials.gov Identifier:	NCT00223691 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:

orthostatic hypotension
autonomic failure

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Neurotransmitter Agents
Adrenergic Agents
Anti-Dyskinesia Agents
Diuretics
Anesthetics
Promethazine
Pyridostigmine Bromide
Antipruritics
Dermatologic Agents
Antidepressive Agents
Sympathomimetics
Nervous System Diseases
Cyclooxygenase Inhibitors
Anti-Allergic Agents

Histamine H2 Antagonists
Natriuretic Agents
Histamine H1 Antagonists
Bronchodilator Agents
Respiratory System Agents
Neurotransmitter Uptake Inhibitors
Immunologic Factors
Rivastigmine
Antineoplastic Agents
Acetazolamide
Antiparkinson Agents
Tranylcypromine
Gout Suppressants
Modafinil
Adrenergic Agonists

ClinicalTrials.gov processed this record on November 27, 2009