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Treatment of Orthostatic Hypotension in Autonomic Failure

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00223691
First Posted: September 22, 2005
Last Update Posted: January 18, 2017
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.
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University
  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: Inflatable abdominal binder Device: inflatable abdominal binder (sham) Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Official Title: Evaluation and Treatment of Autonomic Failure.

Resource links provided by NLM:


Further study details as provided by Italo Biaggioni, Vanderbilt University:

Primary Outcome Measures:
  • Increase in seated systolic blood pressure 1-hr post drug compared to baseline. [ Time Frame: 1.5-4 hours ]

Secondary Outcome Measures:
  • Increase in standing time 1-hr post drug compared to baseline [ Time Frame: 1.5-4 hours ]

Enrollment: 389
Study Start Date: March 2002
Study Completion Date: January 2017
Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1: active intervention
atomoxetine, pyridostigmine bromide, yohimbine, midodrine hcl, modafinil, octreotide, water intake, ranitidine hcl, diphenhydramine hydrochloride, tranylcypromine, ergotamine/ caffeine, celecoxib, pseudoephedrine, methylphenidate, indomethacin, ibuprofen, Oxymetazoline 0.05% nasal solution, acarbose, Rivastigmine tartrate, acetazolamide, carbidopa/levodopa, inflatable abdominal binder or bovril
Drug: Atomoxetine
10-50 mg, PO. Single dose. Alone or in combination with Yohimbine or Mestinon.
Other Name: Strattera
Drug: Acarbose
25-100 mg, PO. Single dose.
Other Name: Precose
Drug: Pyridostigmine Bromide
30 mg-180 mg PO. Single dose. Alone or in combination with Yohimbine or atomoxetine.
Other Name: Mestinon
Drug: Yohimbine
2.7, 5.4 or 10.8 mg PO. Single dose. Alone or in combination with Atomoxetine or Pyridostigmine.
Other Name: Yocon
Drug: Midodrine HCl
2.5, 5.0, 7.5, 10 mg PO. Single dose
Other Name: ProAmatine
Drug: Modafinil
50-400 mg PO. Single dose
Other Name: Provigil
Drug: Octreotide
5-50 µg, S.C. Single dose.
Other Name: Sandostatin
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
Other Name: Benadryl
Drug: Ranitidine HCL
150-300 mg PO. Single dose. Alone or in combination with Diphenhydramine.
Other Name: zantac
Drug: Tranylcypromine
5 - 40 mg PO. Single dose
Other Name: Parnate
Drug: Ergotamine/ Caffeine
Ergotamine: 1.0 mg PO. Single dose. Caffeine 100 mg PO.Single dose
Other Name: Cafergot
Drug: Celecoxib
50-200 mg PO. Single dose
Other Name: Celebrex
Drug: Pseudoephedrine
15, 30 or 60 mg, PO. Single dose.
Other Name: Sudafed
Drug: Methylphenidate
5 or 10 mg PO. Single dose.
Other Name: Ritalin
Drug: Indomethacin
25, 50 or 75 mg, PO. Singe dose.
Other Name: Indocin
Drug: Ibuprofen
300, 600 or 900 mg, PO. Single dose.
Other Name: Advil, Motrin
Drug: Oxymetazoline 0.05% nasal solution
1-2 sprays/ nostril. Single dose.
Other Name: Afrin
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
Other Name: Diamox
Drug: Rivastigmine tartrate
1.5-6 mg PO. Single dose.
Other Name: Exelon
Drug: Carbidopa/levodopa
10mg/100mg or 25mg/100mg. 1-2 tab PO. Single dose. Alone or in combination with carbidopa (Lodosyn) 25-175 mg
Other Name: Sinemet, Lodosyn
Device: Inflatable abdominal binder
External abdominal compression (20-40 mm Hg) with an inflatable abdominal binder applied after a pressor agent (e.g. midodrine, yohimbine).
Other Name: external abdominal compression
Placebo Comparator: 2: Placebo or sham device
placebo pill or inflatable abdominal binder (sham)
Drug: placebo
PO.Single dose.
Device: inflatable abdominal binder (sham)
External abdominal compression (5 mm Hg) with an inflatable abdominal binder applied after a pressor agent (e.g. midodrine, yohimbine).
Other Name: external abdominal compression (sham)

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Pregnancy
  Contacts and Locations
Information from the National Library of Medicine

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): NCT00223691


Locations
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Italo Biaggioni, MD Vanderbilt University
  More Information

Additional Information:
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.
Shibao C, Okamoto LE, Gamboa A, Yu C, Diedrich A, Raj SR, Robertson D, Biaggioni I. Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. 2010 Nov;56(5):847-51. doi: 10.1161/HYPERTENSIONAHA.110.154898. Epub 2010 Sep 13.
Okamoto LE, Shibao C, Gamboa A, Choi L, Diedrich A, Raj SR, Black BK, Robertson D, Biaggioni I. Synergistic effect of norepinephrine transporter blockade and α-2 antagonism on blood pressure in autonomic failure. Hypertension. 2012 Mar;59(3):650-6. doi: 10.1161/HYPERTENSIONAHA.111.184812. Epub 2012 Feb 6.
Shibao C, Okamoto L, Biaggioni I. Pharmacotherapy of autonomic failure. Pharmacol Ther. 2012 Jun;134(3):279-86. doi: 10.1016/j.pharmthera.2011.05.009. Epub 2011 Jun 12. Review.
Garland EM, Hooper WB, Robertson D. Pure autonomic failure. Handb Clin Neurol. 2013;117:243-57. doi: 10.1016/B978-0-444-53491-0.00020-1. Review.
Arnold AC, Biaggioni I. Management approaches to hypertension in autonomic failure. Curr Opin Nephrol Hypertens. 2012 Sep;21(5):481-5. doi: 10.1097/MNH.0b013e328356c52f. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00223691     History of Changes
Other Study ID Numbers: 000814
HL46681
First Submitted: September 14, 2005
First Posted: September 22, 2005
Last Update Posted: January 18, 2017
Last Verified: January 2017

Keywords provided by Italo Biaggioni, Vanderbilt University:
orthostatic hypotension
autonomic failure

Additional relevant MeSH terms:
Hypotension
Hypotension, Orthostatic
Pure Autonomic Failure
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Ibuprofen
Celecoxib
Indomethacin
Ergotamine
Caffeine
Carbidopa
Rivastigmine
Acetazolamide
Acarbose
Pyridostigmine Bromide
Tranylcypromine
Diphenhydramine
Methylphenidate
Modafinil
Armodafinil
Ephedrine
Levodopa
Carbidopa, levodopa drug combination
Atomoxetine Hydrochloride
Promethazine
Ranitidine


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