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Autonomic Failure | Treatment of Orthostatic Hypotension in Autonomic Failure

Autonomic Failure research study

What is the primary objective of this study?

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.

Who is eligible to participate?

Inclusion Criteria: - Patients referred for evaluation of their autonomic function - Ages 18-85 Exclusion Criteria: - Pregnancy

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Autonomic Failure

Orthostatic Hypotension

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Atomoxetine10-50 mg, PO. Single dose. Alone or in combination with Yohimbine or Mestinon.

Drug:Acarbose25-100 mg, PO. Single dose.

Drug:Pyridostigmine Bromide30 mg-180 mg PO. Single dose. Alone or in combination with Yohimbine or atomoxetine.

Drug:Yohimbine2.7, 5.4 or 10.8 mg PO. Single dose. Alone or in combination with Atomoxetine or Pyridostigmine.

Drug:Midodrine HCl2.5, 5.0, 7.5, 10 mg PO. Single dose

Drug:placeboPO.Single dose.

Drug:Modafinil50-400 mg PO. Single dose

Drug:Octreotide5-50 µg, S.C. Single dose.

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

Drug:Diphenhydramine Hydrochloride12.5 mg-100 mg PO. Single dose. Alone or in combination with Ranitidine

Drug:Ranitidine HCL150-300 mg PO. Single dose. Alone or in combination with Diphenhydramine.

Drug:Tranylcypromine5 - 40 mg PO. Single dose

Drug:Ergotamine/ CaffeineErgotamine: 1.0 mg PO. Single dose. Caffeine 100 mg PO.Single dose

Drug:Celecoxib50-200 mg PO. Single dose

Drug:Pseudoephedrine15, 30 or 60 mg, PO. Single dose.

Drug:Methylphenidate5 or 10 mg PO. Single dose.

Drug:Indomethacin25, 50 or 75 mg, PO. Singe dose.

Drug:Ibuprofen300, 600 or 900 mg, PO. Single dose.

Drug:Oxymetazoline 0.05% nasal solution1-2 sprays/ nostril. Single dose.

Dietary Supplement:Bovril6-10 g, PO. Single dose.

Drug:Acetazolamide125-1000 mg PO. Single dose. Alone or in combination with yohimbine or midodrine

Drug:Rivastigmine tartrate1.5-6 mg PO. Single dose.

Drug:Carbidopa/levodopa10mg/100mg or 25mg/100mg. 1-2 tab PO. Single dose. Alone or in combination with carbidopa (Lodosyn) 25-175 mg

Device:Inflatable abdominal binderExternal abdominal compression (20-40 mm Hg) with an inflatable abdominal binder applied after a pressor agent (e.g. midodrine, yohimbine).

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).

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

1: active interventionatomoxetine, 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

2: Placebo or sham deviceplacebo pill or inflatable abdominal binder (sham)

Study Status

Completed

Start Date: March 2002

Completed Date: January 2017

Phase: Phase 1

Type: Interventional

Design:

Primary Outcome: Increase in seated systolic blood pressure 1-hr post drug compared to baseline.

Secondary Outcome: Increase in standing time 1-hr post drug compared to baseline

Study sponsors, principal investigator, and references

Principal Investigator: Italo Biaggioni, MD

Lead Sponsor: Vanderbilt University

Collaborator:

More information:https://clinicaltrials.gov/show/NCT00223691

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.

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.

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