Treatment of Orthostatic Hypotension in Autonomic Failure

Summary

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.

Conditions

• Autonomic Failure
• Orthostatic Hypotension

Interventions

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

placebo

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

Inflatable abdominal binder

External 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).

Sponsors & Collaborators

• Vanderbilt University

  lead OTHER

Principal Investigators

• Italo Biaggioni, MD · Vanderbilt University

Study Design

Allocation

RANDOMIZED

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2002-03-31

Primary Completion

2017-01-31

Completion

2017-01-31

Countries

• United States

Study Locations