Treatment of Orthostatic Intolerance - Full Text View

Purpose

This trial is designed to study the effects of various mechanistically unique medications in controlling excessive increases in heart rate with standing and in improving the symptoms of orthostatic intolerance in patients with this disorder.

Condition	Intervention	Phase
Tachycardia Chronic Orthostatic Intolerance	Drug: Acetazolamide Drug: Atomoxetine Other: Baseline (No Drug) Drug: Clonidine Drug: Entacapone Drug: Entacapone & Propranolol Drug: Atomoxetine & Propranolol Drug: Indomethacin Drug: Mecamylamine Drug: Isosorbide Dinitrate Dietary Supplement: Melatonin Drug: Midodrine Drug: Modafinil Drug: Octreotide Radiation: Placebo Drug: Propranolol Drug: Modafinil & Propranolol Drug: Sertraline Procedure: IV Saline Other: Drinking Water Device: Breathing Device Drug: memantine	Phase I Phase II

Genetics Home Reference related topics:

Brugada syndrome short QT syndrome

MedlinePlus related topics:

Drinking Water Mitral Valve Prolapse Mobility Aids

ChemIDplus related topics:

Sertraline hydrochloride Sertraline Modafinil Entacapone Sodium chloride Clonidine Lactose Octreotide Octreotide acetate Memantine Memantine hydrochloride Propranolol Dexpropranolol Propranolol hydrochloride Atomoxetine Atomoxetine hydrochloride Acetazolamide Acetazolamide sodium Isosorbide Isosorbide dinitrate Isosorbide-5-mononitrate Melatonin Mecamylamine Mecamylamine hydrochloride Indomethacin Clonidine hydrochloride OR 611 Midodrine Midodrine hydrochloride Proline BaseLine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Single Blind (Subject), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Official Title:	Treatment of Orthostatic Intolerance

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

Increase in heart rate with standing [ Time Frame: 1-4 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Sitting heart rate [ Time Frame: 1-4 hours ] [ Designated as safety issue: No ]
Standing heart rate [ Time Frame: 1-4 hours ] [ Designated as safety issue: No ]
Blood pressure [ Time Frame: 1-4 hours ] [ Designated as safety issue: No ]
Decrease in blood pressure with standing [ Time Frame: 1-4 hours ] [ Designated as safety issue: No ]
Orthostatic symptoms score [ Time Frame: Baseline, 2h, 4h ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	April 1997
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Acetazolamide	Drug: Acetazolamide 250 mg PO x 1
2: Experimental Atomoxetine	Drug: Atomoxetine 10-40 mg PO x 1 dose Drug: Atomoxetine & Propranolol Atomoxetine 10-40 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose
3: No Intervention NO Drug to look at natural history over 4 hour duration of follow-up	Other: Baseline (No Drug) No intervention - just monitoring
4: Experimental Clonidine	Drug: Clonidine Clonidine 0.05-0.3 mg PO x 1 dose
5: Experimental Entacapone	Drug: Entacapone Entacapone 200-400 mg PO x 1 dose Drug: Entacapone & Propranolol Entacapone 200-400 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose
6: Experimental Indomethacin	Drug: Indomethacin Indomethacin 25-50 mg PO x 1 dose
7: Experimental Isosorbide Dinitrate	Drug: Isosorbide Dinitrate Isosorbide dinitrate 5-20 mg PO x 1 dose
8: Experimental Mecamylamine	Drug: Mecamylamine mecamylamine 1.25-5 mg PO x 1 dose
9: Experimental Memantine	Drug: memantine memantine 5-20 mg PO x 1 dose
10: Experimental Melatonin	Dietary Supplement: Melatonin melatonin 3 mg PO x 1 dose
11: Experimental Midodrine	Drug: Midodrine midodrine 2.5-10 mg PO x 1 dose
12: Experimental Modafinil	Drug: Modafinil modafinil 100-200 mg PO x 1 dose Drug: Modafinil & Propranolol Modafinil 100-200 mg PO x 1 dose AND Propranolol 20 mg PO x 1 dose
13: Experimental Octreotide	Drug: Octreotide octreotide 12.5-50 mcg Subcutaneous x 1 dose
14: Placebo Comparator Placebo (lactose tablet)	Radiation: Placebo lactose tablet x 1 pill
15: Experimental Propranolol	Drug: Entacapone & Propranolol Entacapone 200-400 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose Drug: Atomoxetine & Propranolol Atomoxetine 10-40 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose Drug: Propranolol Propranolol 10-80 mg PO x 1-2 dose Drug: Modafinil & Propranolol Modafinil 100-200 mg PO x 1 dose AND Propranolol 20 mg PO x 1 dose
16: Experimental Sertraline	Drug: Sertraline sertraline 25-50 mg PO x 1 dose
17: Experimental Normal Saline (0.9%) 1 liter	Procedure: IV Saline 1 liter IV over 2 hours
18: Experimental Drinking Water	Other: Drinking Water 16 fluid ounces
19: Experimental Dead Space Breathing Device	Device: Breathing Device Breathing through a dead space tube

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Chronic symptoms (> 6 months) with standing upright

Exclusion Criteria:

Obvious cause of hypovolemia or drugs that could worsen tachycardia
Chronic severe medical conditions such as cancer or ischemic heart disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262470

Contacts


Contact: Bonnie K Black, RN NP		adcresearch@vanderbilt.edu

Locations


United States, Tennessee
	Vanderbilt University Autonomic Dysfunction Center	Recruiting
	Nashville, Tennessee, United States, 37232-2195

Sponsors and Collaborators

Vanderbilt University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators


Principal Investigator:	Satish R Raj, MD MSCI	Vanderbilt University School of Medicine

More Information

Vanderbilt University Autonomic Dysfunction Center website This link exits the ClinicalTrials.gov site

Publications of Results:

Raj SR, Black BK, Biaggioni I, Harris PA, Robertson D. Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome. Circulation. 2005 May 31;111(21):2734-40. Epub 2005 May 23.

Responsible Party:	Vanderbilt University ( Satish Raj MD MSCI )
Study ID Numbers:	008397, GCRC 758, GCRC 1689
First Received:	December 5, 2005
Last Updated:	June 2, 2008
ClinicalTrials.gov Identifier:	NCT00262470
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:

tachycardia

sinus tachycardia

postural tachycardia syndrome (POTS)

Study placed in the following topic categories:

Isosorbide

Isosorbide-5-mononitrate

Acetazolamide

Mecamylamine

Octreotide

Atomoxetine

Isosorbide Dinitrate

Modafinil

Dopamine

Propranolol

Mental Disorders

Indomethacin

Midodrine

Memantine

Sertraline

Melatonin

Neurocirculatory Asthenia

Excitatory Amino Acids

Tachycardia, Sinus

Heart Diseases

Orthostatic intolerance

Asthenia

Tachycardia

Clonidine

Prolapse

Serotonin

Heart Valve Diseases

Entacapone

Nitric Oxide

Anxiety Disorders

Additional relevant MeSH terms:

Anti-Inflammatory Agents

Neurotransmitter Agents

Adrenergic Agents

Molecular Mechanisms of Pharmacological Action

Cholinergic Antagonists

Anti-Dyskinesia Agents

Diuretics

Physiological Effects of Drugs

Excitatory Amino Acid Agents

Cholinergic Agents

Pathologic Processes

Therapeutic Uses

Cardiovascular Diseases

Antidepressive Agents

Heart Valve Prolapse

Antineoplastic Agents, Hormonal

Sympathomimetics

Cyclooxygenase Inhibitors

Antihypertensive Agents

Carbonic Anhydrase Inhibitors

Natriuretic Agents

Adrenergic Antagonists

Neurotransmitter Uptake Inhibitors

Vasodilator Agents

Antioxidants

Adrenergic Uptake Inhibitors

Antineoplastic Agents

Nicotinic Antagonists

Psychotropic Drugs

Antiparkinson Agents

ClinicalTrials.gov processed this record on September 05, 2008

Sponsors and Collaborators:	Vanderbilt University National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00262470