Treatment of Orthostatic Intolerance - Full Text View

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

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

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

Resource links provided by NLM:

Genetics Home Reference related topics: Brugada syndrome short QT syndrome

MedlinePlus related topics: Drinking Water Mitral Valve Prolapse Mobility Aids

Drug Information available for: Indomethacin Acetazolamide Mecamylamine Isosorbide-5-mononitrate Memantine Memantine hydrochloride Midodrine Midodrine hydrochloride Modafinil Octreotide acetate Sertraline hydrochloride Sertraline Atomoxetine hydrochloride Atomoxetine Octreotide Melatonin Isosorbide dinitrate OR 611 BaseLine Entacapone Propranolol hydrochloride Propranolol Isosorbide Mecamylamine hydrochloride Acetazolamide sodium Clonidine Clonidine hydrochloride Dexpropranolol

U.S. FDA Resources

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

Additional Information:

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

Publications:

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
Study First Received:	December 5, 2005
Last Updated:	June 23, 2009
ClinicalTrials.gov Identifier:	NCT00262470 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:

tachycardia
sinus tachycardia
postural tachycardia syndrome (POTS)

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Isosorbide
Neurotransmitter Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Anti-Dyskinesia Agents
Diuretics
Physiological Effects of Drugs
Isosorbide Dinitrate
Mecamylamine
Octreotide
Excitatory Amino Acid Agents
Cholinergic Agents
Pathologic Processes

Propranolol
Therapeutic Uses
Midodrine
Memantine
Cardiovascular Diseases
Antidepressive Agents
Neurocirculatory Asthenia
Heart Valve Prolapse
Heart Diseases
Antineoplastic Agents, Hormonal
Sympathomimetics
Tachycardia
Cyclooxygenase Inhibitors
Antihypertensive Agents
Heart Valve Diseases

ClinicalTrials.gov processed this record on November 27, 2009