Treatment of Orthostatic Intolerance

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ClinicalTrials.gov Identifier: NCT00262470

Recruitment Status : Active, not recruiting

First Posted : December 6, 2005

Last Update Posted : August 21, 2019

Sponsor:

Collaborator:

National Institutes of Health (NIH)

Information provided by (Responsible Party):

Satish R. Raj, Vanderbilt University

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Tachycardia Chronic Orthostatic Intolerance	Drug: Acetazolamide Drug: Atomoxetine Other: 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 Device: Abdominal binder	Phase 1 Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	150 participants
Allocation:	Non-Randomized
Intervention Model:	Crossover Assignment
Masking:	Single (Participant)
Primary Purpose:	Treatment
Official Title:	Treatment of Orthostatic Intolerance
Actual Study Start Date :	April 1997
Estimated Primary Completion Date :	December 2022
Estimated Study Completion Date :	December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 Acetazolamide	Drug: Acetazolamide 250 mg PO x 1 Other Name: Diamox
Experimental: 2 Atomoxetine	Drug: Atomoxetine 10-40 mg PO x 1 dose Other Name: Strattera Drug: Atomoxetine & Propranolol Atomoxetine 10-40 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose Other Names: Strattera Inderal
Experimental: 3 NO Drug	Other: NO Drug No intervention - just monitoring
Experimental: 4 Clonidine	Drug: Clonidine Clonidine 0.05-0.3 mg PO x 1 dose Other Name: Catapres
Experimental: 5 Entacapone	Drug: Entacapone Entacapone 200-400 mg PO x 1 dose Other Name: Comtan Drug: Entacapone & Propranolol Entacapone 200-400 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose Other Names: Comtan Inderal
Experimental: 6 Indomethacin	Drug: Indomethacin Indomethacin 25-50 mg PO x 1 dose Other Name: Indocin
Experimental: 7 Isosorbide Dinitrate	Drug: Isosorbide Dinitrate Isosorbide dinitrate 5-20 mg PO x 1 dose Other Name: Isordil
Experimental: 8 Mecamylamine	Drug: Mecamylamine mecamylamine 1.25-5 mg PO x 1 dose Other Name: inversine
Experimental: 9 Memantine	Drug: memantine memantine 5-20 mg PO x 1 dose Other Name: Namenda
Experimental: 10 Melatonin	Dietary Supplement: Melatonin melatonin 3 mg PO x 1 dose
Experimental: 11 Midodrine	Drug: Midodrine midodrine 2.5-10 mg PO x 1 dose Other Name: pro-amatine
Experimental: 12 Modafinil	Drug: Modafinil modafinil 100-200 mg PO x 1 dose Other Name: provigil Drug: Modafinil & Propranolol Modafinil 100-200 mg PO x 1 dose AND Propranolol 20 mg PO x 1 dose Other Names: Provigil Inderal
Experimental: 13 Octreotide	Drug: Octreotide octreotide 12.5-50 mcg Subcutaneous x 1 dose Other Name: sandostatin
Placebo Comparator: 14 Placebo (lactose tablet)	Radiation: Placebo lactose tablet x 1 pill
Experimental: 15 Propranolol	Drug: Entacapone & Propranolol Entacapone 200-400 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose Other Names: Comtan Inderal Drug: Atomoxetine & Propranolol Atomoxetine 10-40 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose Other Names: Strattera Inderal Drug: Propranolol Propranolol 10-80 mg PO x 1-2 dose Other Name: Inderal Drug: Modafinil & Propranolol Modafinil 100-200 mg PO x 1 dose AND Propranolol 20 mg PO x 1 dose Other Names: Provigil Inderal
Experimental: 16 Sertraline	Drug: Sertraline sertraline 25-50 mg PO x 1 dose Other Name: Zoloft
Experimental: 17 Normal Saline (0.9%) 1 liter	Procedure: IV Saline 1 liter IV over 2 hours Other Name: NaCl solution (0.9%)
Experimental: 18 Drinking Water	Other: Drinking Water 16 fluid ounces
Experimental: 19 Dead Space Breathing Device	Device: Breathing Device Breathing through a dead space tube
Experimental: Abdominal Binder Abdominal binder with inflatable pressure over abdomen	Device: Abdominal binder Using large blood pressure cuffs linked together, they are wrapped around the subjects abdomen and inflated to generate increased pressure to below tolerably threshold.

Outcome Measures

Primary Outcome Measures :

Increase in heart rate with standing [ Time Frame: 1-4 hours ]

Secondary Outcome Measures :

Sitting heart rate [ Time Frame: 1-4 hours ]
Standing heart rate [ Time Frame: 1-4 hours ]
Blood pressure [ Time Frame: 1-4 hours ]
Decrease in blood pressure with standing [ Time Frame: 1-4 hours ]
Orthostatic symptoms score [ Time Frame: Baseline, 2h, 4h ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
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

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): NCT00262470

Locations

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

Sponsors and Collaborators

Satish R. Raj

National Institutes of Health (NIH)

Investigators

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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 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.

Raj SR, Black BK, Biaggioni I, Paranjape SY, Ramirez M, Dupont WD, Robertson D. Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. Circulation. 2009 Sep 1;120(9):725-34. doi: 10.1161/CIRCULATIONAHA.108.846501. Epub 2009 Aug 17.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nwazue VC, Paranjape SY, Black BK, Biaggioni I, Diedrich A, Dupont WD, Robertson D, Raj SR. Postural tachycardia syndrome and inappropriate sinus tachycardia: role of autonomic modulation and sinus node automaticity. J Am Heart Assoc. 2014 Apr 10;3(2):e000700. doi: 10.1161/JAHA.113.000700.

Nwazue VC, Arnold AC, Raj V, Black BK, Biaggioni I, Paranjape SY, Orozco C, Dupont WD, Robertson D, Raj SR. Understanding the placebo effect in clinical trials for postural tachycardia syndrome. Clin Exp Pharmacol Physiol. 2014 May;41(5):325-30. doi: 10.1111/1440-1681.12221.

Green EA, Black BK, Biaggioni I, Paranjape SY, Bagai K, Shibao C, Okoye MC, Dupont WD, Robertson D, Raj SR. Melatonin reduces tachycardia in postural tachycardia syndrome: a randomized, crossover trial. Cardiovasc Ther. 2014 Jun;32(3):105-12. doi: 10.1111/1755-5922.12067.

Mar PL, Raj V, Black BK, Biaggioni I, Shibao CA, Paranjape SY, Dupont WD, Robertson D, Raj SR. Acute hemodynamic effects of a selective serotonin reuptake inhibitor in postural tachycardia syndrome: a randomized, crossover trial. J Psychopharmacol. 2014 Feb;28(2):155-61. doi: 10.1177/0269881113512911. Epub 2013 Nov 13.

Green EA, Raj V, Shibao CA, Biaggioni I, Black BK, Dupont WD, Robertson D, Raj SR. Effects of norepinephrine reuptake inhibition on postural tachycardia syndrome. J Am Heart Assoc. 2013 Sep 3;2(5):e000395. doi: 10.1161/JAHA.113.000395.

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Responsible Party:	Satish R. Raj, Assistant Professor of Medicine & Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00262470 History of Changes
Other Study ID Numbers:	008397 UL1TR000445 ( U.S. NIH Grant/Contract )
First Posted:	December 6, 2005 Key Record Dates
Last Update Posted:	August 21, 2019
Last Verified:	August 2019

Keywords provided by Satish R. Raj, Vanderbilt University:


tachycardia sinus tachycardia postural tachycardia syndrome (POTS)

Additional relevant MeSH terms:

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Orthostatic Intolerance Tachycardia Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Cardiac Conduction System Disease Pathologic Processes Primary Dysautonomias Autonomic Nervous System Diseases Nervous System Diseases Neurologic Manifestations Signs and Symptoms Indomethacin Octreotide Propranolol	Clonidine Mecamylamine Acetazolamide Isosorbide Isosorbide Dinitrate Isosorbide-5-mononitrate Midodrine Memantine Entacapone Melatonin Modafinil Sertraline Atomoxetine Hydrochloride Antioxidants Molecular Mechanisms of Pharmacological Action

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