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: 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 Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Treatment of Orthostatic Intolerance

Resource links provided by NLM:

Drug Information available for: Indomethacin Acetazolamide Mecamylamine Melatonin Isosorbide dinitrate Propranolol hydrochloride Propranolol Isosorbide Mecamylamine hydrochloride Acetazolamide sodium Clonidine Clonidine hydrochloride Isosorbide mononitrate Memantine Memantine hydrochloride Midodrine hydrochloride Modafinil Octreotide acetate Sertraline hydrochloride Sertraline Atomoxetine hydrochloride Atomoxetine Octreotide Armodafinil Entacapone

Genetic and Rare Diseases Information Center resources: Postural Orthostatic Tachycardia Syndrome

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 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations


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


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.

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.


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
Study First Received:	December 5, 2005
Last Updated:	August 15, 2016
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:


tachycardia sinus tachycardia postural tachycardia syndrome (POTS)

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on September 27, 2016