Official Title: “Treatment of Orthostatic Intolerance”

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.

Study Type: Interventional

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

Study Primary Completion Date: January 2011

Intervention(s) in this Clinical Trial

• Drug: Acetazolamide
  • 250 mg PO x 1
• Drug: Atomoxetine
  • 10-40 mg PO x 1 dose
• Other: Baseline (No Drug)
  • No intervention - just monitoring
• Drug: Clonidine
  • Clonidine 0.05-0.3 mg PO x 1 dose
• 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
• Drug: Atomoxetine & Propranolol
  • Atomoxetine 10-40 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose
• Drug: Indomethacin
  • Indomethacin 25-50 mg PO x 1 dose
• Drug: Mecamylamine
  • mecamylamine 1.25-5 mg PO x 1 dose
• Drug: Isosorbide Dinitrate
  • Isosorbide dinitrate 5-20 mg PO x 1 dose
• Dietary Supplement: Melatonin
  • melatonin 3 mg PO x 1 dose
• Drug: Midodrine
  • midodrine 2.5-10 mg PO x 1 dose
• Drug: Modafinil
  • modafinil 100-200 mg PO x 1 dose
• Drug: Octreotide
  • octreotide 12.5-50 mcg Subcutaneous x 1 dose
• Radiation: Placebo
  • lactose tablet x 1 pill
• 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
• Drug: Sertraline
  • sertraline 25-50 mg PO x 1 dose
• Procedure: IV Saline
  • 1 liter IV over 2 hours
• Other: Drinking Water
  • 16 fluid ounces
• Device: Breathing Device
  • Breathing through a dead space tube
• Drug: memantine
  • memantine 5-20 mg PO x 1 dose

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Acetazolamide
• Experimental: 2
  • Atomoxetine
• No Intervention: 3
  • NO Drug to look at natural history over 4 hour duration of follow-up
• Experimental: 4
  • Clonidine
• Experimental: 5
  • Entacapone
• Experimental: 6
  • Indomethacin
• Experimental: 7
  • Isosorbide Dinitrate
• Experimental: 8
  • Mecamylamine
• Experimental: 9
  • Memantine
• Experimental: 10
  • Melatonin
• Experimental: 11
  • Midodrine
• Experimental: 12
  • Modafinil
• Experimental: 13
  • Octreotide
• Placebo Comparator: 14
  • Placebo (lactose tablet)
• Experimental: 15
  • Propranolol
• Experimental: 16
  • Sertraline
• Experimental: 17
  • Normal Saline (0.9%) 1 liter
• Experimental: 18
  • Drinking Water
• Experimental: 19
  • Dead Space Breathing Device

Primary Measures

• Increase in heart rate with standing
  • Time Frame: 1-4 hours
    Safety Issue?: No

Secondary Measures

• Sitting heart rate
  • Time Frame: 1-4 hours
    Safety Issue?: No
• Standing heart rate
  • Time Frame: 1-4 hours
    Safety Issue?: No
• Blood pressure
  • Time Frame: 1-4 hours
    Safety Issue?: No
• Decrease in blood pressure with standing
  • Time Frame: 1-4 hours
    Safety Issue?: No
• Orthostatic symptoms score
  • Time Frame: Baseline, 2h, 4h
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Vanderbilt University

Overall Clinical Trial Officials and Contacts

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

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

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00262470

Study ID Number: 008397

ClinicalTrials.gov Identifier: NCT00262470

Health Authority: United States: Institutional Review Board

Vanderbilt University Autonomic Dysfunction Center website