Treatment of Orthostatic Intolerance

NCT00262470 | Active Not Recruiting Phase 1

• 2 other identifiers: 008397UL1TR000445
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Tachycardia; Chronic Orthostatic Intolerance

Keywords

tachycardia; sinus tachycardia; postural tachycardia syndrome (POTS)

Outcome Measures

Primary Outcomes (1)

• Increase in heart rate with standing

  1-4 hours

Secondary Outcomes (5)

• Sitting heart rate

  1-4 hours

• Standing heart rate

  1-4 hours

• Blood pressure

  1-4 hours

• Decrease in blood pressure with standing

  1-4 hours

• Orthostatic symptoms score

  Baseline, 2h, 4h

Study Arms (20)

1

EXPERIMENTAL

Acetazolamide

Drug: Acetazolamide

2

EXPERIMENTAL

Atomoxetine

Drug: Atomoxetine; Drug: Atomoxetine & Propranolol

3

EXPERIMENTAL

NO Drug

Other: NO Drug

4

EXPERIMENTAL

Clonidine

Drug: Clonidine

5

EXPERIMENTAL

Entacapone

Drug: Entacapone; Drug: Entacapone & Propranolol

6

EXPERIMENTAL

Indomethacin

Drug: Indomethacin

7

EXPERIMENTAL

Isosorbide Dinitrate

Drug: Isosorbide Dinitrate

8

EXPERIMENTAL

Mecamylamine

Drug: Mecamylamine

9

EXPERIMENTAL

Memantine

Drug: memantine

10

EXPERIMENTAL

Melatonin

Dietary Supplement: Melatonin

11

EXPERIMENTAL

Midodrine

Drug: Midodrine

12

EXPERIMENTAL

Modafinil

Drug: Modafinil; Drug: Modafinil & Propranolol

13

EXPERIMENTAL

Octreotide

Drug: Octreotide

14

PLACEBO COMPARATOR

Placebo (lactose tablet)

Radiation: Placebo

15

EXPERIMENTAL

Propranolol

Drug: Entacapone & Propranolol; Drug: Atomoxetine & Propranolol; Drug: Propranolol; Drug: Modafinil & Propranolol

16

EXPERIMENTAL

Sertraline

Drug: Sertraline

17

EXPERIMENTAL

Normal Saline (0.9%) 1 liter

Procedure: IV Saline

18

EXPERIMENTAL

Drinking Water

Other: Drinking Water

19

EXPERIMENTAL

Dead Space Breathing Device

Device: Breathing Device

Abdominal Binder

EXPERIMENTAL

Abdominal binder with inflatable pressure over abdomen

Device: Abdominal binder

Interventions

Acetazolamide DRUG

250 mg PO x 1

Also known as: Diamox

1

Atomoxetine DRUG

10-40 mg PO x 1 dose

Also known as: Strattera

2

NO Drug OTHER

No intervention - just monitoring

3

Clonidine DRUG

Clonidine 0.05-0.3 mg PO x 1 dose

Also known as: Catapres

4

Entacapone DRUG

Entacapone 200-400 mg PO x 1 dose

Also known as: Comtan

5

Entacapone & Propranolol DRUG

Entacapone 200-400 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose

Also known as: Comtan, Inderal

15; 5

Atomoxetine & Propranolol DRUG

Atomoxetine 10-40 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose

Also known as: Strattera, Inderal

15; 2

Indomethacin DRUG

Indomethacin 25-50 mg PO x 1 dose

Also known as: Indocin

6

Mecamylamine DRUG

mecamylamine 1.25-5 mg PO x 1 dose

Also known as: inversine

8

Isosorbide Dinitrate DRUG

Isosorbide dinitrate 5-20 mg PO x 1 dose

Also known as: Isordil

7

Melatonin DIETARY_SUPPLEMENT

melatonin 3 mg PO x 1 dose

10

Midodrine DRUG

midodrine 2.5-10 mg PO x 1 dose

Also known as: pro-amatine

11

Modafinil DRUG

modafinil 100-200 mg PO x 1 dose

Also known as: provigil

12

Octreotide DRUG

octreotide 12.5-50 mcg Subcutaneous x 1 dose

Also known as: sandostatin

13

Placebo RADIATION

lactose tablet x 1 pill

14

Propranolol DRUG

Propranolol 10-80 mg PO x 1-2 dose

Also known as: Inderal

15

Modafinil & Propranolol DRUG

Modafinil 100-200 mg PO x 1 dose AND Propranolol 20 mg PO x 1 dose

Also known as: Provigil, Inderal

12; 15

Sertraline DRUG

sertraline 25-50 mg PO x 1 dose

Also known as: Zoloft

16

IV Saline PROCEDURE

1 liter IV over 2 hours

Also known as: NaCl solution (0.9%)

17

Drinking Water OTHER

16 fluid ounces

18

Breathing Device DEVICE

Breathing through a dead space tube

19

memantine DRUG

memantine 5-20 mg PO x 1 dose

Also known as: Namenda

9

Abdominal binder DEVICE

Using large blood pressure cuffs linked together, they are wrapped around the subjects abdomen and inflated to generate increased pressure to below tolerably threshold.

Abdominal Binder

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic symptoms (\> 6 months) with standing upright

You may not qualify if:

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

Sponsors & Collaborators

• Satish R. Raj: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Vanderbilt University Autonomic Dysfunction Center

Nashville, Tennessee, 37232-2195, United States

Location

Related Publications (8)

• 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. doi: 10.1161/CIRCULATIONAHA.104.497594. Epub 2005 May 23.

  PMID: 15911704 RESULT

• 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.

  PMID: 19687359 RESULT

• Smith EC, Diedrich A, Raj SR, Gamboa A, Shibao CA, Black BK, Peltier A, Paranjape SY, Biaggioni I, Okamoto LE. Splanchnic Venous Compression Enhances the Effects of ss-Blockade in the Treatment of Postural Tachycardia Syndrome. J Am Heart Assoc. 2020 Jul 21;9(14):e016196. doi: 10.1161/JAHA.120.016196. Epub 2020 Jul 16.

  PMID: 32673517 DERIVED

• 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.

  PMID: 24721800 DERIVED

• 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.

  PMID: 24606242 DERIVED

• 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.

  PMID: 24495468 DERIVED

• 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.

  PMID: 24227635 DERIVED

• 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.

  PMID: 24002370 DERIVED

Related Links

• Vanderbilt University Autonomic Dysfunction Center website

MeSH Terms

Conditions

Tachycardia; Tachycardia, Sinus; Postural Orthostatic Tachycardia Syndrome

Interventions

Acetazolamide; Atomoxetine Hydrochloride; Clonidine; entacapone; Propranolol; Indomethacin; Mecamylamine; Isosorbide Dinitrate; Melatonin; Midodrine; Modafinil; Octreotide; Sertraline; Sodium Chloride; Saline Solution; Drinking Water; Memantine

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Tachycardia, Supraventricular; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propylamines; Amines; Imidazolines; Imidazoles; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Norbornanes; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Isosorbide; Sorbitol; Sugar Alcohols; Carbohydrates; Tryptamines; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Ethanolamines; Benzhydryl Compounds; Benzene Derivatives; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; 1-Naphthylamine; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Water; Hydroxides; Alkalies; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Amantadine; Adamantane

Study Officials

• Satish R Raj, MD MSCI

  Vanderbilt University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine & Pharmacology

Study Record Dates

• First Submitted: December 5, 2005
• First Posted: December 6, 2005
• Study Start: April 1, 1997
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 8, 2025

Record last verified: 2025-10

Locations

US (1)