Treatment of Orthostatic Intolerance

NCT ID: NCT00262470

Last Updated: 2025-10-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-04-30

Study Completion Date

2029-12-31

Brief Summary

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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.

Detailed Description

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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.

Pilot drug trials are 4h in duration from \~9am -1pm. Different short-acting medications will be used to determine their acute hemodynamic effects in patients with orthostatic intolerance.

Conditions

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Tachycardia Chronic Orthostatic Intolerance

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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1

Acetazolamide

Group Type EXPERIMENTAL

Acetazolamide

Intervention Type DRUG

250 mg PO x 1

2

Atomoxetine

Group Type EXPERIMENTAL

Atomoxetine

Intervention Type DRUG

10-40 mg PO x 1 dose

Atomoxetine & Propranolol

Intervention Type DRUG

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

3

NO Drug

Group Type EXPERIMENTAL

NO Drug

Intervention Type OTHER

No intervention - just monitoring

4

Clonidine

Group Type EXPERIMENTAL

Clonidine

Intervention Type DRUG

Clonidine 0.05-0.3 mg PO x 1 dose

5

Entacapone

Group Type EXPERIMENTAL

Entacapone

Intervention Type DRUG

Entacapone 200-400 mg PO x 1 dose

Entacapone & Propranolol

Intervention Type DRUG

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

6

Indomethacin

Group Type EXPERIMENTAL

Indomethacin

Intervention Type DRUG

Indomethacin 25-50 mg PO x 1 dose

7

Isosorbide Dinitrate

Group Type EXPERIMENTAL

Isosorbide Dinitrate

Intervention Type DRUG

Isosorbide dinitrate 5-20 mg PO x 1 dose

8

Mecamylamine

Group Type EXPERIMENTAL

Mecamylamine

Intervention Type DRUG

mecamylamine 1.25-5 mg PO x 1 dose

9

Memantine

Group Type EXPERIMENTAL

memantine

Intervention Type DRUG

memantine 5-20 mg PO x 1 dose

10

Melatonin

Group Type EXPERIMENTAL

Melatonin

Intervention Type DIETARY_SUPPLEMENT

melatonin 3 mg PO x 1 dose

11

Midodrine

Group Type EXPERIMENTAL

Midodrine

Intervention Type DRUG

midodrine 2.5-10 mg PO x 1 dose

12

Modafinil

Group Type EXPERIMENTAL

Modafinil

Intervention Type DRUG

modafinil 100-200 mg PO x 1 dose

Modafinil & Propranolol

Intervention Type DRUG

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

13

Octreotide

Group Type EXPERIMENTAL

Octreotide

Intervention Type DRUG

octreotide 12.5-50 mcg Subcutaneous x 1 dose

14

Placebo (lactose tablet)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type RADIATION

lactose tablet x 1 pill

15

Propranolol

Group Type EXPERIMENTAL

Entacapone & Propranolol

Intervention Type DRUG

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

Atomoxetine & Propranolol

Intervention Type DRUG

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

Propranolol

Intervention Type DRUG

Propranolol 10-80 mg PO x 1-2 dose

Modafinil & Propranolol

Intervention Type DRUG

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

16

Sertraline

Group Type EXPERIMENTAL

Sertraline

Intervention Type DRUG

sertraline 25-50 mg PO x 1 dose

17

Normal Saline (0.9%) 1 liter

Group Type EXPERIMENTAL

IV Saline

Intervention Type PROCEDURE

1 liter IV over 2 hours

18

Drinking Water

Group Type EXPERIMENTAL

Drinking Water

Intervention Type OTHER

16 fluid ounces

19

Dead Space Breathing Device

Group Type EXPERIMENTAL

Breathing Device

Intervention Type DEVICE

Breathing through a dead space tube

Abdominal Binder

Abdominal binder with inflatable pressure over abdomen

Group Type EXPERIMENTAL

Abdominal binder

Intervention Type 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.

Interventions

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Acetazolamide

250 mg PO x 1

Intervention Type DRUG

Atomoxetine

10-40 mg PO x 1 dose

Intervention Type DRUG

NO Drug

No intervention - just monitoring

Intervention Type OTHER

Clonidine

Clonidine 0.05-0.3 mg PO x 1 dose

Intervention Type DRUG

Entacapone

Entacapone 200-400 mg PO x 1 dose

Intervention Type DRUG

Entacapone & Propranolol

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

Intervention Type DRUG

Atomoxetine & Propranolol

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

Intervention Type DRUG

Indomethacin

Indomethacin 25-50 mg PO x 1 dose

Intervention Type DRUG

Mecamylamine

mecamylamine 1.25-5 mg PO x 1 dose

Intervention Type DRUG

Isosorbide Dinitrate

Isosorbide dinitrate 5-20 mg PO x 1 dose

Intervention Type DRUG

Melatonin

melatonin 3 mg PO x 1 dose

Intervention Type DIETARY_SUPPLEMENT

Midodrine

midodrine 2.5-10 mg PO x 1 dose

Intervention Type DRUG

Modafinil

modafinil 100-200 mg PO x 1 dose

Intervention Type DRUG

Octreotide

octreotide 12.5-50 mcg Subcutaneous x 1 dose

Intervention Type DRUG

Placebo

lactose tablet x 1 pill

Intervention Type RADIATION

Propranolol

Propranolol 10-80 mg PO x 1-2 dose

Intervention Type DRUG

Modafinil & Propranolol

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

Intervention Type DRUG

Sertraline

sertraline 25-50 mg PO x 1 dose

Intervention Type DRUG

IV Saline

1 liter IV over 2 hours

Intervention Type PROCEDURE

Drinking Water

16 fluid ounces

Intervention Type OTHER

Breathing Device

Breathing through a dead space tube

Intervention Type DEVICE

memantine

memantine 5-20 mg PO x 1 dose

Intervention Type DRUG

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.

Intervention Type DEVICE

Other Intervention Names

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Diamox Strattera Catapres Comtan Comtan Inderal Strattera Inderal Indocin inversine Isordil pro-amatine provigil sandostatin Inderal Provigil Inderal Zoloft NaCl solution (0.9%) Namenda

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role collaborator

Satish R. Raj

OTHER

Sponsor Role lead

Responsible Party

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Satish R. Raj

Assistant Professor of Medicine & Pharmacology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Satish R Raj, MD MSCI

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University School of Medicine

Locations

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Vanderbilt University Autonomic Dysfunction Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 15911704 (View on PubMed)

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.

Reference Type RESULT
PMID: 19687359 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32673517 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24721800 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24606242 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24495468 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24227635 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24002370 (View on PubMed)

Related Links

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https://www.vumc.org/autonomic-dysfunction-center/vanderbilt-autonomic-dysfunction

Vanderbilt University Autonomic Dysfunction Center website

Other Identifiers

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008397

Identifier Type: -

Identifier Source: org_study_id

UL1TR000445

Identifier Type: NIH

Identifier Source: secondary_id

View Link

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