search
Back to results

Treatment of Orthostatic Intolerance

Primary Purpose

Tachycardia, Chronic Orthostatic Intolerance

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Acetazolamide
Atomoxetine
NO Drug
Clonidine
Entacapone
Entacapone & Propranolol
Atomoxetine & Propranolol
Indomethacin
Mecamylamine
Isosorbide Dinitrate
Melatonin
Midodrine
Modafinil
Octreotide
Placebo
Propranolol
Modafinil & Propranolol
Sertraline
IV Saline
Drinking Water
Breathing Device
memantine
Abdominal binder
Sponsored by
Satish R. Raj
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tachycardia focused on measuring tachycardia, sinus tachycardia, postural tachycardia syndrome (POTS)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Vanderbilt University Autonomic Dysfunction Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm 19

Arm 20

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

Abdominal Binder

Arm Description

Acetazolamide

Atomoxetine

NO Drug

Clonidine

Entacapone

Indomethacin

Isosorbide Dinitrate

Mecamylamine

Memantine

Melatonin

Midodrine

Modafinil

Octreotide

Placebo (lactose tablet)

Propranolol

Sertraline

Normal Saline (0.9%) 1 liter

Drinking Water

Dead Space Breathing Device

Abdominal binder with inflatable pressure over abdomen

Outcomes

Primary Outcome Measures

Increase in heart rate with standing

Secondary Outcome Measures

Sitting heart rate
Standing heart rate
Blood pressure
Decrease in blood pressure with standing
Orthostatic symptoms score

Full Information

First Posted
December 5, 2005
Last Updated
September 20, 2023
Sponsor
Satish R. Raj
Collaborators
National Center for Advancing Translational Sciences (NCATS)
search

1. Study Identification

Unique Protocol Identification Number
NCT00262470
Brief Title
Treatment of Orthostatic Intolerance
Official Title
Treatment of Orthostatic Intolerance
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 1997 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Satish R. Raj
Collaborators
National Center for Advancing Translational Sciences (NCATS)

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tachycardia, Chronic Orthostatic Intolerance
Keywords
tachycardia, sinus tachycardia, postural tachycardia syndrome (POTS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Satish R Raj, MD MSCI
Organizational Affiliation
Vanderbilt University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Autonomic Dysfunction Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2195
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15911704
Citation
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.
Results Reference
result
PubMed Identifier
19687359
Citation
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.
Results Reference
result
PubMed Identifier
32673517
Citation
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.
Results Reference
derived
PubMed Identifier
24721800
Citation
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.
Results Reference
derived
PubMed Identifier
24606242
Citation
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.
Results Reference
derived
PubMed Identifier
24495468
Citation
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.
Results Reference
derived
PubMed Identifier
24227635
Citation
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.
Results Reference
derived
PubMed Identifier
24002370
Citation
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.
Results Reference
derived
Links:
URL
https://www.vumc.org/autonomic-dysfunction-center/vanderbilt-autonomic-dysfunction
Description
Vanderbilt University Autonomic Dysfunction Center website

Learn more about this trial

Treatment of Orthostatic Intolerance

We'll reach out to this number within 24 hrs