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TachycardiaPhase 1/2NCT00262470

Treatment of Orthostatic Intolerance

A Phase 1/2 study testing Acetazolamide, Atomoxetine and NO Drug in people with Tachycardia and Chronic Orthostatic Intolerance, run by Satish R. Raj at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Tachycardia, Chronic Orthostatic Intolerance
What is being tested?
Acetazolamide, Atomoxetine and NO Drug
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
150 participants
Where
1 siteUnited States
Study dates
Apr 1997to Dec 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Chronic symptoms (> 6 months) with standing upright

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Vanderbilt University Autonomic Dysfunction Center

    Nashville, Tennessee, 37232-2195

Other trials in United States

About this study

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.

Read the detailed description

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.

Being tested
Acetazolamide, Atomoxetine, NO Drug, Clonidine, Entacapone
Keywords
tachycardia, sinus tachycardia, postural tachycardia syndrome (POTS)
Medical subject headings
Tachycardia, Tachycardia, Sinus, Postural Orthostatic Tachycardia Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AcetazolamideDrug

    Also called Diamox

    250 mg PO x 1

  • AtomoxetineDrug

    Also called Strattera

    10-40 mg PO x 1 dose

  • NO DrugOther

    No intervention - just monitoring

  • ClonidineDrug

    Also called Catapres

    Clonidine 0.05-0.3 mg PO x 1 dose

  • EntacaponeDrug

    Also called Comtan

    Entacapone 200-400 mg PO x 1 dose

  • Entacapone & PropranololDrug

    Also called Comtan, Inderal

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

  • Atomoxetine & PropranololDrug

    Also called Strattera, Inderal

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

  • IndomethacinDrug

    Also called Indocin

    Indomethacin 25-50 mg PO x 1 dose

  • MecamylamineDrug

    Also called inversine

    mecamylamine 1.25-5 mg PO x 1 dose

  • Isosorbide DinitrateDrug

    Also called Isordil

    Isosorbide dinitrate 5-20 mg PO x 1 dose

  • MelatoninDietary supplement

    melatonin 3 mg PO x 1 dose

  • MidodrineDrug

    Also called pro-amatine

    midodrine 2.5-10 mg PO x 1 dose

  • ModafinilDrug

    Also called provigil

    modafinil 100-200 mg PO x 1 dose

  • OctreotideDrug

    Also called sandostatin

    octreotide 12.5-50 mcg Subcutaneous x 1 dose

  • PlaceboRadiation

    lactose tablet x 1 pill

  • PropranololDrug

    Also called Inderal

    Propranolol 10-80 mg PO x 1-2 dose

  • Modafinil & PropranololDrug

    Also called Provigil, Inderal

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

  • SertralineDrug

    Also called Zoloft

    sertraline 25-50 mg PO x 1 dose

  • IV SalineProcedure or surgery

    Also called NaCl solution (0.9%)

    1 liter IV over 2 hours

  • Drinking WaterOther

    16 fluid ounces

  • Breathing DeviceDevice

    Breathing through a dead space tube

  • memantineDrug

    Also called Namenda

    memantine 5-20 mg PO x 1 dose

  • Abdominal binderDevice

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

Study groups in NCT00262470
Study groupRoleWhat they receive
1ExperimentalAcetazolamide
Receives: Drug: Acetazolamide
2ExperimentalAtomoxetine
Receives: Drug: Atomoxetine; Drug: Atomoxetine & Propranolol
3ExperimentalNO Drug
Receives: Other: NO Drug
4ExperimentalClonidine
Receives: Drug: Clonidine
5ExperimentalEntacapone
Receives: Drug: Entacapone; Drug: Entacapone & Propranolol
6ExperimentalIndomethacin
Receives: Drug: Indomethacin
7ExperimentalIsosorbide Dinitrate
Receives: Drug: Isosorbide Dinitrate
8ExperimentalMecamylamine
Receives: Drug: Mecamylamine
9ExperimentalMemantine
Receives: Drug: memantine
10ExperimentalMelatonin
Receives: Dietary Supplement: Melatonin
11ExperimentalMidodrine
Receives: Drug: Midodrine
12ExperimentalModafinil
Receives: Drug: Modafinil; Drug: Modafinil & Propranolol
13ExperimentalOctreotide
Receives: Drug: Octreotide
14Placebo comparatorPlacebo (lactose tablet)
Receives: Radiation: Placebo
15ExperimentalPropranolol
Receives: Drug: Entacapone & Propranolol; Drug: Atomoxetine & Propranolol; Drug: Propranolol; Drug: Modafinil & Propranolol
16ExperimentalSertraline
Receives: Drug: Sertraline
17ExperimentalNormal Saline (0.9%) 1 liter
Receives: Procedure: IV Saline
18ExperimentalDrinking Water
Receives: Other: Drinking Water
19ExperimentalDead Space Breathing Device
Receives: Device: Breathing Device
Abdominal BinderExperimentalAbdominal binder with inflatable pressure over abdomen
Receives: Device: Abdominal binder

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Increase in heart rate with standing

    Measured: 1-4 hours

Secondary outcomes (5)

  1. Sitting heart rate

    Measured: 1-4 hours

  2. Standing heart rate

    Measured: 1-4 hours

  3. Blood pressure

    Measured: 1-4 hours

  4. Decrease in blood pressure with standing

    Measured: 1-4 hours

  5. Orthostatic symptoms score

    Measured: Baseline, 2h, 4h

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2005 (estimated)
  2. Study startApr 1997
  3. Primary completionDec 2029 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00262470
Sponsor's protocol ID
008397
Other IDs
UL1TR000445
Status last verified
Oct 2026
First submitted
5 Dec 2005
Last updated
16 Oct 2026
Results posted
No
Data monitoring committee
No

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

    PubMed 15911704

  • 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.

    PubMed 19687359

  • 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.

    PubMed 32673517

  • 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.

    PubMed 24721800

  • 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.

    PubMed 24606242

  • 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.

    PubMed 24495468

  • 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.

    PubMed 24227635

  • 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.

    PubMed 24002370

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Acetazolamide, Atomoxetine and NO Drug in people with Tachycardia and Chronic Orthostatic Intolerance, run by Satish R. Raj at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Increase in heart rate with standing (time frame: 1-4 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00262470, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.

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