Multiple Interventions for Orthostatic Intolerance

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Satish R. Raj

Must not be taking: Tachycardia-inducing drugs

Disqualifiers: Cancer, Ischemic heart disease, others

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

150 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those taking drugs that could worsen fast heart rates. It's best to discuss your current medications with the trial team.

What evidence supports the effectiveness of clonidine as a drug for orthostatic intolerance?

Research shows that clonidine, an alpha2-agonist, can facilitate habituation of the acoustic startle response, which suggests it may have effects on the nervous system that could be beneficial in managing symptoms of orthostatic intolerance. ^{1 2 3 4 5}

Is clonidine generally safe for humans?

Clonidine is generally effective but can cause side effects like drowsiness, dry mouth, and sedation. It may also lead to withdrawal symptoms if stopped suddenly, which can include restlessness, sweating, and a rapid rise in blood pressure. ^{2 4 5 6 7}

What makes this drug treatment for orthostatic intolerance unique?

This treatment is unique because it combines multiple drugs, such as midodrine and atomoxetine, which have shown effectiveness in increasing blood pressure and reducing symptoms in patients with orthostatic hypotension. The combination approach may offer a more comprehensive management of symptoms compared to using a single drug. ^{8 9 10 11 12}

Research Team

Satish R Raj, MD MSCI

Principal Investigator

Vanderbilt University School of Medicine

Eligibility Criteria

This trial is for people who've felt dizzy or had a rapid heartbeat when standing up, lasting more than 6 months. It's not suitable for those with severe conditions like cancer or heart disease, or if they're taking drugs that could make their symptoms worse.

Inclusion Criteria

I have had symptoms for over 6 months when standing up.

Exclusion Criteria

I am not taking any medication that could worsen a fast heartbeat.

I have a long-term serious illness like cancer or heart disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various mechanistically unique medications to control heart rate and improve symptoms of orthostatic intolerance

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Abdominal binder
• Acetazolamide
• Atomoxetine
• Breathing Device
• Clonidine
• Drinking Water
• Entacapone
• Indomethacin
• Isosorbide Dinitrate
• IV Saline
• Mecamylamine
• Melatonin
• Memantine
• Midodrine
• Modafinil
• Octreotide
• Placebo
• Propranolol
• Sertraline

Trial Overview The study tests various treatments including medications like Octreotide and Propranolol, lifestyle aids such as abdominal binders, and other approaches to manage rapid heartbeat and discomfort upon standing in patients with orthostatic intolerance.

Participant Groups

Group I: Abdominal Binder Experimental Treatment 1 Intervention

Abdominal binder with inflatable pressure over abdomen

Group II: 9 Experimental Treatment 1 Intervention

Memantine

Group III: 8 Experimental Treatment 1 Intervention

Mecamylamine

Group IV: 7 Experimental Treatment 1 Intervention

Isosorbide Dinitrate

Group V: 6 Experimental Treatment 1 Intervention

Indomethacin

Group VI: 5 Experimental Treatment 2 Interventions

Entacapone

Group VII: 4 Experimental Treatment 1 Intervention

Clonidine

Group VIII: 3 Experimental Treatment 1 Intervention

NO Drug

Group IX: 2 Experimental Treatment 2 Interventions

Atomoxetine

Group X: 19 Experimental Treatment 1 Intervention

Dead Space Breathing Device

Group XI: 18 Experimental Treatment 1 Intervention

Drinking Water

Group XII: 17 Experimental Treatment 1 Intervention

Normal Saline (0.9%) 1 liter

Group XIII: 16 Experimental Treatment 1 Intervention

Sertraline

Group XIV: 15 Experimental Treatment 4 Interventions

Propranolol

Group XV: 13 Experimental Treatment 1 Intervention

Octreotide

Group XVI: 12 Experimental Treatment 2 Interventions

Modafinil

Group XVII: 11 Experimental Treatment 1 Intervention

Midodrine

Group XVIII: 10 Experimental Treatment 1 Intervention

Melatonin

Group XIX: 1 Experimental Treatment 1 Intervention

Acetazolamide

Group XX: 14 Placebo Group 1 Intervention

Placebo (lactose tablet)

Acetazolamide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Diamox for:

• Glaucoma
• Epilepsy
• Edema
• Altitude sickness

Approved in European Union as Diamox for:

• Glaucoma
• Epilepsy
• Edema

Approved in Canada as Diamox for:

• Glaucoma
• Epilepsy
• Edema
• Altitude sickness

Who Is Running the Clinical Trial?

Satish R. Raj

Lead Sponsor

Trials

7

Recruited

690+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

The effects of clonidine, prazosin, and propranolol on short-term and long-term habituation of the acoustic startle response in rats. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Aspects of tolerability of centrally acting antihypertensive drugs. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Motor and cardiovascular effects of selective alpha 2-adrenoceptor antagonists in the decerebrated rabbit. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Actions of alpha2 adrenoceptor ligands at alpha2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for alpha2A adrenoceptors. [2019]

5. England pubmed.ncbi.nlm.nih.gov

The interaction between clonidine and various neuroleptic agents and some benzodiazepine tranquillizers. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Pharmacological nature of newer imidazoli(di)nes on rat anococcygeus muscle. [2019]

7. England pubmed.ncbi.nlm.nih.gov

A comparative study of the reversal by different alpha 2-adrenoceptor antagonists of the central sympatho-inhibitory effect of clonidine. [2019]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Drug treatment of orthostatic hypotension because of autonomic failure or neurocardiogenic syncope. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Atomoxetine for Orthostatic Hypotension in an Elderly Patient Over 10 Weeks: A Case Report. [2015]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Use of citrulline malate (stimol) in patients with autonomic dystonia associated with arterial hypotension]. [2016]

11. United States pubmed.ncbi.nlm.nih.gov

Midodrine hydrochloride in the treatment of vasovagal syncope. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Pindolol acts as beta-adrenoceptor agonist in orthostatic hypotension: therapeutic implications. [2019]