Treatment of Orthostatic Intolerance

Study Overview
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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.

Official Title
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Treatment of Orthostatic Intolerance

Conditions
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Tachycardia, Chronic Orthostatic Intolerance

Intervention / Treatment
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* Drug: Acetazolamide
* Drug: Atomoxetine
* Other: NO Drug
* Drug: Clonidine
* Drug: Entacapone
* Drug: Entacapone & Propranolol
* Drug: Atomoxetine & Propranolol
* Drug: Indomethacin
* Drug: Mecamylamine
* Drug: Isosorbide Dinitrate
* Dietary Supplement: Melatonin
* Drug: Midodrine
* Drug: Modafinil
* Drug: Octreotide
* Radiation: Placebo
* Drug: Propranolol
* Drug: Modafinil & Propranolol
* Drug: Sertraline
* Procedure: IV Saline
* Other: Drinking Water
* Device: Breathing Device
* Drug: memantine
* Device: Abdominal binder


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in heart rate with standing |  | 1-4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tachycardia, sinus tachycardia, postural tachycardia syndrome (POTS)