The Effect of CPC on Aborting Tilt Induced Syncope in Patients With a History of Vasovagal Syncope or Near Syncope

Study Overview
=================
Brief Summary
-----------------
Syncope is defined as transient loss of consciousness associated with inability to maintain postural tone with rapid and spontaneous recovery. The purpose of this study is to assess the effects of sublingual administration of a new medication called CPC on tilt-induced syncope in patients with a history of vasovagal syncope (VVS) or near syncope. 140 participants were randomized at the University of Wisconsin - Madison. Each participant will be in the study for 1 day.

Detailed Description
-----------------
Vasovagal syncope (VVS) is the most common type of syncope. The mechanism is reflex-mediated triggered by various afferent input to the brain. The event is usually preceded by diaphoresis, warmth, nausea, and pallor, and is followed by fatigue. While several drugs are indicated in the treatment of VVS, to our knowledge, there is no current treatment of an impending syncopal attack. In the present study, the investigators hypothesize that a single administration of sublingual CPC preparation during the prodromal phase aborts tilt-induced syncope or near syncope with SBP less than or equal to 70 mmHg in patients with a history of VVS. Patients with an established diagnosis of typical VVS or near syncope will be randomized to receive CPC or placebo in 1:1 ratio. Drug or placebo will be administered at the onset of prodromes during tilt table testing. In addition to the primary endpoint (syncope or near syncope with SBP less than or equal to 70 mmHg), the investigators will be assessing the effects of the drug on time to event, incidence of asystole (> 3 sec), and fatigue after tilt table testing.

Official Title
-----------------
The Effect of Capsaicin-Phenylephrine-Caffeine Formulation on Aborting Tilt Induced Syncope in Patients With a History of Vasovagal Syncope or Near Syncope

Conditions
-----------------
Syncope, Vasovagal

Intervention / Treatment
-----------------
* Drug: CPC - Capsaicin, Phenylephrine, Caffeine
* Diagnostic Test: Tilt Table Test
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Established diagnosis of typical vasovagal syncope or near syncope Age 18-50 years Exclusion Criteria: Systolic BP >130 mmHg History of hypertension or cardiac arrhythmias History of cardiovascular disease or cerebral ischemic events Allergic reaction to any of the drug components Contraindication to tilt testing Any physical or psychological symptom, based on the clinical judgment of the investigators that would make a participant unsuitable for the study Any use of a medication(s) based on the clinical judgment of the investigators that would make a participant unsuitable for the study (e.g. fludrocortisone, theophylline, prazosin, doxazosin, terazosin, MAO-inhibitors, pseudoephedrine, decongestant and PDE5 inhibitors). Unwilling to discontinue Midodrine or beta-blocker therapy 48 hours before tilt table testing. Women who are pregnant (confirmed with pregnancy test on day of study) or lactating.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPC Adminstration<br>Single dose of CPC will be given during tilt table test | Drug: CPC - Capsaicin, Phenylephrine, Caffeine<br>* CPC is a combination of Capsaicin, Phenylephrine and Caffeine<br>Diagnostic Test: Tilt Table Test<br>* Participant will undergo tilt tablet testing using the Italian protocol (see reference section). The Italian protocol includes 20 minutes of passive tilt at 70 degrees (Passive Phase) followed by nitroglycerin (NTG) administration and tilt testing for another 15 minutes (NTG Phase).<br>|
| Placebo Comparator: Placebo Adminstration<br>Single dose of Placebo will be given during tilt table test | Diagnostic Test: Tilt Table Test<br>* Participant will undergo tilt tablet testing using the Italian protocol (see reference section). The Italian protocol includes 20 minutes of passive tilt at 70 degrees (Passive Phase) followed by nitroglycerin (NTG) administration and tilt testing for another 15 minutes (NTG Phase).<br>Drug: Placebo<br>* Placebo for CPC<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who have hypotensive syncope or near syncope with SBP less than or equal to 70 mmHG during tilt test | Hypotensive syncope is defined as transient loss of consciousness associated with SBP less than or equal to 90 mmHg. Near syncope is defined as sensation of near fainting while still being responsive to verbal commands. Near syncope will be used as a primary endpoint only when it is associated with a SBP less than or equal to 70 mmHg. | During tilt table testing (up 35 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to syncope or near-syncope after CPC or placebo administration | Time in minutes | During tilt table testing (up 35 minutes) | 
| Percentage of patients who have asystolic pauses > 3 sec in the CPC and placebo arms | Asystole will be defined as absence of QRS complexes | During tilt table testing (up 35 minutes) | 
| Fatigue Score at 1, 4, and 8 hours post tilt table testing | Self report of fatigue on a 1-5 scale where higher numbers indicate increased fatigue | Up to 8 hours after tilt table testing | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neurocardiogenic Syncope, Reflex Syncope, Fainting Spells