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

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

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 will be randomized at the University of Wisconsin - Madison. Each participant will be in the study for 1 day.

Study Overview

• Status: Completed
• Conditions: Syncope, Vasovagal
• Intervention / Treatment: Drug: CPC - Capsaicin, Phenylephrine, Caffeine; Drug: Placebo; Diagnostic test: Tilt Table Test

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 hypothesized that a single administration of sublingual CPC preparation during the prodromal phase would abort 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 syncope.

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin- Madsion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Established diagnosis of typical vasovagal syncope or near syncope
2. Age 18-50 years

Exclusion Criteria:

1. Systolic BP >130 mmHg
2. History of hypertension or cardiac arrhythmias
3. History of cardiovascular disease or cerebral ischemic events
4. Allergic reaction to any of the drug components
5. Contraindication to tilt testing
6. Any physical or psychological symptom, based on the clinical judgment of the investigators that would make a participant unsuitable for the study
7. 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).
8. Unwilling to discontinue Midodrine or beta-blocker therapy 48 hours before tilt table testing.
9. Women who are pregnant (confirmed with pregnancy test on day of study) or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPC Adminstration; Single dose of CPC will be given during tilt table test	Drug: CPC - Capsaicin, Phenylephrine, Caffeine; CPC is a combination of Capsaicin, Phenylephrine and Caffeine; Diagnostic test: Tilt Table Test; 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).
Placebo Comparator: Placebo Adminstration; Single dose of Placebo will be given during tilt table test	Drug: Placebo; Placebo for CPC; Diagnostic test: Tilt Table Test; 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).

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 to approximately 35 minutes)
Time to Syncope or Near-syncope After CPC or Placebo Administration	Time in seconds from CPC or Placebo administration to syncope or near syncope in patients who had an event	During tilt table testing (up to approximately 35 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Have Asystolic Pauses > 3 Seconds in the CPC and Placebo Arms	Percentage of Participants with an event who had asystolic pauses > 3 seconds during syncope or near syncope	During tilt table testing (up to approximately 35 minutes)
Fatigue Scores at 1, 4, and 8 Hours Post Tilt Table Testing	Fatigue Scores at 1, 4 and 8 hours post tilt table testing in participants who had an event. Using standard continuous fatigue scale of 1 to 5, with 1 = no fatigue and 5 = max fatigue.	Up to 8 hours after tilt table testing (up to approximately 8 hours and 35 minutes)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Mohamed H Hamdan, MD, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Bartoletti A, Alboni P, Ammirati F, Brignole M, Del Rosso A, Foglia Manzillo G, Menozzi C, Raviele A, Sutton R. 'The Italian Protocol': a simplified head-up tilt testing potentiated with oral nitroglycerin to assess patients with unexplained syncope. Europace. 2000 Oct;2(4):339-42. doi: 10.1053/eupc.2000.0125.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): August 25, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): July 17, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Neurocardiogenic Syncope; Reflex Syncope; Fainting Spells
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Autonomic Nervous System Diseases; Unconsciousness; Consciousness Disorders; Primary Dysautonomias; Orthostatic Intolerance; Syncope; Syncope, Vasovagal; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Purinergic Antagonists; Purinergic Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Dermatologic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Antipruritics; Central Nervous System Stimulants; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Caffeine; Capsaicin; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: 2021-0081; A534225 (Other Identifier: UW Madison); SMPH/MEDICINE/CARDIOLOGY (Other Identifier: UW Madison); Protocol Version 4/12/2022 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No