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| ID | Type | Description | Link |
|---|---|---|---|
| Protocol Version 4/12/2022 | Other Identifier | UW Madison | |
| A534225 | Other Identifier | UW Madison | |
| SMPH/MEDICINE/CARDIOLOGY | Other Identifier | UW Madison |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CPC Adminstration | Experimental | Single dose of CPC will be given during tilt table test |
|
| Placebo Adminstration | Placebo Comparator | Single dose of Placebo will be given during tilt table test |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CPC - Capsaicin, Phenylephrine, Caffeine | Drug | CPC is a combination of Capsaicin, Phenylephrine and Caffeine |
|
| 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) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mohamed H Hamdan, MD | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Wisconsin- Madsion | Madison | Wisconsin | 53792 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11194602 | Background | 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. |
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Digital consent was obtained in 143 subjects. 14 subjects were not randomized for various reasons; no show (n=3), withdrew consent (n=4), SBP > 130 mmHg (n=6) and not withholding Midodrine (n=1). A total of 129 subjects were randomized to CPC (n=66) or Placebo (n=63).
Participants were recruited at the University of Wisconsin- Madison using general recruitment emails addressed to students, faculty and staff and UW Heath Faint and Fall Clinic patients. All participants signed electronic consents in advance of study visit. The first participant completed the study in July 2021, and the last participant completed the study in August 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | CPC Adminstration | Single dose of CPC will be given during tilt table test at onset of prodromes. CPC - Capsaicin, Phenylephrine, Caffeine |
| FG001 | Placebo Adminstration | Single dose of Placebo will be given during tilt table test at onset of prodromes |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Evaluable participants for intention to treat primary endpoint By protocol entry criteria the age range was 18 to 50 Years.
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| ID | Title | Description |
|---|---|---|
| BG000 | CPC Adminstration | Participant who were randomized to received CPC during Tilt Testing for which evaluable data was available. |
| BG001 | Placebo Administration | Participant who were randomized to received Placebo during Tilt Testing for which evaluable data was available. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Intention to treat based on randomized treatment assignment | Posted | Count of Participants | Participants | During tilt table testing (up to approximately 35 minutes) |
|
Start of study visit to 8 hours post CPC or Placebo administration
All symptoms reported by a participant that were unexpected in terms of intensity or duration were reported even if no study medication was given. The signs and symptoms associated with prodromes or events i.e. vasovagal syncope or near syncope were not reported as adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CPC Adminstration | Participants who were randomized to received CPC during Tilt Testing |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedRAD Version 26.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mohamed H. Hamdan, MD, MBA | University of Wisconsin - Madison Cardiovascular Medicine | 608-263-4856 | mhamdan@medicine.wisc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 4, 2023 | Dec 21, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 23, 2023 | Dec 21, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D019462 | Syncope, Vasovagal |
| D013575 | Syncope |
| ID | Term |
|---|---|
| D054971 | Orthostatic Intolerance |
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D010656 | Phenylephrine |
| D002110 | Caffeine |
| D018667 | Tilt-Table Test |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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Randomized 1:1 to CPC or placebo
| Tilt Table Test | Diagnostic 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 | Drug | Placebo for CPC |
|
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) |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Syncope History | Participants who have a health history of Syncope or Near Syncope. | Count of Participants | Participants |
|
| Placebo Administration |
Participant who were randomized to received Placebo during Tilt Testing for which evaluable data was available. |
|
|
|
| Primary | 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 | Secondary endpoints analyses were limited to participants who had syncope or near syncope | Posted | Median | Standard Deviation | seconds | During tilt table testing (up to approximately 35 minutes) |
|
|
|
|
| Secondary | 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 | Secondary endpoints analyses were limited to participants who had syncope or near syncope | Posted | Count of Participants | Participants | During tilt table testing (up to approximately 35 minutes) |
|
|
|
|
| Secondary | 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. | Secondary endpoints analyses were limited to participants who had syncope or near syncope | Posted | Median | Standard Deviation | Score on a scale | Up to 8 hours after tilt table testing (up to approximately 8 hours and 35 minutes) |
|
|
|
|
| 0 |
| 66 |
| 0 |
| 66 |
| 3 |
| 66 |
| EG001 | Placebo Administration | Participants who were randomized to received Placebo during Tilt Testing | 0 | 63 | 0 | 63 | 4 | 63 |
| Nausea | Gastrointestinal disorders | MedRAD Version 26.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedRAD Version 26.1 | Non-systematic Assessment |
|
| Migraine Headache | Nervous system disorders | MedRAD Version 26.1 | Non-systematic Assessment |
|
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| D014474 | Unconsciousness |
| D003244 | Consciousness Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000588 |
| Amines |
| D014970 | Xanthines |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003935 | Diagnostic Techniques, Cardiovascular |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| Fatigue rated at 8 hour post tilt test |
|
| Secondary endpoint -- Measures of Fatigue for evaluable ITT population who had a primary event. | Wilcoxon (Mann-Whitney) | Measures of fatigue were compared between groups using the Wilcoxon rank-sum test. | 0.591 | Measures of fatigue were compared between groups using the Wilcoxon rank-sum test. | Superiority | Reporting for the 4 hour fatigue score only. |
| Secondary endpoint -- Measures of Fatigue for evaluable ITT population who had a primary event. | Wilcoxon (Mann-Whitney) | Measures of fatigue were compared between groups using the Wilcoxon rank-sum test. | 0.034 | Measures of fatigue were compared between groups using the Wilcoxon rank-sum test. | Superiority | Reporting for the 8 hour fatigue score only. |