Conditions: Syncope, Vasovagal
Keywords: Neurocardiogenic Syncope Reflex Syncope Fainting Spells
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 143
Healthy volunteers: no

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 will be 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 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.

Arms:
arm 1: Single dose of CPC will be given during tilt table test arm 2: Single dose of Placebo will be given during tilt table test

Interventions: intervention 1: CPC - Capsaicin, Phenylephrine, Caffeine intervention 2: Tilt Table Test intervention 3: Placebo
Intervention descriptions: intervention 1: CPC is a combination of Capsaicin, Phenylephrine and Caffeine intervention 2: 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). intervention 3: Placebo for CPC

Protocol document:
Prot_SAP_000.pdf: 
 
 
PROTOCOL 
The Effect of Capsaicin-Phenylephrine-Caffeine 
Formulation on Aborting Tilt Induced Syncope in 
Patients with a History of Vasovagal Syncope or Near 
Syncope 
 
 
NCT Number: NCT04972123 
 
Principal Investigator: Mohamed H Hamdan, MD, MBA 
 
Version 4 
Date May 4, 2023 
IND Number: 140732 
Phase IIa 
 
This document is confidential. 
No part of it may be transmitted, reproduced, published, or used by other persons 
without prior authorization from the Sponsor or Principal Investigator. 
 


 
 
 
 
The Effect of Capsaicin-Phenylephrine-Caffeine 
Formulation on Aborting Tilt Induced Syncope in 
Patients with a History of Vasovagal Syncope or Near 
Syncope 
 
 
 
 
Principal Investigator: Mohamed H Hamdan, MD, MBA 
 
Version 4 
Date May 4, 2023 
 
 
IND Number: 140732 
Phase IIa 
 
 
 
 
 
 
 
 
 
 
 
 
 
This document is confidential. 
No part of it may be transmitted, reproduced, published, or used by other persons without prior 
authorization from the Sponsor or Principal Investigator. 
 
 


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Table of Contents:  
 
Statement of Compliance ............................................................................................................ 2 
1.0  Study Synopsis .................................................................................................................... 3 
2.0  Background .......................................................................................................................... 5 
3.0  Study Hypothesis and End-points ........................................................................................ 7 
4.0  Study Design ........................................................................................................................ 7 
4.1  Inclusion criteria ........................................................................................................ 8 
4.2  Exclusion criteria ...................................................................................................... 8 
4.3  Concomitant Therapy ............................................................................................... 8 
4.4  Randomization and Blinding ..................................................................................... 8 
4.5  Dosing and Administration ........................................................................................ 8 
4.6  Tilt Test Procedure ................................................................................................... 8 
5.0  Drug Information ................................................................................................................ 10 
 
5.1  Packaging and Labeling ......................................................................................... 10 
 
5.2  Preparation ............................................................................................................. 10 
 
5.3  Storage and Stability .............................................................................................. 11 
 
5.4  Investigational Product Accountability ..................................................................... 11 
6.0  Assessment of Safety ........................................................................................................ 11 
6.1  Potential Risks and Mitigation Strategies ................................................................ 11 
6.2  Adverse Event Collection ........................................................................................ 11 
6.3  Reporting of AE’s, SAE’s and UP’s ......................................................................... 13 
6.4  Study and Participant Stopping Rules ..................................................................... 13 
7.0  Study Analysis ................................................................................................................... 14 
 
7.1  Statistical Analysis .................................................................................................. 14 
 
7.2  Interim Analysis ...................................................................................................... 14 
 
7.3  Sample Size ........................................................................................................... 15 
8.0  Data Collection ................................................................................................................... 15 
8.1  Data Collection Forms ............................................................................................ 15 
8.2  Record Retention .................................................................................................... 15 
9.0  Regulatory, Ethical and Study Oversight Consideration ..................................................... 16 
9.1  Institutional Review Board Information .................................................................... 16 
9.2  Data Safety Monitoring Committee  ........................................................................ 16 
9.3  Study Monitoring ..................................................................................................... 16 
 
9.4  Protocol Deviations ................................................................................................. 16 
 
References ............................................................................................................................... 14 
 
 
 
 
 
 


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Statement of Compliance:  
 
The signature below constitutes that the research will be conducted in accordance with the 
approved protocol, applicable regulations, guidelines, laws and institutional policies.  
 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitment.  
 
 
 
Printed or Typed Name 
 Signature 
 Date 
Mohamed H. Hamdan, MD, MBA 
 
 
4MAY23 
Principal Investigator  
  
  
 
 
 
 
 
 
 
 
 


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1.0  Study Synopsis 
 
The purpose of this study is to assess the effects of sublingual administration of CPC (Capsaicin 
1mg, Phenylephrine 30 mg, Caffeine 200 mg) on tilt-induced syncope.  
 
Hypothesis: In the present study, we hypothesize that a single administration of sublingual 
CPC preparation during the prodromal phase aborts tilt-induced syncope or near syncope with 
SBP ≤ 70 mmHg in patients with a history of vasovagal syncope or near syncope. 
 
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 protocol: Double-blinded, acute, proof-of-efficacy, randomized study. Eligible patients 
will undergo tilt table testing (20 min passive + 15 min NTG phase) with continuous BP, HR and 
ECG monitoring. Patients will be randomized to receive CPC or placebo preparation to be 
administered at the onset of prodromal symptoms (blurred vision, lightheadedness, dizziness, 
epigastric discomfort, nausea, sweating, …). 
 
End-points 
Primary endpoint: Comparison of the percentage of patients who have hypotensive syncope or 
near syncope with SBP ≤ 70 mmHg during tilt test in the active and placebo arms.  
 
Hypotensive syncope is defined as transient loss of consciousness (unresponsive to verbal 
commands) associated with a SBP ≤ 90 mmHg. Near syncope is defined as sensation of “near 
fainting” but still responsive to verbal commands. Near syncope will be used as a primary 
endpoint only when it is associated with a SBP ≤ 70 mmHg. 
 
Secondary endpoints:  
• 
Time to syncope or near syncope after drug or placebo administration  
• 
Percentage of patients who have asystolic pauses >3 sec in the CPC and placebo arms  
• 
Measures of fatigue (Ordinal Scale 1-5) at 1, 4 and 8 hours after tilt test termination  
 


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Sample size: Knowing that the efficacy of current therapies for VVS range between 30% and 
50%, we hypothesize a 50% reduction in syncope or near syncope rate with the CPC product.  
Thus, in the intent to treat population, we assume that the active treatment arm will decrease 
the syncope rate from an absolute value of 62% to 34.1% (31% diluted with patients not 
completing the protocol, see statistical methods). A total of 126 patients (63 active and 63 
placebo) are needed in order to achieve a statistical power of 85.2% to detect this difference 
using a 2-sided overall significance level of 0.05 with a Pocock boundary (i.e. z = ± 2.1599 at 
both interim and final analysis). Accounting for the number of subjects that might not meet 
eligibility criteria after virtual enrolment, inflating the total number of subjects to be enrolled to 
143 patients should result in an adequate sample size. An interim analysis is predefined at the 
time in which 76 total patients are randomized and evaluable.  
 
Setting and timeline: The study will be conducted at the University of Wisconsin, Madison WI. 
It is estimated that the duration of enrolment will be 1-2 years. 
 
 


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2.0  Background 
 
Syncope is defined as transient loss of consciousness associated with inability to maintain 
postural tone with rapid and spontaneous recovery (Shen et al 2017). The presumed cause is 
cerebral hypoperfusion. The prevalence depends on the population being evaluated and has 
been reported to be as high as 41% with recurrent syncope occurring in 13.5% (Lamb et al 
1960). In the emergency department, syncope accounts for 0.8% to 2.4% of all visits (Olde 
Nordkamp et al 2009; Day et al 1982; Morichetti and Astorino 1998). Hospital costs associated 
with the inpatient evaluation of syncope exceed $2.4 billion per year in the United States (Sun 
2013). 
 
Vasovagal syncope (VVS) is the most common type of syncope. It is defined as syncope 
occurring after prolonged standing or with exposure to emotional stress, pain, or medical 
settings, and is associated with features such as diaphoresis, warmth, nausea, and pallor. 
Patients with VVS often experience fatigue following the event (Sheldon et al 2015). Vasovagal 
syncope is very common affecting up to 42% of woman and 32% of men by the age of 60 
(Ganzeboom et al 2006; Serletis et al 2006). The outcome in patients with VVS is benign 
however, the 1-year recurrence rate is 25-35% leading to significant impairment in quality of life 
including injuries and loss of employment (Sumner et al 2010).  
 
The mechanism of VVS is reflex-mediated triggered by various afferent input to the brain. The 
efferent response includes vagal activation leading to cardio-inhibition (CI) and brady-
arrhythmias, and sympathetic withdrawal leading to a decrease in systemic vascular resistance 
and vasodilatation (VD) (Morillo et al 1997; Mosqueda-Garcia 2000). The result is cerebral 
hypoperfusion. The hemodynamic pattern, i.e. cardioinhibitory, vasodepressive, or both, is 
independent of the trigger evoking reflex syncope. In patients where the trigger is prolonged 
standing, a reduction in preload alone is thought to be sufficient to reduce cerebral 
hypoperfusion without the need for sympathoinhibition (Fu and Levine 2014; Jardine et al 2002; 
Cook and Convertino 2002). Adenosine is an ATP derivative that impacts strongly the 
cardiovascular system through the activation of its membrane receptors A1R, A2AR, A2BR, or 
A3R, based upon their pharmacological properties. Activation of A1R leads to sinus bradycardia 
or AV block, while activation of A2AR leads to vasodilation (Shryock and Belardinelli 1997). 
Endogenous adenosine is implicated in most forms of reflex syncope. VVS patients have high 
adenosine plasma levels, high A2AR expression and special A2AR gene polymorphism 
(Saadjian et al 2002 and 2009, Deharo et al 2012). Theophylline, a non-specific antagonist of 
adenosine receptors, is a useful daily treatment of some forms of reflex syncope (Brignole et al 
2016).  
 
While several drugs are indicated in the treatment of VVS, to our knowledge, there is no current 
treatment of an impending syncopal attack. We have recently tested the effects of a new drug 
containing Capsaicin, Phenylephrine and Caffeine on blood pressure (BP). The rationale for 
using these 3 drug components is listed below: 
 
Capsaicin is an active alkaloid subtracted from chili peppers. It is an irritant for mammals 
including humans, and produces a sensation of burning in any tissue with which it comes into 
contact. These effects are secondary to the activation of transient receptor potential (TRVP1), 
which are vanilloid receptors present in great amount in C Fibers (Seabrook GR et al 2002).   
In our product, we chose Capsaicin for two reasons. First, Capsaicin causes local irritation 
which should elicit sympathetic activation. Second, Capsaicin causes local vasodilatation which 


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should facilitate the absorption of the two other compounds, namely Phenylephrine and 
Caffeine.  
 
We chose a dose of 1 mg of Capsaicin (corresponding to 60 µL of capsaicin 0.5%) to be 
included in our CPC product. This dose is close to the 0.75 mg dose used orally in the 
stratification of patients with functional dyspepsia (Fuhrer M, et al 2011).  
 
Phenylephrine is an alpha-adrenergic agonist that produces vasoconstriction. The increase in 
vascular resistance results in a dose-dependent increase in BP and reflex decrease in HR. 
When given systemically via the intravenous route, the effects are immediate and can last 15-20 
minutes. The half-life of the distribution (alpha) phase is around 5 minutes with the terminal 
elimination (beta) lasting 2-3 hours. The drug is excreted in the urine mostly as inactive 
metabolites (Hengstmann and Goronzy 1982; Kanfer I et al 1993). When given as an IV bolus 
for the treatment of hypotension, the dose is 100-500 mcg every 10-15 minutes (Rhodes A et al 
2017). In the ACLS guidelines, the dose for the treatment of severe hypotension (systolic BP < 
70 mm Hg) and low total peripheral resistance is 0.1 to 10 mcg/kg/minute (van Diepen S et al 
2017). The initial dose is 0.5 to 2 mcg/kg/minute with up titration to effect (Peberdy MA et al 
2010). Cardiovascular adverse reactions can include exacerbation of angina, hypertension, 
reflex bradycardia and worsening heart failure. Other side effects include anxiety, excitability, 
headache, chest discomfort and restlessness.  
 
The dose of Phenylephrine (30 mg) in our CPC product was determined based on the results of 
the Phase I study (see below). 
 
Caffeine is a methylxanthine derivative which is contained in many foods and drinks including 
tea, coffee, cola and chocolate. It is the most widely consumed psychoactive drug. Caffeine has 
been shown to cause an increase in BP and vascular resistance at rest and during exercise 
(Daniels J et al 1998; Robertson D et al 1978; Sung et al 1990). Following the administration of 
a single dose of caffeine (250mg orally), the peak increase in BP was noted at 30 minutes with 
a gradual return to baseline at 180 minutes (Mosqueda-Garcia R et al 1990). In another study 
including healthy, normotensive non-smoking adults, the ingestion of 3.3 mg/Kg of caffeine 
resulted in 4.1 and 3.8 mmHg increases in systolic and diastolic BP in men, and 4.5 and 3.3 
mmHg increases in women, respectively. Of interest, the mechanism was an increase in 
vascular resistance in men and an increase in cardiac output in woman (Hartley TR et al 2004). 
Acute ingestion but not chronic use of caffeine has also been shown to decrease baroreflex 
sensitivity. These effects are in part due to the blockade of adenosine A1 and A2 adenosine 
receptors (Fredholm BB 1985). Inhibition of A1 adenosine receptors leads to an increase in 
heart rate (HR), while inhibition of A2A adenosine receptors leads to vasoconstriction. In 
addition, caffeine has been shown to increase muscle sympathetic nerve activity in both habitual 
and nonhabitual coffee drinkers.  
 
The caffeine dose in our product is 200mg, the equivalent of the amount of caffeine present in a 
6-ounce cup of brewed drip coffee. It should be tolerated well with no significant side effects. 
 
In Phase 1 study, a total of 17 subjects received CPC sublingually with various doses of 
Phenylephrine. In the 6 participants who received CPC with the highest dose of PE (Capsaicin 1 
mg, Phenylephrine 30 mg, Caffeine 200 mg), a peak increase in SBP was noted at 2 minutes 
with an average of 21 mmHg (range 15-33 mmHg). The increase in BP persisted for at least 15 
minutes with a gradual decline over 2 hours (p value < 0.05 when compared to baseline at 1, 2, 
5 and 15 minutes for both SBP and DBP). The increase in BP was associated with an initial 


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increase in HR followed by a decrease to below baseline over the 2-hour period (Figures 1A 
and 1B).  
 
Figures 1A and 1B 
 
 
 
 
.  
3.0 Study Hypothesis and End-points 
 
In the present study, we hypothesize that a single administration of sublingual CPC preparation 
during the prodromal phase aborts tilt-induced syncope or near syncope with SBP ≤ 70 mmHg  
in patients with a history of vasovagal syncope or near syncope. 
 
Primary endpoint:  
 
Comparison of the percentage of patients who have hypotensive syncope or near syncope with 
SBP ≤ 70 mmHg during tilt test in the CPC and placebo arms. 
 
Hypotensive syncope is defined as transient loss of consciousness associated with SBP ≤ 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 ≤ 70 mmHg. 
 
Secondary endpoints:  
• 
Time to syncope or near-syncope after CPC or placebo administration  
• 
Percentage of patients who have asystolic pauses >3 sec in the CPC and placebo arms  
• 
Measures of well-being at 1,4 and 8 hours after tilt test termination (Ordinal scale 1-5 for  
fatigue) 
 
4.0  Study Design  
 
Patients with an established diagnosis of typical VVS or near syncope will be contacted by 
phone for enrollment and the start of the informed consent discussion.  All participants will be 
asked to sign the approved consent and HIPAA authorization document before any study 
related procedures are completed.   
 
After verbal agreement to participate via phone, patients on Midodrine (COR 2A) and beta-
blockers (COR 2B) will be asked to discontinue the medication 48 hours before tilt testing.  


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4.1 Inclusion Criteria 
1. Established diagnosis of typical vasovagal syncope or near syncope 
2. Age 18-50 years 
 
4.2 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. 
 
4.3 Concomitant Therapy  
As stated above, patients taking Midodrine and beta-blockers must discontinue such drugs at 
least 48 hours before the test. Patients can continue taking concurrent medications that do not 
conflict with eligibility requirements for the study. Concurrent medications taken 48 hours before 
tilt table testing and caffeine intake on the day of the study will be recorded. 
 
4.4 Randomization and Blinding 
Eligible patients are assigned, according to a central computer-generated randomization list, to 
one of the 2 study arms: CPC or Placebo. The transcript of the CPC identification code is blind to 
the investigators and to patients. 
4.5 Dosing and Administration 
Prior to administration, the research RN will warn the subject that some people may experience 
a minor burning sensation. The CPC or placebo will be administered as fast as possible from an 
oral syringe sublingually. The participant must allow the gel to reside under the tongue for 1 
minute before the gel is swallowed.  After swallowing CPC, sips of water will be allowed.   
 
4.6 Tilt Test Procedure  
Patients will undergo tilt tablet testing using the Italian protocol, which is slightly different than 
the current UW-Health protocol (Bartoletti et al, 2000). The Italian protocol includes 20 minutes 
of passive tilt at 70 degrees (Passive Phase) followed by nitrogylcerin (NTG) administration and 
tilt testing for another 15 minutes (NTG Phase). The current protocol at UW-Madison is similar 
except for the NTG Phase which is 10 minutes instead of 15 minutes. Continuous non-invasive 
monitoring and recording of arterial blood pressure (BP), heart rate (HR) and ECG tracings will 
be obtained.  
 


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If patients experience no prodromes (blurred 
vision, lightheadedness, dizziness, epigastric 
discomfort, nausea, sweating, …), the tilt test will 
be performed until completion of both phases or 
until syncope occurs. No CPC or placebo will be 
administered. 
 
If patients experience prodromes (blurred vision, 
lightheadedness, dizziness, epigastric 
discomfort, nausea, sweating, …) CPC or 
placebo will be administered from a syringe 
sublingually as fast as possible. Patients will be 
asked to allow the gel to reside under the tongue 
for 1 minute before it can be swallowed, followed 
by sips of water as needed. Tilt testing will then 
continue for an additional 5 minutes as described 
below or until syncope occurs, whichever comes 
first:  
 
• 
If the CPC or Placebo are administered in 
the passive phase and the required 
additional 5 minutes extend beyond the 
usual 20 minutes, upright tilt is continued 
until the completion of the additional 5 
minutes without the subsequent administration of NTG.  
• 
If CPC or Placebo are administered in the NTG phase and the required additional 5 
minutes extend beyond the usual 15 minutes, upright tilt is continued until the completion 
of the additional 5 minutes even if the total duration of tilt now exceeds the 35-minute 
duration.  
  
Measurements (baseline and during tilt test):  
• 
Baseline supine BP and HR 
• 
Time of CPC administration during upright tilt 
• 
Symptoms, BP, HR at onset of prodromes, 1 minute, 2 minutes and 5 
minutes after CPC or Placebo administration. Measurements will be 
interrupted if the patient is back in the supine position.  
• 
Time to syncope or near syncope after CPC or placebo drug 
administration  
• 
BP, HR and ECG tracing during syncope or near syncope when 
applicable 
• 
BP, HR immediately after resumption of supine position and at 5, 15 
and 30 min 
• 
Symptoms during the duration of tilt testing including post-CPC or 
placebo administration  
 
After the tilt test, patients will be asked to complete a self-administered fatigue evaluation. 
Participants will remain in clinic until the 1-hour evaluation is completed and will be given the 4-
hour and 8-hour form to be completed at home and mailed back to the study team.  Patients will 
be instructed not to take any medications until completion of the 8-hour evaluation. After the 8-
Figure 2  
 
 


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hour waiting period, they will be asked to resume Midodrine and beta-blockers if previously 
prescribed. 
 
5.0  Drug Information 
 
CPC and placebo gel will be provided by Hybrid Pharma (1015 W. Newport Center Dr, Suite 
106A, Deerfield Beach, FL 33442), an external pharmaceutical company (RBD) that is GMP 
certified.  
5.1  Packaging and Labeling  
For CPC Product per 1mL:  
Active Components 
Capsaicin 1 mg/mL 
Caffeine 
200 mg/mL 
Phenylephrine  30 mg/mL 
 
Inactive Components 
Povidone (polyvinylpyrrolidone, PVP) 
Polyethylene glycol 3350 (PEG 3350) 
Peppermint Oil 
FD&C Blue #1 Lake 
Polyethylene glycol 400 (PEG 400) 
Propyl gallate 
 
      For Placebo per 1 mL:  
Inactive Components 
Povidone (polyvinylpyrrolidone, PVP) 
Polyethylene glycol 3350 (PEG 3350) 
Peppermint Oil 
FD&C Blue #1 Lake 
Polyethylene glycol 400 (PEG 400) 
Propyl gallate 
 
Dose Delivery for CPC or Placebo   
CPC or placebo dose of 1 mL will be loaded in a 3 mL syringe, sealed with a tip cap.  
5.2  Preparation 
All clinical drug research protocols within UW Hospital and Clinics, must be coordinated through 
the UW Pharmaceutical Research Center (PRC). For this study, PRC will randomize 
participants to treatment group, and maintain the randomization code list. PRC will prepare CPC 
or Placebo dose, for administration by study team during tilt test. 
 
 PRC Product Dispensing Label:  
Name__________________________ Date__________ 
Participant ID# ___________MR#______________ RPH: _______ 
CPC Compound: Capsaicin 1mg, Phenylephrine 30 mg, Caffeine 200mg or Placebo 
Directions: Give 1 ml sublingually, hold under tongue for 1 minute, then swallow   
FOR INVESTIGATIONAL USE ONLY      HSC# XXXX-XXXX 
Dr Hamdan, MD                 PH: 608-262-0143 
UW Health – University Hospital; 600 Highland Avenue, Madison WI 53792 


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5.3 Storage and Stability 
The product will be stored at refrigeration temperatures (4 C) and in the dark for long term 
storage. After loading into a 3 mL oral syringe, the dose can be stored for at least a week at 
controlled room temperature, shielded from direct sunlight. 
5.4  Investigational Product Accountability 
A perpetual inventory of study drug will be kept by the UW PRC.  Unused or partially-dispensed 
dosages will be returned to the PRC for return to stock or disposal, as appropriate. 
 
6.0   Assessment of Safety  
 
6.1   Potential Risks and Mitigation Strategies  
6.1.1 Known Risks related to CPC product and Mitigation Strategies  
Cardiovascular Risks: A common side effect is palpitations due to the increase in 
sympathetic activity and associated tachycardia. A common side effect of increased 
blood pressure (BP) is headache.  We believe this risk to be minimal because of the 
transient duration of BP increase and the exclusion of patients with a history of 
hypertension and cardiac arrhythmias. Results from the Phase I study revealed an 
average increase in SBP of 21 mmHg at 2 minutes with a range of 15-33 mmHg. In the 6 
participants that received the proposed dose, no serious side effects were reported. 
 
GI Risks: The oral pain from the administration of the capsaicin-containing product is 
expected, and may provide part of the therapeutic effect in future treatment of patients 
with VVS. Gastric discomfort and nausea is expected while participants are fasting, due 
to capsaicin.  Participants will be able to drink water one minute after the application of 
dose. In the 6 participants that completed the Phase 1 study, the highest Pain Score was 
at 2 minutes with a mean of 5 and a range of 3-8 (scale 1-10). All participants swallowed 
the medication after keeping it sublingual for 1 minute and no participant refused the 
second dose at 2 hours.  
 
6.1.2 Risks related to Tilt Table Test 
Tilt Table Testing is generally safe and complications are rare.  However, the known risks 
of the test are: low blood pressure, pauses between heart beats, nausea or vomiting after 
fainting, weakness that can last several hours. These symptoms generally improve when 
the table is placed in the flat position. Of note, these symptoms are similar to what 
patients experience when they have an event outside the hospital. The difference is that 
these events will be monitored and a provider will be available if needed. NTG 
administration can result in a headache. Participants may be required to sign the 
standard UW Health clinical consent for a Tilt Table Test as well.  
 
There is risk of loss of confidentiality as participation in this study will be noted in the UW-
Health EMR.  Data obtained during the study, will be keep in password protected files 
and/or locked offices.  
 
6.2 Adverse Event Collection:  
Adverse Events will be collected during the tilt test including drug or placebo administration and 
up to 8 hours post drug or placebo administration based on participants’ self-report.  
 
The presence of a syncopal event during the tilt test, with the associated signs and symptoms 
including but not limited to changes in HR or BP will not be an AE for this study.  The oral and 


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gastric discomfort from the sublingual administration of the CPC study drug is expected and will 
not be recorded as an AE.  
 
6.2.1 Adverse Event (AE) Definition  
Adverse event (AE) means any untoward or unfavorable medical occurrence in a human 
subject or others that happens during participation in a research study.  
 
6.2.2 Serious Adverse Event (SAE) Definition  
An adverse event is considered "serious" if, in the view of the investigator, meets any of the 
following criteria: 
• 
Results in death 
• 
Is life-threatening  
• 
Requires an inpatient hospitalization or prolongation of an existing hospitalization  
• 
Results in persistent or significant disability or incapacity  
• 
Results in a congenital anomaly/birth defect 
• 
Constitutes, based upon appropriate medical judgment, an event that may jeopardize 
the participant’s health and may require medical or surgical intervention to prevent 
one of the other outcomes listed above 
 
6.2.3 Unanticipated Problem (UP) Definition  
The Office for Human Research Protections (OHRP) considers unanticipated problems 
involving risks to research participants or others to include, in general, any incident, 
experience, or outcome that meets all of the following criteria:  
• 
The incidence, experience, or outcome is unexpected given the research procedures 
described in protocol-related documents (e.g., the study protocol, the consent 
documents) and the characteristics of the subject population being studied. An event 
may be considered unexpected if it exceeds the nature, severity, or frequency described 
in the study-related documents. 
• 
The incidence, experience, or outcome is related or probably related to participation in 
the research study. Probably related means the incidence, experience, or outcome is 
more likely than not to be caused by the research study procedures. 
• 
The occurrence of the incidence, experience, or outcome suggests that the research 
places participants or others at a greater risk of harm (physical, psychological, 
economic, or social) than was previously known or recognized 
 
6.2.4  Classification of an Adverse Event  
Severity of the AE: The investigator will classify all AE’s related to the following scale:  
• 
Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning.  
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening 
or incapacitating. For this protocol, providing milk and/or bread to reduce oral 
discomfort will not be considered treatment or infer severe toxicity.  


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• 
Life threatening - The patient was at risk of death at the time of the event.  
• 
Fatal - The event caused death. 
 
6.2.5  Relationship of AE to Investigation Product: The investigator will determine the 
relationship of all AE’s based on the following scale:  
• 
Definitely Related – Clearly related to the study procedures/intervention and other 
possible contributing factors can be ruled out. 
• 
Probably Related – Likely related to the study procedures/intervention and the 
influence of other factors is unlikely.  
• 
Possibly Related – Possibly related to the study procedures/intervention and there 
are other factors that could be equally likely. 
• 
Unlikely to be related – Doubtfully related to the study procedures/intervention and 
there is another likely cause. 
• 
Unrelated – Clearly not related to the study procedures/intervention and/or evidence 
exists that the event is definitely related to another cause. 
 
An AE will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described in this clinical protocol and/or the 
investigational brochure.  
 
6.3  Reporting of AE’s, SAE’s and UP’s  
AE/SAEs that meet the definition of an unanticipated problem will be reported to the HSIRB 
within 14 business days of learning of the event. Events that are immediately life threatening, 
severely debilitating to other current participants or resulted in a death will be reported to the 
IRB Chair or IRB Director via telephone or email within 24 hours (1 business day) of site 
awareness. 
 
Events that are determined to be meet the FDA safety reporting requirements will be submitted 
by the sponsor-investigator within the timeframes described in following table. 
 
Adverse Events that include all 
of the following: 
Notify in the time specified below based on date 
study team learned of event.  
• 
Serious (SAE) 
• 
Suspected/Related* 
• 
Unexpected 
HSIRB: Within 14 business days  
DMC: Within 15 calendar days  
FDA: Within15 calendar days  
• 
Life threatening or Fatal 
• 
Suspected/Related* 
• 
Unexpected 
HSIRB: Within 1 business day  
DMC: Within 7 calendar days    
FDA: Within 7 calendar days  
*Events that are possibly, probably, or definitely related meet the criteria for 
“Suspected/Related” 
 
6.4  Study and Participant Stopping Rules:  
Study Stopping Rules: 
Study Accrual will be paused if a participant experiences a SAE while the investigator reviews 
the case to determine if it meets the definition on an unanticipated problem.  
 


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This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. If the study is prematurely terminated or suspended, the investigator will 
inform the IRB and regulatory authorities, including the reason(s) for the termination or 
suspension.  
 
Participant Stopping Rules: 
Participants may choose to discontinue participation at any time. If the investigator determines 
that study participation is not in participant’s best interest, study participation may be stopped.  
 
 
7.0 Study Analysis  
 
7.1 Statistical Analyses 
 
The primary outcome of the proportion of patients who experience hypotensive syncope or 
near syncope with SBP ≤ 70 mmHg during the tilt test will be compared between active and 
placebo arms via the two-sample z-test for population proportions. Given this primary outcome, 
we acknowledge the possibility that a subject may be randomized and participate in the 
protocol, but blood pressure measurement may not be available throughout the study period 
due technical problems. A subject who experiences near syncope without a known concurrent 
blood pressure measure would be unevaluable for the primary outcome. Thus, we define 
randomized subjects into two categories. First, randomized – evaluable patients are patients 
who are randomized and have complete blood pressure measurements that are sufficient to 
make a determination on the primary outcome. And second, we define randomized – 
unevaluable patients as those randomized patients whom, because of a lack of blood pressure 
measurement, we would be unable to determine if they had a primary outcome.     Specifically, 
we define xa and xp to be the number of randomized – evaluable patients in the active and 
placebo arms, respectively, who experience hypotensive syncope or near syncope with SBP ≤ 
70 mmHg from the na and np patients that are randomized – evaluable patients in each group, 
then the z-test statistic is given by 
 
 
𝒛𝒛= 
𝒙𝒙𝒂𝒂
𝒏𝒏𝒂𝒂−𝒙𝒙𝒑𝒑
𝒏𝒏𝒑𝒑 
ට𝒑𝒑ഥ (𝟏𝟏−𝒑𝒑ഥ) ቀ𝟏𝟏
𝒏𝒏𝒂𝒂+ 𝟏𝟏
𝒏𝒏𝒑𝒑ቁ
 
 
where 𝑝𝑝̅ = ൫𝒙𝒙𝒂𝒂+ 𝒙𝒙𝒑𝒑൯/൫𝒏𝒏𝒂𝒂+ 𝒏𝒏𝒑𝒑൯. The test statistic will be evaluated against the Pocock 
boundaries at the interim and possible final analysis.  
 
Secondary outcome measures include time to syncope or near syncope with SBP ≤ 70 mmHg, 
proportions of patients who experience asystolic pauses > 3 seconds, and measures of fatigue. 
Time to syncope or near syncope with SBP ≤ 70 mmHg will be measured from the time of 
administration of sublingual CPC or Placebo. Patients who do not experience syncope will be 
censored at the end of the tilt test. A log-rank test statistic will be used to compare the active 
and placebo arms. The Chi-square test or Fisher’s exact test will be used to compare the 
number of patients who experience asystolic pauses > 3 seconds. Measures of fatigue will be 
compared via the Wilcoxon rank-sum test. All tests will be two-sided using a 0.05 level of 
significance. 


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Adverse events during the tilt test will be recorded and designated as before or after 
administration of CPC or Placebo as well as whether the event is considered serious or not. 
Events will further be classified by MedDRA System Organ Class (SOC). Safety Measures will 
include whether a subject has any adverse or serious adverse events as well as the total 
number of each. Comparisons between treatment arms will be conducted both overall and 
within SOC. Chi-square or Fisher exact tests will be used to compare the proportion of patients 
with events, while the Wilcoxon rank-sum test will be used to compare the average number of 
events a patient experiences.  
 
7.2 Interim Analysis 
A single interim analysis of efficacy is planned for when 76 subjects have been randomized and 
completed the tilt test and determined evaluable for the primary outcome. A data safety 
monitoring committee will be unblinded to the interim data while the PI and the rest of the study 
team will remain blinded. A Pocock monitoring boundary (Pocock 1977) will be calculated so as 
to preserve an overall two-sided significance level of 0.05 across both the interim and possible 
final analysis for the primary analysis. The boundary will be calculated based on the actual 
number of patients randomized with data available for use at the time of the interim analysis.    
 
7.3 Sample size 
At our institution, the positivity rate i.e. induction of hypotensive syncope in patients referred for 
tilt table testing for VVS during the period of March 2014 through February 2015 was 61% (268 
out of 438 patients), (Chaddha et al 2016). Similarly, in a cohort population of 1602 patients 
aged 18 to 50 years undergoing tilt test in Italy, the positivity rate was 62% (unpublished data). 
 
Knowing that the efficacy of current therapies for VVS range between 30% and 50%, we 
hypothesize a 50% reduction in the primary endpoint with the CPC product.  However, we 
anticipate that at most 10% of subjects that are randomized may not complete the treatment 
regimen as assigned. Examples include refusal to keep medication under their tongue, 
inappropriate dispensement of medication, or not experiencing a prodrome and hence not being 
administered CPC or placebo. Thus, while we might assume an as-treated syncope rate of 62% 
for the placebo group and 31% for the CPC group, we assume the potentially diluted rates in the 
intent-to-treat (ITT) population to be 62% for the placebo arm and 34.1% for the active arm. A 
single interim analysis for efficacy is planned when 76 subjects have been randomized and 
determined evaluable for the primary outcome. A two-sided Pocock boundary will be employed 
to evaluate statistical significance maintaining an overall 2-sided significance level of 0.05 
across both potential analyses. Having 63 randomized evaluable subjects in each group, or 126 
total subjects, results in a statistical power of 85.2% to detect this difference in the ITT 
population syncope or near syncope with SBP ≤ 70 mmHg rates. In this case the information 
fraction at the first interim analysis is 60.31% and thus the Pocock critical values employed are z 
= ± 2.1599 in order to maintain the 0.05 significance level. 
 
We anticipate that a total of 9.4% of participants brought into the clinic for tilt testing might not 
actually meet the eligibility criteria and be withdrawn as a screen failure. We further estimate 
that 2% of the subjects that we randomized will not be evaluable for the primary endpoint. We 
therefore inflate our overall sample size to 143 total subjects to be enrolled in order to achieve 
the 126 randomized – evaluable patients to maintain our estimated statistical power. 
 
 
 


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8.0  Data Collection  
 
8.1  Data Collection Forms 
Standardized data collection forms (e.g., source documents, case report forms, standardized 
assessment forms, etc.) are used to ensure data collected are consistent and compliant with the 
protocol. Information about study participants will be kept confidential and managed according 
to the requirements. Data collection is the responsibility of study team members under the 
supervision of the principal investigator. The principal investigator is responsible for ensuring the 
accuracy, completeness, legibility, and timeliness of the recorded and reported data. Data 
recorded in the case report form (CRF) derived from source documents should be consistent 
with the data recorded on the source documents.   
 
 
8.2  Record Retention  
It is the investigator’s responsibility to retain study essential documents for a minimum of period 
of 7 years following completion of the study per UW-Madison institutional policy, or at least 2 
years after the last approval of a marketing application and until there are no pending or 
contemplated marketing applications or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product, whichever comes last. 
 
9.0  Regulatory, Ethical and Study Oversight Considerations   
 
9.1  Institutional Review Board (IRB) Information  
This protocol and the informed consent/HIPAA authorization document will be reviewed and 
approved by the UW Health Sciences IRB before initiation of the study and enrollment of 
participants.   All participants must provide informed consent as documented on the informed 
consent/HIPAA authorization document prior to participation in this study.  
 
9.2  Data Safety Monitoring Committee 
A study specific Data Monitoring Committee (DMC) with be created to oversee the study. The 
committee will consist of 2 Cardiologists not involved with the study and a Bio-Statistician.  
Based on the DMC Charter, a periodic analysis every 6 months of the study results will be 
performed by the DMC to independently judge whether the overall integrity and conduct of the 
protocol remains acceptable based on data provided and reported by the Principal Investigator. 
The DMC will make recommendations to the Principal Investigator that could include actions of 
continuation, modification, suspension, or termination.   
 
9.3  Study Monitoring  
Study monitoring will be conducted by an independent monitor to participant data and verify that 
the trial is in compliance with the approved protocol and applicable regulatory requirements.  
 
9.4  Protocol Deviations  
A protocol deviation is any noncompliance with the clinical trial protocol or investigational plan 
requirements. The noncompliance may be either on the part of the participant, the investigator, 
or the study site staff. As a result of deviations, corrective actions are to be developed by the 
site and implemented promptly. Noncompliance will be reported to the HSIRB as applicable and 
within the required time frame. 
 
 
 


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ICF_001.pdf: 
 
 
Consent Document 
The Effect of Capsaicin-Phenylephrine-Caffeine 
Formulation on Aborting Tilt Induced Syncope in 
Patients with a History of Vasovagal Syncope or Near 
Syncope 
 
 
NCT Number: NCT04972123 
 
Principal Investigator: Mohamed H Hamdan, MD, MBA 
 
Version 3 
Date May 5, 2023 
IND Number: 140732 
Phase IIa 
 
This document is confidential. 
No part of it may be transmitted, reproduced, published, or used by other persons without prior 
authorization from the Sponsor or Principal Investigator. 
 
 


HS IRB #: 2021-0081
Lead Researcher: Mohamed Hamdan, MD
Version: 3 dated 5/5/2023
Page 1 of 8
IRB Approval Date: 6/21/2021
University of Wisconsin – Madison
University of Wisconsin-Madison
Consent to Participate in Research
and
Authorization to Use Protected Health Information for Research
Study Title for Participants: CPC Tilt Table Test Study
Formal Study Title: The Effect of Capsaicin-Phenylephrine-Caffeine formulation on
Aborting Tilt Induced Syncope in Patients with a History of Vasovagal Syncope or
Near Syncope
Lead Researcher: Mohamed Hamdan, MD, 608-263-1532
Where Lead Researcher works: School of Medicine and Public Health, Department of
Medicine/Cardiovascular Medicine.
Invitation
We invite you to take part in a research study about vasovagal syncope or fainting. You
are being invited because you have a history of vasovagal syncope or near syncope.
This consent and authorization form will give you the information you need to decide if
you want to be in the study. It explains how health information will be used for this study
and requests your authorization (permission) to use your health information. Ask
questions about anything in this form that is not clear. If you want to talk to your family
and friends before making your decision, you can. When we have answered all your
questions, you can decide if you want to be in the study. This process is called
“informed consent.”
Why are researchers doing this study?
The purpose of this study is to see if giving a new medication called CPC aborts a
fainting spell during a Tilt Table Test. The new medication is called CPC, because it
contains Capsaicin, Phenylephrine and Caffeine. The results from our first study with
CPC showed that the drug was safe. The US Food and Drug Administration (FDA) has
not approved the CPC medication for use outside of research studies.
Fainting is defined as transient loss of consciousness. Vasovagal syncope (VVS) is the
most common type of fainting. It generally occurs after standing for a long time, or
exposure to emotional stress or with pain or with medical procedures. Along with loss
of consciousness people experience sweating, warmth, nausea and paleness. After
VVS, most people will feel tired. Overall, the CPC medication is being studied to see if
it would be useful in helping people abort or prevent fainting spells. We will also be
assessing its impact on fatigue after a fainting spell.
IRB Approval Date: 5/23/2023
University of Wisconsin – Madison


HS IRB #: 2021-0081
Lead Researcher: Mohamed Hamdan, MD
Version: 3 dated 5/5/2023
Page 2 of 8
IRB Approval Date: 6/21/2021
University of Wisconsin – Madison
This study is being done at the University of Wisconsin-Madison. A total of about 143
people will participate in this study.
What will happen in this study?
There is only 1 study visit at UW Hospital or UW Health Arbor Gate Heart Clinic during
which you will have a Tilt Table Test and be given either the CPC medication or a
placebo, together called study medication. A placebo looks like the real CPC but does
not have the 3 active medications. Which group you are in will be decided by chance,
like flipping a coin. Neither you nor the study team doing the Tilt Table Test will know
which group you are in.
If you are on a medication to treat your fainting, you may be asked to hold it for about48
hours before the study tilt table test. You will restart your medication 8 hours after the
Tilt Table Test.
Before the Tilt Table Test, you will be asked to not have anything to eat or drink for 4
hours before the test.
We will ask you about your medical history and all medications
that you take. If you are of childbearing potential a urine pregnancy test will be done
before the Tilt Table Test. The test must be negative for you to participant.
The Tilt Table Test will be done the same as other Tilt Table Test you may have had in
the past.
 
You will lie on the table and straps will be put around you to keep you safe when
the table is being moved.
 
You will have sticky patches called electrodes placed on your chest tomonitor
your heart rate and rhythm.
 
You will have blood pressure cuff put on your arm and fingers, so we canmonitor
your blood pressure during the test.
 
The table will be tilted upright for 20 minutes.
 
If you have not fainted after the 20 minutes, you will be given Nitroglycerin under
your tongue and tilted upright for another 15 minutes.
 
If you do not faint during that 15-minute period the test will end.
 
At any time if you start to feel like you are about to faint, you will be given the
study medication.
 
If you faint at any time during the test, the table to be returned to the flat position.
The study medication is given under your tongue. You will be asked to hold it under
your tongue for 1 minute before swallowing it. You will be given sips of water after you
swallow it. The upright tilt will continue for up to 5 minutes after you have been given
the study medication. If you do not have pre-fainting symptoms during the test, you will
not be given the study medication.
IRB Approval Date: 5/23/2023
University of Wisconsin – Madison


HS IRB #: 2021-0081
Lead Researcher: Mohamed Hamdan, MD
Version: 3 dated 5/5/2023
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IRB Approval Date: 6/21/2021
University of Wisconsin – Madison
After the completion of the tilt table test, you will be asked to fill out a symptom survey at
1, 4 and 8 hours. You will stay in the clinic until you complete the 1-hour survey. You
will be given the 4 and 8-hour survey to take home to complete and mail back to the
study team.
You should resume any medications that were held before the Tilt Table Test 8 hours
after the test. We also encourage you not to take any over the counter medications
during the 8-hour period.
The total duration of your participation in this research study including the 1-hour wait
time after test termination is estimated to be around 2 hours. UW Health requires that
people who have had a Tilt Table Test have a driver to take them home.
Protected health information (PHI) used in this study
Protected health information, also called PHI, is information about your physical or
mental health that includes your name or other information that can identify you, like
your date of birth or medical record number. To do this study, we will use the following
kinds of PHI:
 
Results of tests done as part of the study
 
Things you tell the researchers about your health
 
Information currently in your medical record. This information includes your
medical history, medications, results of other testing related to your fainting. We
will get this information from your health care providers such as UW Health.
How long will I be in this study?
You will be part of the study for 1 day. Your study participation is finished after you
complete and return the 4 and 8-hour questionnaires.
How is being in this study different from my regular health care?
This study is not part of your health care. It will not replace any medication that you may
be taking to control your fainting spells.
Do I have to be in the study? What if I say “yes” now and change my mind later?
No, you do not have to be in this study. Taking part in research is voluntary. This
means that you decide if you want to be in the study. If you decide now to take part,
you can choose to leave the study at any time. Let the researchers know if you choose
to leave the study. If you stop being in the research, already collected data may not be
removed from the study database. You may be asked if the investigator can collect data
from your routine medical care.
If you decide not to take part in the study, or leave the study later, your choice will not
affect any treatment relationship you have with healthcare providers at UW-Madison,
UW Health or any affiliated organizations, or any services you receive from them. No
IRB Approval Date: 5/23/2023
University of Wisconsin – Madison


HS IRB #: 2021-0081
Lead Researcher: Mohamed Hamdan, MD
Version: 3 dated 5/5/2023
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IRB Approval Date: 6/21/2021
University of Wisconsin – Madison
matter what decision you make, and even if your decision changes, there will be no
penalty to you. You will not lose medical care or any legal rights.
Your authorization for researchers to use your PHI does not have an end date.
However:
●
You can choose to take back your authorization for researchers to use your
health information. You can do this at any time before or during your
participation in the research.
●
If you take back your authorization, information that was already collected may
still be used and shared with others, but the researchers will no longer be able
to collect NEW information about you.
●
If you take back your authorization, you will not be able to take part in the
research study.
●
To take back your authorization, you will need to tell the researchers by
writing to the Lead Researcher,
Dr. Mohamed Hamdan
Cardiovascular Medicine
600 Highland Ave. MC 3248
Madison, WI 53792
Will being in this study help me in any way?
Being in this study will not help you directly. Your participation may benefit people in
the future by helping us learn more about the best way to prevent a vasovagal fainting
event.
This study is not a substitute for your regular medical care. You should continue to see
your regular medical providers.
What are the risks?
Risk Related to CPC: As with all medications, there are side effects or risks. The results
from our first study with CPC showed that the drug was safe. There may be other risks
and side effects that are not know at this time.
The common risks related to CPC include
 
Rapid heartbeat or awareness of your heartbeats called palpitations
 
Increase in blood pressure
 
Oral discomfort
 
Stomach discomfort
 
Headache
 
Trouble falling asleep or staying asleep or insomnia
 
Anxiety or excitability
IRB Approval Date: 5/23/2023
University of Wisconsin – Madison


HS IRB #: 2021-0081
Lead Researcher: Mohamed Hamdan, MD
Version: 3 dated 5/5/2023
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IRB Approval Date: 6/21/2021
University of Wisconsin – Madison
The rare risks related to taking CPC include:
 
Aspiration or fluid entering the lungs following the sips of water if you were to
faint
Risks Related to the Tilt Table Test: Tilt Table Testing is generally safe and
complications are rare. The known risks of the test include:
 
Low blood pressure
 
Pauses between heart beats
 
Nausea or vomiting after fainting
 
Weakness that can last several hours
 
Headache – if you are given nitroglycerin.
These symptoms usually improve when the table is placed flat.
There is a risk that your information could become known to someone not involved in
this study.
Reproductive Risks:
The study drug may harm a fetus or breastfeeding baby. If you are pregnant or
breastfeeding, you cannot take part in this study. If you are able to become pregnant,
you must have a negative pregnancy test on the day of study tilt testing.
Will being in this study cost me anything?
There will be no cost to you for being in the study.
Will I be paid or receive anything for being in this study?
We will pay you $200 for completing this study. Payment will be made after we have
received the surveys you completed at home.
What happens if I am injured or get sick because of this study?
If you are injured or get sick because of this study, medical care is available to you
through UW Health, your local provider, or emergency services, as it is to all sick or
injured people.
 
If it is an emergency, call 911 right away or go to the emergency room.
 
For non-emergency medical problems, contact the study team for instructions or
contact your regular health care provider.
 
Call the Lead Researcher, Dr. Hamdan at 608-263-1532 to report your sickness
or injury.
Here are some things you need to know if you get sick or are injured because of this
research:
 
If the sickness or injury requires medical care, the costs for the care will be billed
to you or your insurance, just like any other medical costs.
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Lead Researcher: Mohamed Hamdan, MD
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University of Wisconsin – Madison
 
Your health insurance company may or may not pay for this care.
 
No other compensation (such as lost wages or damages) is usuallyavailable.
 
UW-Madison and UW Health do not have a program to pay you if you get sickor
are injured because of this study.
 
By signing this consent form and taking part in this study, you are not giving up
any legal rights you may have. You keep your legal rights to seek payment for
care required because of a sickness or injury resulting from this study.
How will researchers keep my research information confidential?
We have strict rules to protect your personal information and PHI. We will limit who has
access to your name, address, phone number, and other information that can identify
you. We will store this information securely. We may publish and present what we
learn from this study, but none of this information will identify you directly without your
permission.
However, we cannot promise complete confidentiality. Federal or state laws may permit
or require us to show information to university or government officials responsible for
monitoring this study. This includes access to your medical records so that study
monitors, auditors, the Institutional Review Board and regulatory authorities can verify
study procedures and/or data. These groups will maintain your confidentiality. By
signing this consent form, you are authorizing this access to your records. We may also
have to tell appropriate authorities, such as child protective services or health care
providers, if we learn during the study that you or others are at risk of harm (for
example, due to child or elder abuse, or suicidal thoughts).
Authorizing the research team to use your PHI means that we can release it to the
people or groups listed below for the purposes described in this form. Once your health
information is released outside UW-Madison or UW Health it may not be protected by
privacy laws and might be shared with others. Also, with appropriate institutional
permissions and confidentiality protections, we might use information collected during
this study for other research or share with other researchers without additional consent
or authorization from you.
Who at UW-Madison can use my information?
 
Members of the research team
 
Study Data Monitoring Committee
 
Offices and committees responsible for the oversight of research
 
Personnel who schedule or perform medical tests or procedures, handle
accounting and billing, or do other tasks related to this study
Who outside the UW-Madison may receive my information?
 
The U.S. Food and Drug Administration (FDA)
 
US Bank for support of stipend payments
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HS IRB #: 2021-0081
Lead Researcher: Mohamed Hamdan, MD
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A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as
required by U.S. Law. This Web site will not include information that can identify you. At
most, the Web site will include a summary of the results. You can search this Web site
at any time.
Will information from this study go in my medical record?
An UW Health medical record will be created for you if you do not already have one.
Some of the information we collect for this study will go in your medical record. This
includes the results of your tilt table test. Both you and your UW Health providers will be
able to see these results. A copy of this form will be placed in your medical record.
Will I receive the results of research tests?
You will have access to the Tilt Table Test Report placed in your medical record as
required by federal law. You can access the report via UW Health MyChart or by
requesting it from the UW Health medical records department. We will briefly discuss
the results of the test with you before you leave the clinic. If you have additional
questions, about the test results or concerns about your health, contact your primary
care provider. You (or your insurance company) will be responsible for costs related to
any follow-up care.
What if I have questions?
If you have questions about this research, please contact the Lead Researcher, Dr.
Hamdan, at 608-263-1532. If you have any questions about your rights as a research
subject or have complaints about the research study or study team, call the
confidential research compliance line at 1-833-652-2506. Staff will work with you to
address concerns about research participation and assist in resolving problems.
IRB Approval Date: 5/23/2023
University of Wisconsin – Madison


HS IRB #: 2021-0081
Lead Researcher: Mohamed Hamdan, MD
Version: 3 dated 5/5/2023
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IRB Approval Date: 6/21/2021
University of Wisconsin – Madison
Agreement to Participate in Research Study
You do not have to sign this form. If you refuse to sign, however, you cannot take part in
this research study.
If you sign the line below, it means that:
●
You have read this consent and authorization form.
●
You have had a chance to ask questions about the research study, and the
researchers have answered your questions.
●
You want to be in this study.
●
You give authorization for your protected health information to be used and
shared as described in this form.
Printed Name of Research Participant
Signature of Research Participant
Date
Signature of Person Obtaining Consent and Authorization
Date
**You will receive a copy of this form**
IRB Approval Date: 5/23/2023
University of Wisconsin – Madison