The Effect of Abobotulinum Toxin A on the Symptoms of Raynaud's Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial
Phase: PHASE4
Conditions: Raynaud Phenomenon
Sponsor: University of Central Florida

The Effect of Abobotulinum Toxin A on the Symptoms of Raynaud’s Phenomenon, a 
Double-Blind Randomized Placebo-Controlled Trial 
 
 
NCT03639766 
 
 
Date: September 26th, 2018 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
Page 1 of 20 
Revised: December 7, 2017 
 
PROTOCOL TITLE: 
 
The Effect of Abobotulinum Toxin A on the Symptoms of Raynaud’s Phenomenon, a 
Double-Blind Randomized Placebo-Controlled Trial 
 
PRINCIPAL INVESTIGATOR: 
 
David Weinstein, M.D. 
UCF College of Medicine, UCF Health 
(407) 266 – 3627 
david.weinstein@ucf.edu 
 
Co-Principal Investigator:  
Naveed Sami M.D. 
UCF Health 
Naveed.Sami@ucf.edu 
 
Co-Principal Investigator:  
Amelia Winter, B.A. 
UCF College of Medicine 
arwinter@knights.ucf.edu 
 
Co-Principal Investigator: 
Adam Foley, B.S. 
UCF College of Medicine 
adamfoley7@knights.ucf.edu 
 
Co-Principal Investigator:  
Sun Kim, B.A. 
UCF College of Medicine 
sunkim@knights.ucf.edu  
 
Co-Principal Investigator: 
Samantha Prabakaran, B.S. 
UCF College of Medicine 
sprabakaran@knights.ucf.edu 
 
Sub-Investigator 
Rachel Diem-Trang Truong, B.A. 
UCF College of Medicine 
racheltr@knights.ucf.edu  
 
 
Sub-Investigator 
Kyle Sommerfield, B.S. 
UCF College of Medicine 
ksommerf@knights.ucf.edu 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
Page 2 of 20 
Revised: December 7, 2017 
 
 
 
VERSION NUMBER: 2 
 
 
DATE: 
9/26/2018 
 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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Revised: December 7, 2017 
 
Table of Contents 
1.0 
Objectives* .............................................................................................................. 4 
2.0 
Background* ............................................................................................................ 4 
3.0 
Inclusion and Exclusion Criteria* ............................................................................ 5 
4.0 
Study-Wide Number of Subjects* ........................................................................... 6 
5.0 
Study-Wide Recruitment Methods* ........................................................................ 6 
6.0 
Multi-Site Research* ............................................................................................... 6 
7.0 
Study Timelines* ..................................................................................................... 6 
8.0 
Study Endpoints* ..................................................................................................... 6 
9.0 
Procedures Involved* ............................................................................................... 7 
10.0 Data and Specimen Banking* ................................................................................ 12 
11.0 Data Management* and Con=dentiality ................................................................ 12 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* ........................ 14 
13.0 Withdrawal of Subjects* ........................................................................................ 14 
14.0 Risks to Subjects* .................................................................................................. 14 
15.0 Potential Bene=ts to Subjects* .............................................................................. 15 
16.0 Vulnerable Populations* ........................................................................................ 15 
17.0 Community-Based Participatory Research* .......................................................... 15 
18.0 Sharing of Results with Subjects* ......................................................................... 15 
19.0 Setting .................................................................................................................... 15 
20.0 Resources Available ............................................................................................... 15 
21.0 Prior Approvals ...................................................................................................... 16 
22.0 Recruitment Methods ............................................................................................. 16 
23.0 Local Number of Subjects ..................................................................................... 17 
24.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 17 
25.0 Compensation for Research-Related Injury ........................................................... 17 
26.0 Economic Burden to Subjects ................................................................................ 17 
27.0 Consent Process ..................................................................................................... 17 
28.0 Process to Document Consent in Writing .............................................................. 18 
29.0 Drugs or Devices .................................................................................................... 18 
 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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Revised: December 7, 2017 
 
1.0 
Objectives* 
1.1 This study aims to investigate the effect of abobotulinum toxin A on 
the symptoms of Raynaud’s phenomenon. By studying the effect of 
abobotulinum toxin A on Raynaud’s symptoms among a more 
diverse population we hope to provide insight into the patients most 
likely to benefit from abobotulinum toxin A.   
1.2 Our hypothesis is that hands that receive injections of abobotulinum 
toxin A will experience greater relief from symptoms compared to 
hands which do not 
2.0 
Background* 
2.1 Raynaud’s phenomenon affects up to 20% of the population, and is 
commonly associated with many autoimmune and inflammatory 
diseases.1 It affects over 90% of scleroderma patients, but also 
affects over 10% of patients with systemic lupus, dermatomyositis, 
rheumatoid arthritis, and primary Sjӧgren’s syndrome.2 Additionally, 
Raynaud’s phenomenon associated with an immunological disease is 
commonly has severe progression and can lead to amputation of the 
affected digits.2 Symptoms of Raynaud’s phenomenon are a result of 
worsened circulation to the extremities, particularly in the hands. A 
decrease in circulation leads to ischemia of the tissues, causing pain 
and functional limitations as well as ulcers and gangrene.3 This can 
prove extremely debilitating to patients, reducing quality of life. 
Treatment options include medications which seek to increase 
vasodilation, most commonly calcium channel blockers.4 If patients 
fail to improve under pharmacological interventions, surgery is often 
required to alleviate symptoms or remove ischemic and gangrenous 
tissue.5 However, studies have shown that botulinum toxin (BoNT) 
reduces symptoms in certain patient populations with Raynaud’s 
phenomenon.6-9  
2.2 BoNT works as a vasodilator by blocking the release of 
neurotransmitters and thereby decreasing the muscular sympathetic 
response.10 Therefore, the muscle relaxes and in the case of vascular 
muscle, allows for vasodilation of the blood vessel. Although 
approved by the FDA to treat muscle spasms, the specific use of 
BoNT for the treatment of Raynaud’s phenomenon is not 
recognized.11 Despite its off-label use, multiple studies support the 
benefits of using BoNT as a treatment for Raynaud’s phenomenon.12 
2.3 A 2014 study by Neumeister and colleagues shows BoNT improves 
blood flow in the hand as well as reduces pain and improves 
function.7 However, studies have focused on specific patient 
populations, such as that of scleroderma or systemic sclerosis.6,13 
Additionally, studies have lacked a coordinated methodology with 
some lacking double-blind experimentation, a control group, or 
appropriate treatment dosage. Our prospective double-blind 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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Revised: December 7, 2017 
 
randomized control trial seeks to compare a single formulation of 
BoNT, aboboutlinum toxin A (Dysport), to a placebo saline group, 
studying the effect of BoNT on Raynaud’s symptoms among a more 
diverse population to provide insight into the patients most likely to 
benefit from BoNT. Additionally, we hope that if we have positive 
findings that this data could be used to justify insurance coverage of 
BoNT in Raynaud’s phenomenon. With BoNT costing hundreds to 
thousands of dollars per treatment, it can prove a financial burden for 
patients relying on BoNT for relief from symptoms and prevention 
of amputation.14 Preliminary findings from this study could be used 
to justify further studies for a new indication for Raynaud’s 
phenomenon thus improving patients’ chances for coverage and ease 
of access.  
3.0 
Inclusion and Exclusion Criteria* 
3.1 For this study, patients at UCF Health will be screened in person for 
eligibility using the following inclusion criteria listed in 3.2. 
Screening will be performed by Dr. Weinstein or Dr. Sami. (See 
attached “Eligibility Screening”) 
3.2 Screening Criteria  
• Inclusion Criteria: 
o Male or female adult between 18 and 80 years of 
age 
o Must have health insurance 
o Must have a current diagnosis of Raynaud’s 
phenomenon 
• Exclusion Criteria:  
o Allergy to abobotulinum toxin A or its components 
o Diagnosis of myasthenia gravis 
o Previously received abobotulinum toxin vaccine 
o Previously undergone upper extremity vascular 
surgery (including surgical sympathectomy) 
o Currently receiving aminoglycoside antibiotics 
o Received abobotulinum toxin A treatment in either 
hand in the past 6 months 
o Pregnant women 
o Women currently breastfeeding 
o Current tobacco smoker (use in the past 12 months) 
o Unable to read and speak English 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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o Adults unable to consent 
o Individuals who are not yet adults (infants, children, 
teenagers)Prisoners 
4.0 
Study-Wide Number of Subjects* 
4.1 We plan on enrolling 20 subjects with the aim to accrue 16 subjects 
who successful screen for eligibility for the study.  This number was 
derived from a power analysis performed with Bee Nash. 
5.0 
Study-Wide Recruitment Methods* 
5.1 
Not applicable. This is not a multicenter research study and 
research will only be conducted at UCF Health clinics in Lake Nona. 
Local recruitment methods are described in section 19.0 Setting.  
6.0 
Multi-Site Research* 
6.1 
Not applicable. This is not a multi-site research project. Research 
will only be conducted at the UCF Health clinic in Lake Nona. 
7.0 
Study Timelines* 
7.1 Subjects are expected to participate in this study for a total of twelve 
months. During these twelve months, subjects will be required to 
come to UCF Health Clinic at 9975 Tavistock Lakes Blvd., Orlando, 
FL 32827 for a total of five appointments: 
• Baseline appointment: 1 hour 
• 48-hours follow-up phone call: 5 minutes 
• 1-month follow-up appointment: 15 minutes 
• 3-month follow-up appointment: 15 minutes 
• 6-month follow-up appointment: 15 minutes 
• 12-month follow-up appointment: 15 minutes 
• For the first 3 months subjects will be asked to complete a weekly 
survey either online or on paper to bring in. 
• For the final 9 months subjects will be asked to complete a 
monthly survey either online or on paper to bring in. 
• Ten months is the anticipated length of time to recruit participants. 
• The study is expected to be completed by October 2019. 
8.0 
Study Endpoints* 
8.1 Primary endpoints: Participation in the study will end 12 months 
after the baseline visit or if the patient elects to be removed from the 
study, whichever comes first. 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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Revised: December 7, 2017 
 
8.2 Primary and secondary safety endpoints: adverse reaction to the 
abobotulinum toxin A solution. If a participant develops a reaction, 
he or she will be given the option to withdraw but will not be 
required to withdraw, unless life threatening. 
9.0 
Procedures Involved* 
9.1 Our study is a double-blind randomized placebo-controlled trial.  
• Treatment arm: Injection of 300 units of abobotulinum toxin A in 
10 ml of non-bacteriostatic normal saline to chosen hand. 
• Control arm: Injection of 10 ml of non-bacteriostatic normal saline 
to chosen hand. 
• Randomization will be determined by coin flip as follows: 
o Heads: Right hand – treatment arm; Left hand – 
control arm. 
o Tails: Right hand – control arm; Left hand – 
treatment arm. 
9.2 Timeline 
• Subject visits 
o The abobotulinum toxin A solution and saline 
solution will be prepared the same day as the 
subject’s baseline visit 
o Baseline Visit 
a. Minute 00-20: 
i. Screening and consent process in 
screening room 
b. Minute 20-40:  
i. Assessment of baseline Raynaud’s 
symptoms via Baseline Case Report 
(attached) and photographs will be 
taken of both hands 
ii. Administration of abobotulinum 
toxin A solution and normal saline 
solution 
c. Minute 40-60: 
i. Review post-procedure instructions 
and how to complete Brief Follow-
up Case Reports. Observe subject for 
any adverse reaction. 
o 48-hour follow-up phone call: 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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a. Minute 0-5: 
i. Brief phone call to assess for any adverse 
reactions.  
o 1-month (+/- 8 days) Follow-up  
a. Minute 00-15:  
i. Assessment of Raynaud’s symptoms 
via Follow-up Case Report 
(attached) and photographs will be 
taken of both hands 
o 3-month (+/- 15 days) Follow-up 
a. Minute 00-15:  
i. Assessment of Raynaud’s symptoms 
via Follow-up Case Report 
(attached) 
o 6-month (+/- 15 days) Follow-up 
a. Minute 00-15:  
i. Assessment of Raynaud’s symptoms 
via Follow-up Case Report 
(attached) and photographs will be 
taken of both hands 
o 12-month (+/- 15 days) Follow-up 
a. Minute 00-15:  
i. Assessment of Raynaud’s symptoms 
via Follow-up Case Report 
(attached) and photographs will be 
taken of both hands 
• Subject surveys 
o Months 0-3: 
a. Every week the subjects will be asked to 
complete the Brief Follow-up Case Report 
either online or on a paper version given to 
the subject. 
o Months 4-12 
a. Every month the subjects will be asked to 
complete the Brief Follow-up Case Report 
either online or on a paper version given to 
the subject 
• Solution preparation 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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Revised: December 7, 2017 
 
o 300 unit vials of abobotulium toxin A will be 
reconstituted with 10 ml of non-bacteriostatic 
normal saline yielding a final concentration of 30 
units per 1 ml. 
o The solutions will be drawn up in 1 cc syringes 
utilizing a 25g needle by Dr. Weinstein. The needle 
with then be replaced with a capped 30g ½ inch 
needle.  
o All solutions will be prepared and drawn up by Dr. 
David Weinstein the day of use after consent has 
been obtained and discarded immediately after use. 
o The syringes will be labeled with a red or blue label 
for randomization by Amelia Winter, Samantha 
Prabakaran, or Dr. Naveed Sami. 
• Screening and consent: 
o Each participant will sit down with the principal 
investigator to discuss the study in depth and review 
the screening criteria. After all risks, benefits, 
alternatives, and questions have been discussed 
consent will be obtained. 
o After the informed consent form is signed, the 
eligibility screening portion of the case report form 
will be filled out by the principal investigator with 
the research subject. If necessary, a pregnancy test 
will be performed. 
• Administration of study solution: 
o 10 sites on each palm will be used (see image 
below): 
a. Two at the base of the thumb 
b. Three in the middle of the palm 
c. Five at the proximal base between each 
finger 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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Revised: December 7, 2017 
 
 
o The participants’ sites of administration will be 
cleansed with isopropyl alcohol before 
administration. Needles will be introduced at a 90-
degree angle subcutaneously. 1 ml of solution will 
be injected per site. 
o A board-certified dermatologist, Dr. Weinstein, will 
be administering all solutions to minimize risks for 
participants. 
o Subjects will be given the clinic number and asked 
to call if they think they are experiencing any 
adverse effects. 
o Subjects will be evaluated either in person or over 
the phone 1 month and 3 months after treatment. 
• Disposal protocol: 
o After use, needles will be disposed of in red harps 
container according to UCF Health policy. 
o After use, urine samples will be disposed of in the 
toilet according to UCF Health policy. 
 
9.3 
 
• Risk Management: 
o Participants will be directly observed during the 
administration of the botulinum toxin and placebo for any 
adverse events. An anaphylaxis kit is available in clinic 
should any participant experience such an event. The 
principal investigator is certified in basic cardiopulmonary 
life support and an AED is present in the facility. 
Participants will be provided with the phone number of the 

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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PI should any issues related to participation in the study 
arise.  
o Abobotulinum toxin A is the only drug used in this research 
study. It is currently FDA-approved for cervical dystonia, 
moderate to severe glabellar lines, upper limb spasticity, 
and lower limb spasticity. 
o The following are the source documents (see 
attached): 
a. Subject ID Assignment Log 
b. Screening and Enrollment Log 
c. Drug Accountability Log 
d. Eligibility Form 
e. Demographics Form 
f. Medical History Form 
g. Baseline Case Report Form 
h. Follow Up Case Report Form 
i. Brief Follow Up Case Report Form 
j. Adverse Event Form 
9.4 
Data to be collected 
• Age 
• Gender 
• Race 
• Ethnicity 
• Medical History  
o Past Medical and Surgical History 
o Medications 
o Allergies 
o Social History 
a. Tobacco use 
b. Alcohol use 
• Duration of Raynaud’s phenomenon 
• Visual Analog Scale for Pain (VAS Pain) 
• Raynaud’s Condition Score (RCS) 

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Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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• The Disabilities of the Arm, Shoulder and Hand Score 
(QuickDASH) 
• Number of digital ulcers 
• Number of attacks/episodes per week 
• Photographs of both hands will be taken during every subject visit and will 
be stored directly in the password protected HIPAA compliant network 
drive for clinical research at UCF Health. Though the photos will not 
contain any identifiers, subjects are potentially identifiable from the 
photos and thus they will be stored in the password protected HIPAA 
compliant network drive for clinical research at UCF Health. 
 
10.0 Data and Specimen Banking* 
10.1 
There will be no data or specimen banking for future use. 
 
11.0 Data Management* and Confidentiality 
11.1 The data will be analyzed for significant differences with aid of a 
statistician. A significance level of 0.05 will be used for statistical 
hypothesis testing. The results of the data analysis will be graphed 
for each parameter.  
• Categorical variables, such as sex (male and female), age, and 
comorbidities (e.g., scleroderma) will be reported descriptively, as 
frequencies and percentages. Outcomes in this study are visual 
analog scale for pain (VAS Pain), Raynaud’s Condition Score 
(RCS), and the Disabilities of the Arm, Shoulder and Hand Score 
(QuickDASH), which are continuous variables. In addition, the 
number of digital ulcers and number of attacks/episodes per week, 
which are discrete variables, will measured as outcomes. These 
continuous and discrete variables will be expressed as mean ± 
standard deviation, with standard error of the mean (SEM).   
• To assess between group differences, an Independent samples t-
tests will be conducted separately for the three time periods: 
baseline, 1-month, and 3-month. Additionally, a dependent sample 
t-test will be used to assess within-group differences from 1-month 
to 3-month, separately for the experimental and control groups. It 
is possible to use the baseline measurement as a covariate in an 
analysis of covariance (ANCOVA) and/or in a repeated measures 
ANOVA. Thus, the researchers will also explore these additional 
analyses if the sample size permits. 
• All tests will be two-sided, and p-values < 0.05 will be considered 
statistically significant. Statistical analyses will be conducted using 
SPSS 24.0 (IBM; Chicago, IL).  

PROTOCOL TITLE: The Effect of Abobotulinum Toxin A on the Symptoms of 
Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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11.2 Utilizing the statistical software G*Power it was determined that 16 
patients would be needed to detect a 2-point difference in the RCS 
among the treatment arms. (G*Power) This assumes a standard 
deviation of 1.92, power of 0.8, alpha of 0.05, and effect size (d) of 
1.04. (Merkel)  
11.3 Data will be managed as follows: 
• Data will be stored in the secure HIPAA-compliant database called 
REDCap. 
• Unique identifiers will be created using sequential numbers (i.e. 1, 
2, 4 etc.). 
• No data collection instrument in REDCap will contain identifying 
information 
• The Screening and Enrollment Log, Drug Accountability Log, Eligibility 
Forms, Demographics Forms, Medical History Forms, Baseline Case 
Report Forms, Follow Up Case Report Forms, Brief Follow Up Case 
Report Forms. Adverse Event Forms (see attached documents) will all be 
stored in the regulatory binder in a locked drawer in a locked room at UCF 
Health. Only Dr. David Weinstein will have access to this locked drawer. 
• Photographs will be taken with a UCF Health digital camera. The 
photographs will then be transferred to a folder on a password protected 
HIPAA compliant network drive for clinical reserach at UCF Health. 
After transfer of photographs to clinical research folder they will be 
deleted from the camera. Photographs will be labeled with subject ID 
number and visits number (i.e Subject 01 3-month) 
• A subject ID assignment list (see attached document “Subject ID 
Assignment List”) that links the subject name and contact 
information with their unique identifier will be stored in a separate 
folder in locked drawer in a locked room at UCF Health. Only Dr. 
David Weinstein will have access to this locked drawer. 
• Identifying information such as the “Subject ID Assignment List” 
will only be accessed by the PI and co-PIs for initial entry. It is 
possible the identifiable information may be referenced if 
questionable data are detected during data analysis (e.g.: number 
out of range, missing data). 
• The “Screening and Enrollment Log” and the “Subject ID 
assignment List” will both be disposed of in a HIPAA-compliant 
shred bin at the completion of the study. 
• Informed consents and HIPAA authorizations will be stored in 
locked drawer in a locked room at UCF Health and kept for a 
minimum of six years after the conclusion of the study (per UCF 
data retention policies.) 

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Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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• Only de-identified data will be used and exported for analysis.  
• De-identified data and photographs will be stored for a minimum 
of five years after the conclusion of the study (per UCF data 
retention policies). 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
12.1 
The plan to periodically evaluate the data collected regarding both harms 
and benefits to determine whether subjects remain safe is as follows: 
• The principal investigator and statistician will review cumulative VAS 
Pain scores, RCS data, QuickDASH, number of digital ulcers, and number 
of attacks/episodes per week data at the halfway point (8 subjects). 
• If any of the change in VAS Pain scores, RCS, QuickDASH, number of 
digital ulcers, or number of attacks/episodes per week for the treatment 
should become statistically significantly worse than the control with a p < 
0.05 then the study will be suspended immediately.  
• Alternatively, if the change in VAS Pain scores, RCS, QuickDASH, 
number of digital ulcers and number of attacks/episodes per week for the 
treatment should become statistically significantly better than the control 
with a p < 0.05 then the study will also be suspended immediately. 
13.0 Withdrawal of Subjects* 
13.1 Subjects will be withdrawn from the research without their consent if 
they become intolerant to the treatment and/or the researchers 
determine that they are too nervous, anxious to continue.  
13.2 Orderly termination will proceed at the end of study period for all 
subjects. This will simply mean no further visits and no further data 
collection will occur.  
13.3 Subjects may voluntarily terminate their participation in the research 
at any time by informing a member of the research team. A subject 
may partially withdraw from the study after the initial treatment and 
control have been administered or even during administration if the 
participant is unable or unwilling to continue or do the follow up 
visits. 
If a subject withdraws or is withdrawn from the study prior to 
completion, further data collection will be stopped. However, partial 
data already collected will be used for analysis. 
14.0 Risks to Subjects* 
14.1 There is no major anticipated risk associated with the study. 
However potential risks to the subject include: 
• Discomfort and pain upon injection and infiltration of 
abobotulinum toxin A or normal saline 
• Temporary muscle weakness that may last 6 weeks 
• Negligible bleeding or bruising 

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Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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• Minimal risk of infection (<1%)16 
• Allergy to abobotulinum toxin A solution (<1%) 
• Furthermore, true allergy to abobotulinum toxin A is extremely 
rare.17 
15.0 Potential Benefits to Subjects* 
15.1 Potential benefits are not guaranteed to subjects but include: 
• Relief from Raynaud’s phenomenon symptoms 
• Free treatment for their Raynaud’s phenomenon 
16.0 Vulnerable Populations* 
16.1 This study does not involve individual who are vulnerable to 
coercion or undue influence. 
17.0 Community-Based Participatory Research* 
17.1 This is not community-based participatory research. 
18.0 Sharing of Results with Subjects* 
18.1 There are no plans to share results with participants. 
19.0 Setting 
19.1 Research will be conducted at UCF Health:  
• Potential subjects will be identified and recruited at both the UCF Health 
clinic in Lake Nona and the UCF Health clinic on Quadrangle Blvd. 
• Screening, enrollment, initial/baseline study, and follow up study visits 
will take place at the UCF Health clinic in Lake Nona.  
• There will not be a community advisory board. 
20.0 Resources Available 
20.1 
Dr. Weinstein has significant prior experience conducting research, 
knowledge of the regulations and customs at UCF Health, and works regularly 
with patients performing dermatologic surgery. All injections will be administered 
by Dr. Weinstein. Dr. Sami has extensive experience conducting clinical research. 
In addition, the medical students involved in the project will be able to help 
significantly. Through the FIRE project Bee Nash will be able to assist with data 
analysis. 
 
20.2 
Resources available to conduct research: 
 
• The study's small sample size of 20 subjects to be enrolled in order to have 
16 subjects complete the study makes it likely that the required number of 
participants will be recruited in less than 8 months. Drs. Weinstein and 
Sami see at least this number of patients with Raynaud’s phenomenon 
annually. In addition, the rheumatologists at UCF Health see at 3 to 4 

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Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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times as many patients with Raynaud’s phenomenon. Finally, recruiting 
through the local dermatology society and advertising should supplement 
the numbers needed to complete the study. 
• Research will be conducted during Dr. Weinstein's administrative time or 
on the weekend.  
• The study will be conducted at the UCF Health Clinic, see section 19. 
Setting. 
• While the chances of a research related injury are extremely rare, 
participants will be required to have health insurance in order to 
participate in this study. Treatment for research related injury will be made 
available, however costs associated with this treatment will be billed to the 
participant's insurance company. Costs not covered by participant's 
insurance company will be the subject's responsibility. (see Consent Form 
attached) 
• All individuals assisting in the research study will be provided a copy of 
the IRB-approved protocol and given the opportunity to meet with the 
principal investigator before recruitment begins. The principal 
investigator, Dr. Weinstein, will be responsible for informing all research 
staff of their research-related duties during a personal meeting or via 
phone or email. The contact information of the principal investigator and 
co-principal investigator will be distributed to all research staff and the 
subjects. 
 
21.0 Prior Approvals 
21.1 Approval from the medical director and the HIPAA privacy officer 
of UCF Health will be obtained prior to commencing research. 
22.0 Recruitment Methods 
22.1 
The research team will start recruitment shortly after IRB approval 
and the abobotulinum toxin A has been received. Patients with a diagnosis 
of Raynaud’s phenomenon will be recruited from the UCF Health Clinic 
during a patient’s visit (medical records will not be searched for patients 
with a diagnosis of Raynaud’s phenomenon) and through advertising on 
the UCF Health website and within the UCF Health clinic.  
22.2 
The primary source of subjects will be patients at the UCF Health 
Clinic and people in the greater Orlando area. This represents a large pool 
of potential subjects from which to recruit. 
22.3 
Dr. Weinstein and Dr. Sami will rely on prior labs, pathology 
reports, and physical examination to determine if the participant has a 
diagnosis of Raynaud’s phenomenon. 
22.4 
An e-mail and within clinic advertisement may be used to recruit patients 
(see attached Advertisements). This is a small paragraph describing the study. 
This text may be displayed in the UCF Health clinic, to other providers at UCF 
Health or members of the local dermatology society. In addition, a similar small 

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Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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paragraph describing the study will be posted on the UCF Health website (see 
attached Advertisements). 
22.5 
Participants will not be compensated for their time. 
23.0 Local Number of Subjects 
23.1 We plan to enroll approximately 20 subjects. 
23.2 We anticipate most subjects that enrolled to be successfully 
screened. There may be a few subjects that will fail screening due to 
failing urine pregnancy testing. Given this, it may be that 18 to 20 
subjects need to be enrolled and screened to obtain 16 eligible 
subjects.  
24.0 Provisions to Protect the Privacy Interests of Subjects 
24.1 Subjects will be in the same general vicinity during study and will be 
recruited from UCF Health Clinic. Therefore, there will be the 
possibility that participants may know and recognize each other.  
24.2 Prior to enrollment subjects will be made aware of this possibility 
and if unacceptable, will be given the option to decline to participate. 
24.3 All investigators will have access to all of the information collected 
on the subjects. The “Subject ID Assignment Log” will be kept in a 
separate folder so that investigators will only have access to 
identifiable information if needed for data entry or if there is a data 
discrepancy. Only de-identified data will be exported and used for 
data analysis. 
25.0 Compensation for Research-Related Injury 
25.1 While the chances of a research related injury are extremely rare, 
participants will be required to have health insurance in order to 
participate in this study. Treatment for research related injury will be 
made available, however costs associated with this treatment will be 
billed to the participant’s insurance company. Costs not covered by 
participant’s insurance company will be the participant’s 
responsibility. 
26.0 Economic Burden to Subjects 
26.1 Subjects have to give his or her time (approximately 2.5 hours) and 
bear any transportation costs (gas, tolls, etc.). If the subject’s health 
insurance does not cover the costs for treatment related injury, the 
subjects will be billed for the treatment. There are no other expected 
costs that subjects will incur as a result of participating in the study.  
 
27.0 Consent Process 
27.1 Consent process: 

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Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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• The consent process will take place in person at the UCF Health 
clinic in Lake Nona. 
• Subjects will be given the option of picking up the consent and 
HIPAA authorization prior to participation to discuss with their 
primary care physician, significant other, etc., to help minimize the 
possibility of coercion or undue influence. Subjects will be able to 
wait however long they desire after obtaining the study 
information and before signing the consent and HIPAA 
authorization.  However, if the study is completed before the 
subject chooses to sign the consent then they will not be allowed to 
participate. 
• Subjects may voluntarily terminate their participation in the 
research at any time by informing a member of the research team. 
Other than the initial informed consent no other formal process 
will be done to document ongoing consent. 
• The UCF “SOP: Informed Consent Process for Research (HRP-
090)” will be followed. 
• The consent process and HIPAA authorization will be documented 
in writing. The investigator will describe the details of the study 
and answer any questions the subject may have about the study. 
Subjects will be given an informed consent and HIPAA 
authorization for the study and the primary investigator’s contact 
information. Those subjects who express interest in the study will 
be required to sign the Informed Consent form and HIPAA 
authorization to ensure that there is no coercion in the study.  
28.0 Process to Document Consent in Writing 
28.1 The UCF “SOP: Written Documentation of Consent (HRP-091)” 
will be followed. 
28.2 All participants will be required to complete and sign the informed 
written consent document (see attached) to ensure that there is no 
coercion in the study. The informed consent documents will be 
signed both by the participant and by the principal investigator (see 
attached “Informed Consent”).  
 
29.0 Drugs or Devices 
29.1 Abobotulinum toxin A being used will be stored in bag label “For 
Research” in a locked medication refrigerator in a locked room at the 
UCF Health clinic in Lake Nona. This will only be accessible by 
authorized study personal.  The medication will only be used on 
research subjects by authorized study personnel. Logging of the drug 
inventory and administration will be kept on the Drug Accountability 
Log (see attached). 

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Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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29.2 The abobotulinum toxin A and normal saline solutions are not 
investigational drugs and are readily available FDA-approved 
medications. 
 
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Devulder J, van Suijlekom H, van Dongen R, et al. 25. Ischemic pain in the 
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Raynaud’s Phenomenon, a Double-Blind Randomized Placebo-Controlled Trial 
 
 
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