A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis Cutis, A Double-Blind Randomized Placebo-Controlled Trial
Phase: PHASE4
Conditions: Calcinosis Cutis
Sponsor: University of Central Florida

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
 
NCT03639779 
 
 
Date: May 15th, 2019 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 1 of 19 
Revised: December 7, 2017 
 
PROTOCOL TITLE: 
A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial  
 
PRINCIPAL INVESTIGATOR: 
David Weinstein M.D. 
UCF College of Medicine 
UCF Health 
(352) 342-4168 
David.Weinstein@ucf.edu 
 
Co-Principal Investigator: 
Adam Foley 
UCF College of Medicine 
adamfoley7@knights.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:  
Rachel Diem-Trang Truong, B.A. 
UCF College of Medicine 
racheltr@knights.ucf.edu  
 
Sub-Investigator 
Sun Kim, B.A. 
UCF College of Medicine 
sunkim@knights.ucf.edu  
 
Sub-Investigator 
Kyle Sommerfield, B.S. 
UCF College of Medicine 
ksommerf@knights.ucf.edu 
VERSION NUMBER: 
Version 2.3 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 2 of 19 
Revised: December 7, 2017 
 
 
 
DATE: 
9/22/2018. 
 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
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Revised: December 7, 2017 
Table of Contents 
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28.0 Error! Bookmark not defined. 
29.0 17 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 4 of 19 
Revised: December 7, 2017 
1.0 
Objectives* 
1.1 The purpose of our research is to compare the effectiveness of 40mg/ml 
sodium thiosulfate (STS) solution to normal saline (0.9% sodium chloride) when 
injected intralesionally for the treatment of calcinosis cutis. Our specific aim is to 
assess the response of dystrophic and idiopathic calcinosis cutis to the injections 
of sodium thiosulfate in our patients.   
1.2 Our hypothesis is that three injections of STS, each spaced one month apart, 
will significantly improve our patients’ calcinosis cutis condition to a point where 
they are effectively clear or have a 2-point improvement in their Physician Global 
Assessment (PGA) scores when compared to normal saline.  
 
2.0 
Background* 
 
2.1 Calcium plays an important role in the growth and differentiation of the skin.1 As a 
result, dysregulation of calcium can have dermatologic consequences. One of these 
consequences results in a condition known as calcinosis cutis. This is an uncommon 
dermatologic condition in which calcium deposits are formed in the skin and result in 
cutaneous calcification. There are various types of this condition, including dystrophic, 
metastatic, iatrogenic, and idiopathic.1,2 Our research, however, will be focused on 
dystrophic and idiopathic calcinosis cutis. These forms often present in areas of the skin 
that have been previously damaged, and these patients often have no fundamental 
metabolic irregularities in calcium regulation.1 It is believed that the calcification 
develops when an associated disease causes tissue damage. This damage allows calcium 
to move into the affected area and crystallize.1 Another line of thinking is that the acidity 
which follows cell damage may have an effect on local calcium inhibitory processes.1 
Dystrophic Calcinosis cutis is commonly associated with autoimmune connective tissue 
disorders such as scleroderma, dermatomyositis, and cutaneous lupus erythematosus.1,2 
Other etiologies may include panniculitis, genetic disorders, infections, neoplasms, and 
trauma1.  
 
2.2 There are a variety of potential treatments for dystrophic calcinosis cutis which 
depends upon factors such as size, location, and etiology. These treatments include 
surgical excision, bisphosphonates, warfarin, tumor necrosis factor inhibitors, among 
others2. However, these often have varying degrees of success and none of which are 
FDA-approved.2 One studied treatment involves the drug sodium thiosulfate. Sodium 
thiosulfate (STS) has been used successfully in a number cases topically, intravenously 
(IV), and intralesionally by increasing the solubility of the cutaneous calcium deposits. 
There have been several case reports examining STS topically for several months.3–7 
Potential downsides to topical treatments are that they may not penetrate the skin deep 
enough to affect the calcifications, and patients must strictly adhere to the application 
directions. Additionally, STS has been used intravenously with success.3,8,9 However, 
there have been cases of patients discontinuing IV STS due to its side effects of fatigue 
and nausea.10 There have also been cases in which there was a lack of response to IV 
STS.9,10  

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 5 of 19 
Revised: December 7, 2017 
 
2.3 We wish to examine STS intralesionally (IL) since this would allow for minimization 
of the side effects of the IV treatment, higher local concentrations than the topical 
approach, and easier accessibility of the affected site(s). Intralesional STS has been used 
in a number of cases to treat dystrophic calcinosis cutis with great success.11–13 However, 
from the literature, there are currently no prospective studies which compare the efficacy 
of STS to normal saline which is the gap in knowledge that we are attempting to address.  
Our prospective study will allow us to address this gap in knowledge by 
comparing the intralesional administration of STS to normal saline for the treatment of 
dystrophic and idiopathic calcinosis cutis lesions. If successful, this study will contribute 
significantly to demonstrating the efficacy of IL STS for dystrophic and idiopathic 
calcinosis cutis and could be a stepping stone for development of more effective 
treatments.  
 
3.0 
Inclusion and Exclusion Criteria* 
3.1 Subjects will be screened in person at the UCF Health Clinic in Lake Nona. 
Subjects will be screened and evaluated in the clinic to verify diagnosis through 
history, physical findings, health records, and previous labs. Subjects who fit the 
diagnosis of dystrophic or idiopathic calcinosis cutis will be asked whether they 
wish to participate in the study. Subjects will not be recruited from a search of 
their medical records (see Section 22: Recruitment Methods). Female subjects 
who require a urine pregnancy test as part of their screening will be asked to give 
verbal informed consent for the test prior to the completion of screening. 
3.2 Screening Criteria 
• Inclusion Criteria:  
o Male or female adult 18 years of age or older  
o Must have health insurance will be eligible to participate 
o Must have a current diagnosis of dystrophic or idiopathic calcinosis cutis  
o Subjects must have at least 2 lesions of at least 2mm in size 
 
• Exclusion Criteria:  
o Unable to read and speak English 
o Allergy to any component of the sodium thiosulfate solution  
o Adults unable to consent 
o Individuals who are not yet adults (infants, children, teenagers) 
o Pregnant women 
o Women who are breastfeeding 
o Prisoners 
 
4.0 
Study-Wide Number of Subjects* 
 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 6 of 19 
Revised: December 7, 2017 
4.1. We plan on enrolling 12 subjects with the aim to accrue 10 subjects who successfully 
screen for eligibility for the study. This number was derived on consultation 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 the UCF Health clinic 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 three 
months. During these three months, subjects will be required to come to UCF 
Health Clinic at 9975 Tavistock Lakes Blvd., Orlando, FL 32827 for a total of 
four appointments: 
• Timeline: 
o Week 0 (Visit 1): 90 minutes 
o 48-hour post-treatment follow-up phone call: 5 minutes 
o Week 4 (Visit 2): 90 minutes 
o Week 8 (Visit 3): 90 minutes 
o Week 12 (Visit 4): 15 minutes 
• Ten months is the anticipated length of time to recruit subjects  
• The study is expected to be completed by April 2019. 
 
8.0 
Study Endpoints* 
8.1 Study endpoints: 
• Primary: 
o Change in size of study lesions 
o Change in Physician Global Assessment 
o Visual Analog Scale of pain of injection 
• Secondary: 
o Adverse Events 
 
8.2 Primary and secondary safety endpoints 
• Primary safety endpoints: Serious adverse event due to IL STS, will be 
required to withdraw.  
• Secondary safety endpoints: 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 7 of 19 
Revised: December 7, 2017 
o Intolerance to pain associated with injections, will be required to 
withdraw. 
o Vasovagal reaction. If a subject develops a vasovagal reaction, he 
or she will be given the option to withdraw but will not be required 
to withdraw. 
o If a subject experiences a mild to moderate adverse event he or she 
will be given the option to withdraw but will not be required to 
withdraw. 
 
9.0 
Procedures Involved* 
9.1 Our study is prospective double-blind randomized placebo-controlled trial that seeks 
to compare STS to a placebo saline when injected intralesionally for the treatment of 
dystrophic or idiopathic calcinosis cutis. 
 
9.2 Timeline 
• Subject visits 
o The sodium thiosulfate and saline solution will be prepared the same day 
as the subject’s baseline visit after consent to participate is obtained. 
 
o Baseline Visit 
§ Minute 00-15: 
§ Informed consent, HIPAA authorization, and screening and 
enrollment process. 
 
o Minute 15-30: 
§ Obtain demographics and medical history via Demographics Form 
and Medical History Form (attached) 
§ Selection of 2 lesions of dystrophic or idiopathic calcinosis cutis. 
• Note: The lesions must be at least 2mm in diameter and no 
larger than 2cm in diameter. If a lesion smaller than 2cm is 
not available then a 2 cm x 2 cm portion of a larger lesions 
will be used. 
§ One lesion will be “Lesion A”, and the other will be “Lesion B” 
for the entire study duration. 
§ Lesions will be labeled with their corresponding letter ‘A’ and ‘B’ 
with a marker and photographed 
§ Assessment of calcinosis cutis lesions via Case Report Form (see 
attached). 
§ Administration of STS and normal saline. 
 
o Minute 30-90: 
§ Monitoring of subject for adverse events 
• 48-hour follow-up phone call: 
o Minute 0-5: 
§ Brief phone call to assess for any adverse reactions 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 8 of 19 
Revised: December 7, 2017 
§  
 
• 1-month (+/- 8 days) Follow-up  
o Minute 00-30:  
§ Lesions will be labeled with their corresponding letter ‘A’ and ‘B’ 
with a marker and photographed 
§ Assessment of calcinosis cutis via Case Report Form (attached) 
§ Administration of STS and normal saline. 
o Minute 30-90: 
§ Monitoring of subject for adverse events 
§ Debrief of subject 
 
• 2-month (+/- 8 days) Follow-up  
o Minute 00-30:  
§ Lesions will be labeled with their corresponding letter ‘A’ and ‘B’ 
with a marker and photographed 
§ Assessment of calcinosis cutis via Case Report Form (attached) 
§ Administration of STS and normal saline 
o Minute 30-90: 
§ Monitoring of subject for adverse events 
§ Debrief of subject 
 
• 3-month (+/- 8 days) Follow-up  
o Minute 00-15:  
§ Lesions will be labeled with their corresponding letter ‘A’ and ‘B’ 
with a marker and photographed 
§ Assessment of calcinosis cutis via Case Report Form (attached) 
• During each visit subjects will be monitored for any adverse events and asked 
about any potential adverse events since the last visit. Any adverse events will be 
logged on the Adverse Events Form (see attached). 
• Visit 1 will be followed with a 48-hour post-treatment phone call to assess for any 
adverse events. 
• After all subjects have completed their participation, photographs of lesions will 
be reviewed by Dr. Sami who will fill out the Independent Observer Case Report 
Form (see attached) for each visit. He will be blinded as to which lesions received 
which treatment and at which visit in the study the lesions were photographed. 
 
• Screening and consent 
o First, each subject 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 then be filled out by the principal investigator 
with the research subject. If necessary, a pregnancy test will be performed. 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 9 of 19 
Revised: December 7, 2017 
• Solution preparation 
o 50 ml vials of sodium thiosulfate (250mg/ml) will be used for preparation 
of the treatment solution. 
§ The solution from the bottle will be diluted in a ratio of 1 part 
sodium thiosulfate 250mg/ml to 5.25 parts sterile water to yield a 
40mg/ml solution of sodium thiosulfate.14 This is done to make 
the final solution as close to isotonic as possible.  
o 30 ml vials of sodium chloride 0.9% will be used for the control 
treatment. 
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 drawn up by Dr. David Weinstein the day of use and 
discarded immediately after use. 
o Treatment and control will be randomized once for the entire study and 
all subjects based upon a one-time flip of a coin as follows: 
§ If coin flip is heads: all “A” lesions will receive STS and all “B” 
lesions will receive normal saline 
§ If coin flip is tails: all “A” lesions will receive normal saline and 
all “B” lesions will receive STS 
§ This result will be recorded on the Unblinded Treatment 
Document (See attached). 
§ Dr. Weinstein will not be notified of the result until after 
completion of the study so as to keep him blinded. 
o The syringes will be labeled with an “A” or “B” label for blinding by 
Adam Foley, or Amelia Winter. 
 
• Administration of study solutions 
o A volume of 0.1 ml/cm2 of normal saline or STS will be injected into 
each lesion. Therefore, a maximum of 0.4ml of 40mg/ml STS or 16mg of 
STS (given maximum size of 2 cm x 2 cm) will be used per visit per 
subject. 
o The same treatment lesion will be injected only with STS every injection 
and the same control lesion will be injected only with normal saline 
(0.9% sodium chloride) every injection. In other words, “Lesion A” will 
always be injected with solution A and “Lesion B” will always be 
injected with solution B. 
o Dr. Weinstein, a board-certified dermatologist, will be administering all 
injections of STS and normal saline to minimize risks for subjects. 
 
• 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 
 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 10 of 19 
Revised: December 7, 2017 
 
9.3 Risk Management: 
• Subjects will be directly observed during the administration of the STS and 
normal saline for any adverse events. An anaphylaxis kit is available in clinic 
should any subject experience such an event. The principal investigator is 
certified in basic cardiopulmonary life support and an AED is present in the 
facility. Subjects will be provided with the phone number of the PI should any 
issues related to participation in the study arise.  
 
• Sodium thiosulfate is currently FDA-approved for as an antidote in the treatment 
of cyanide poisoning. FDA phase III studies are currently being conducted for use 
in calciphylaxis. 
 
• 0.9% Sodium chloride is currently FDA-approved for parenteral replenishment of 
fluid, diluting or dissolving drugs for intravenous, intramuscular or subcutaneous 
injection, according to instructions of the manufacturer of the drug to be 
administered. 
 
• Sterile water is currently FDA-approved as a solvent or diluent vehicle for 
parenterally administered drugs or solutions and as a source of water for 
parenteral fluid replenishment after suitable additives are introduced. 
 
• The following are the source documents (see attached): 
o Subject ID Assignment Log 
o Screening and Enrollment Log 
o Drug Accountability Log 
o Unblinded Treatment Document 
o Eligibility Form 
o Demographics Form 
o Medical History Form 
o Case Report Form 
o Independent Observer Case Report Form 
o Adverse Event Form 
o Photographs of study lesions 
• Details regarding the storage of the above information is outlined in Section 11.3.  
 
9.4 Data to be collected 
• Age 
• Gender 
• Race 
• Ethnicity 
• Medical History  
o Past Medical and Surgical History 
o Medications 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 11 of 19 
Revised: December 7, 2017 
o Allergies 
o Social History 
§ Tobacco use 
§ Alcohol use 
o Laboratory Results 
• Size of lesions 
• Visual Analog Scale for Pain (VAS Pain) 
• Physician Global Assessment (PGA)  
• Photographs will also be taken of all study lesions during every assessment 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 Data will be reported descriptively [mean and standard deviation; median (min-max) 
and frequency and percentage]. Interrater reliability of PGA will be conducted using 
Cohen’s kappa statistic. As a second step, differences across times and between groups 
will be explored with non-parametric tests, such as Kruskal-Wallis test and the Mann 
Whitney U test. Statistical significance will be tested at p<.05. 
 
The data will be analyzed for significant differences with aid of a statistician. The results 
of the data analysis will be graphed for each parameter. 
 
11.2 For our study, we will recruit up to 12 adult male and female volunteers ages 18 
years and older. This number is estimated from clinical knowledge of the cases 
that present to treatment on an annual basis at the research site. Furthermore, a 
review of the existing literature suggests that the targeted sample size is 
commensurate to other published studies.3,4,13,5–12 
 
 
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, Unblinded 
Treatment Document, Demographics Forms, Medical History Forms, Eligibility 
Forms Case Report Forms, Independent Observer Case Report Forms, Adverse 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 12 of 19 
Revised: December 7, 2017 
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 research 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.) 
• 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). 
 
11.4 Data will be verified for correctness by 2 of the investigators after entry to 
REDCap. 
 
11.5 Not applicable. See above section for how data will be handled study-wide 
as this is a single center, single site study. 
 
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 adverse event 
data after 5 out of 10 subjects have completed the study. 
• If there are more severe adverse events in the treatment lesions compared to the 
control lesions with p < 0.05 then the study will be suspended immediately. 
  
13.0 Withdrawal of Subjects* 
 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 13 of 19 
Revised: December 7, 2017 
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 
Procedures for orderly termination: 
• 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 any of the study visits if the 
subject is unable or unwilling to do the follow up visits. 
 
13.3 
Procedures for subject withdrawal: 
• 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. 
• Orderly termination will proceed at the end of study period for all subjects. 
 
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 minimal pain upon injection and infiltration of STS or normal 
saline. 
• Minimal (<27%) risk of nausea and vomiting15 
• Low risk of hypotension, headache, disorientation15 
• Negligible bleeding or bruising 
• Negligible risk of infection  
 
The procedures in this research are known to hurt a pregnancy or fetus in the following 
ways:  
Sodium Thiosulfate Injection is Pregnancy Category C. There are no adequate and well-
controlled studies in pregnant women. Sodium Thiosulfate Injection should be used 
during pregnancy only if the potential benefit justifies the potential risk to the fetus. 
There are no reported epidemiological studies of congenital anomalies in infants born to 
women treated with sodium thiosulfate during pregnancy. In animal studies, there are no 
teratogenic effects in offspring of hamsters treated during pregnancy with sodium 
thiosulfate in doses similar to those given intravenously to treat cyanide poisoning in 
humans. Other studies suggest that treatment with sodium thiosulfate ameliorates the 
teratogenic effects of maternal cyanide poisoning in hamsters. In other studies, sodium 
thiosulfate was not embryotoxic or teratogenic in mice, rats, hamsters, or rabbits at 
maternal doses of up to 550, 400, 400 and 580 mg/kg/day, respectively. 
 
 
15.0 Potential Benefits to Subjects* 
15.1 Potential benefits to subjects include: 
• Possible improvement of cutaneous calcinosis lesions. 
 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 14 of 19 
Revised: December 7, 2017 
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 subjects. 
 
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 and the initial/baseline study visit will take place athe UCF 
Health clinic in Lake Nona. 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 (N=10) makes it likely that the required 
number of subjects will be recruited in less than 8 months. Drs. Weinstein 
and Sami combined see more than half this number of patients with 
calcinosis cutis annually. In addition, the rheumatologists at UCF Health 
see at least as many patients with calcinosis cutis. 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 will be conducted at the UCF Health Clinic, see section 
19. Setting. 
• While the chances of a research related injury are extremely rare, subjects 
will be required to have health insurance in order to participate in this 
study. Treatment for research related injury will be made available, 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
Page 15 of 19 
Revised: December 7, 2017 
however costs associated with this treatment will be billed to the subject's 
insurance company. Costs not covered by the subject's insurance company 
will be the subject's responsibility. 
• 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 
sodium thiosulfate has been received. Patients with a diagnosis of calcinosis cutis 
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 calcinosis cutis) 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 calcinosis 
cutis. As stated, medical records will not be searched for patients with a diagnosis 
of calcinosis cutis.  
 
22.4 
An e-mail and within clinic advertisement may be used to recruit patients 
(see attached Advertisements). This is a small pararaph 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 
paragraph describing the study will be posted on the UCF Health website (see 
attached Advertisements). 
 
22.5 
Subjects will not be compensated for their time. 
 
23.0 Local Number of Subjects 
23.1 
We plan to enroll approximately 12 subjects. 

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23.2 
We anticipate most subjects that are 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 12 subjects need to be enrolled and screened to 
obtain 10 eligible subjects.  
 
24.0 Provisions to Protect the Privacy Interests of Subjects 
24.1 
Subjects will be in the same general vicinity during the study and will be 
recruited from the UCF Health Clinic. Therefore, there will be the possibility that 
subjects 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, subjects 
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 subject’s insurance company. 
Costs not covered by subject’s insurance company will be the subject’s 
responsibility. 
 
26.0 Economic Burden to Subjects 
26.1 
Subjects have to give his or her time (approximately 5 hours) and bear any 
transportation costs (gas, tolls, etc.). If the subject’s health insurance does not 
cover the costs for the 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: 
• 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 

A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
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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 will be documented in writing on the Informed 
Consent and HIPAA Authorization. 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 subjects will be required to complete and sign the informed written consent 
document and HIPAA Authorization to ensure that there is no coercion in the study. The 
informed consent documents will be signed both by the subject and by the principal 
investigator (see attached “Informed Consent” and “HIPAA authorization”).  
 
29.0 Drugs or Devices 
29.1 
Sodium thiosulfate being used will be stored in a bag labeled “For 
Research” in a locked medication cabinet in a locked room at the UCF Health 
clinic in Lake Nona. This will only by accessible by authorized research 
personnel.  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). 
29.2 
The sodium thiosulfate and normal saline solutions are not investigational 
drugs and are readily available FDA-approved medications. 
 
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A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
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A Comparative Study of the Efficacy of Intralesional Sodium Thiosulfate Versus 
Intralesional Normal Saline for the Treatment of Dystrophic and Idiopathic Calcinosis 
Cutis, A Double-Blind Randomized Placebo-Controlled Trial 
 
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