Clinical trial NCT04359823
Conditions: Actinic Porokeratosis
Sponsor: Medical University of South Carolina
Start date: 2020-08-24; Completion date: 2021-04-23
Enrollment: 31 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will analyze the effects of topical lovastatin/cholesterol vs topical lovastatin alone in patients with disseminated superficial actinic porokeratosis. Patients will be divided into two groups, topical lovastatin/cholesterol and topical lovastatin alone. Patients will apply topical treatment twice daily to lesions over the course of 12 weeks. Follow up will occur in the virtual setting and photographs will be used to document progress.

Detailed description:
The purpose of this study is to evaluate the effectiveness of cholesterol/lovastatin versus lovastatin alone to treat porokeratosis. Our working hypothesis is that both topical cholesterol/lovastatin and lovastatin alone are helpful in treating patients with disseminated superficial actinic porokeratosis (DSAP). Potential subjects will be approached by their care team member to be made aware of the study at MUSC Dermatology clinics. Subsequently, members of the study team will approach their own patients to ask for participation in this study. Pertinent project information, risks, and time commitment will be relayed to subjects. If subjects show interest in participating, they will be given consent forms to either sign or bring home for consideration. If the patient is eligible for the study, he or she will be randomly assigned to one of two groups. They will have a 50/50 chance of being in either group. You will not make the choice to which group you are assigned. The two groups are Group A (cholesterol/lovastatin) and Group B (lovastatin only). The patient will not be informed of which group they are in and will not be informed of what their study medication is, allowing single-blinding. Researchers will not be masked. Initial enrollment will occur virtually. Enrolled subjects will be followed up at monthly intervals for three months via virtual check-in. At each visit, participants will undergo brief physical examination; additionally, clinical photographs of the lesion will be obtained. Photographs will be stored in the electronic medical record and stored in a departmental secure drive for further analysis of lesion features. At each visit the novel DSAP- General Assessment Scale and RAND36 QoL scale will be administered. Patients will be contacted via virtual check-in visits at weeks 4, 8, and 12. Patients will be asked about compliance and any adverse effects experienced. Participants will also be contacted by phone by study team member to assess for any adverse effects at weeks 2 and 6 of treatment. Compounded topical medication prescribed to subjects will be self-applied twice daily. These medications will be prepared by Tide Water Pharmacy Charleston, SC and Chemistry RX Philadelphia, PA. Chemistry Rx will ship the medications to the patients. They will be prepared so the study will remain single-blinded. The associated costs will not be covered by the research budget. Dermoscopic and clinical photographs will be subsequently analyzed for the presence of cornoid lamella. The team will record any additional dermoscopic or clinicals feature that may arise during the analyses. Frequency of dermoscopic and clinical features will be analyzed against clinical involution to find possible predictors.

Arms: arm 1: This arm will utilize 2% cholesterol and 2% lovastatin ointment. It will be compounded by a pharmacist. Ointment will be applied on lesional skin with occlusion twice daily for 12 weeks. arm 2: This arm will utilize 2% lovastatin ointment. It will be compounded by a pharmacist. Ointment will be applied on lesional skin with occlusion twice daily for 12 weeks.
Interventions: intervention 1: Lovastatin 2%, 2% Cholesterol Cream intervention 2: Lovastatin 2% Cream
Intervention descriptions: intervention 1: Patients selected to the study will be randomly assigned to this arm. They will have a 50% chance of being placed in this arm compared to the other arm. intervention 2: Patients selected to the study will be randomly assigned to this arm. They will have a 50% chance of being placed in this arm compared to the other arm.

Protocol documents:
ICF_002.pdf: 
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IRB Number: «ID» 
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Medical University of South Carolina 
CONSENT TO BE A RESEARCH SUBJECT 
TITLE OF RESEARCH: Topical treatment for superficial disseminated actinic porokeratosis: 
A Single-blinded Comparison Between Lovastatin/Cholesterol and Lovastatin 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
You are being asked to volunteer for a research study. Research studies are voluntary and include 
only people who choose to take part. The purpose of this research is to treat disseminated 
superficial actinic porokeratosis (DSAP) with cholesterol/lovastatin or lovastatin alone. The goal 
of treatment is to decrease DSAP lesions after 12 weeks of treatment. Moreover, we will compare 
which treatment is best. 
If you agree to participate in this study, you will be asked to apply twice daily the topical 2% 
cholesterol/2% lovastatin ointment or 2% lovastatin alone. The study is single-blinded and 
randomized, meaning you will not be told of which treatment you receive, and the decision of 
which treatment you will receive will be completely random. You have a 50% chance of receiving 
either treatment.  
Enrollment in the study will occur in one of two ways: 1. You will be enrolled after an in-person 
standard of care visit, during which the study team members will enroll you in-person. 2. You will 
be enrolled via a virtual visit by study team members.  
All subjects will be required pay for the cost of the 3-month supply of medication. For residents 
of South Carolina, the cost of the medication is approximately $85. For residents of states other 
than South Carolina, the cost is approximately $110. If you are a woman of child-bearing age, you 
will also be required to purchase a home pregnancy test which may cost up to $15. Costs involved 
with study participation are described in more detail in the cost section of the consent. 
If you are able to be enrolled in the study in-person, you will also agree to close up photographs 
and clinical photographs taken of your DSAP at the initial visit. If you enroll virtually, you must 
provide close up photographs to the study team via email. At weeks 4, 8, and 12, all subjects will 
complete a virtual check-in visit. You will take a picture (using phone camera/digital camera) of 
your lesions/skin markings with a measuring instrument. This will allow us to document the size 
of the lesions. Physical exam, photographs, and a review of your medical records will occur in the 
study. Each visit will take approximately 15 minutes. Total study length will be 12 weeks. 
Changes in size, appearance, and pain will be monitored throughout the study. 
You may directly benefit from this study as we expect DSAP will decrease in size after treatment. 
There are risks to participation that are described in this document, such as minor allergic 
irritation and local irritation. In the rare chance of significant medication absorption through your 
skin into your blood, signs and symptoms of muscle damage may occur including muscle 
soreness, twitches, and cramping. In extremely rare cases, weakness and elevated muscle proteins 
may occur. There is a possible increased risk of allergic reaction in the combination treatment 
group since there are two ingredients instead of one that you might develop an allergy to. There is 
a risk of loss of confidentiality, but every effort will be made to protect your privacy and health 
information. There is a risk of emotional discomfort with taking the questionnaires provided in 
the study. 
If you choose not to participate in the study, your decision will not affect your medical care. Your 
alternative is to not participate and receive the standard of care treatment of conservative 
management, such as local cryotherapy (freezing the lesions), 5-FU cream, and surgery. 


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A.  PURPOSE OF THE RESEARCH 
You are being asked to join this research study because you have disseminated superficial actinic 
porokeratosis (DSAP). We believe using topical cholesterol/lovastatin and lovastatin alone are 
helpful to treat patients with DSAP. 
 
We are asking for your participation to determine if there is a difference between the two treatments 
in how well they work or how safe they are. Currently, cholesterol and lovastatin are not approved by 
the Food and Drug Administration (FDA) to be used for porokeratosis. These drugs are considered to 
be investigational for the purposes for the study.  
 
Please read this consent form carefully and take your time making your decision. As your study 
doctor or study staff discusses this consent form with you, please ask him/her to explain any words or 
information that you do not clearly understand. You are being asked to participate in this study 
because you have DSAP. The study is sponsored by the MUSC Department of Dermatology and 
Dermatological Surgery. The investigator in charge of this study at MUSC is Dr. Dirk Elston. The 
study is being done at MUSC only. Approximately 50 people will take part in this study. 
 
B.  PROCEDURES 
If you agree to be in this study, the following will happen: 
 
1. 
You must have a confirmed diagnosis of DSAP by a licensed medical professional. 
2. 
You must thoroughly read and sign the informed consent after asking any necessary question 
to clarify any lack of understanding. If you enroll virtually, signature of the informed 
consent form must be completed during the initial virtual visit, prior to beginning the study 
procedures. Virtual enrollment will occur via a secure platform approved by MUSC, called 
REDCap. We will send you the REDCap link the day of your enrollment visit. 
3. 
Once enrolled in the study, you will be added to a patient list and this list will be shared 
amongst study team members alone. Patient visits and collected data will be recorded in 
documents stored in drives in computers created specifically for this research study. This 
information will be shared between study investigators and coordinators for the purpose of 
collecting and analyzing data. They are secured through MUSC’s network and will only be 
accessible by named study personnel. 
4. 
You will have a physical exam and medical history taken. You will be asked about current 
pregnancy or plans to become pregnant, as you cannot be pregnant to participate in this 
study. Subjects with child-bearing potential not currently on approved contraception will 
complete a urine pregnancy test to rule out pregnancy before being approved for the study. If 
you prefer to use a home pregnancy test, you must submit to the investigators a picture of the 
test with the date, name, the date the test was performed, and a signature to complement the 
integrity of the tests results. Only pregnancy tests with an explicitly negative result will be 
considered as acceptable.  
5. 
 Subjects with child-bearing potential will need to prevent pregnancy with an oral 


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contraceptive, intrauterine device (IUD), or implanted contraceptive. Any other type of 
pregnancy prevention is unacceptable for this study.  
6. 
If you are shown to be eligible for the study, you will be randomly assigned to one of two 
groups. This means you have a 50/50 chance (like flipping a coin) of being in either group. 
Neither the researchers nor you will make the choice to which group you are assigned. The 
two groups are Group A (cholesterol/lovastatin) and Group B (lovastatin only). This study 
will be single blinded, meaning you will not be aware which group you are in but the 
investigators will.  
7. 
Individual prescriptions will be called in and ordered at either Tidewater Pharmacy or 
Chemistry Rx by a study team member. Your assigned pharmacy will call you directly to 
coordinate medication payment and medication delivery to your address. 
8. 
Group A will apply cholesterol/lovastatin 2 times a day for a total of 12 weeks.  Group B 
will receive lovastatin alone, according to the same schedule. 
9. 
Study visit timeline: you are expected to attend virtual visits for follow-up and photographs 
at week 4, week 8, week 12 (12 weeks). Visits will be approximately 15 minutes. A typical 
virtual-visit will have you attend the visit using your computer or cell phone and discussing 
your treatment with a doctor or his/her research team who you will see on your screen and 
will be talking to you. 
10. Baseline and follow up clinical photographs will be taken of your DSAP. If the area imaged 
is close to your face, your eyes will be covered to protect your identity. If you do not want    
your eyes to be covered, you will be asked to sign a separate photograph release form. You 
will be asked to take photographs of your lesions and share them on MyChart or email. The 
anticipated measurement time is 5 minutes. If you are sharing photos via email, they must be 
deidentified photos of your legs or arms. 
11. If you are actively taking approved forms of long-term contraception (oral contraceptives, 
implantable intrauterine devices, or other hormone eluting implants), you will be allowed to 
participate as long as they have no plan to become pregnant during the course of the study. If 
this applies to you, a negative urine pregnancy test result is required for enrollment. If you 
prefer to use a home pregnancy test, you must submit to the investigators a picture of the test 
with the date, name, the date the test was performed, and a signature to complement the 
integrity of the tests results. Only pregnancy tests with an explicitly negative result will be 
considered as acceptable.  
12. Three Patient Quality of Life and disease questionnaires will be used at each visit (initial, 
weeks 4, 8, and 12) to ask you how you are currently doing with your treatment and if there 
are any changes with your quality of life due to this treatment.  
13. If you wish to discontinue treatment, notify Alan Snyder at snydeala@musc.edu or Dr. Dirk 
Elston at elstond@musc.edu as soon as possible. 
 
 
Event 
Screening 
Baseline 
 
Week4 
Week 8 
Week 12 


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Informed consent 
X 
 
 
 
Eligibility Assessment 
X 
 
 
 
Demographics 
X 
 
 
 
Physical Examination 
X 
 
 
 
Clinical photograph 
X 
X 
X 
X 
Dermoscopic 
photograph (close up 
photograph) 
X 
 
 
 
Safety 
X 
X 
X 
X 
Questionnaires 
X 
X 
X 
X 
 
C.  DURATION 
Participation in the study will take 4 visits over a period of 12 weeks. 
 
D.  RISKS AND DISCOMFORTS 
The experimental treatments may have unknown side effects. The researchers will let you know if 
they learn anything during the course of the study that might make you change your mind about 
participating in the study. 
 
The treatment you receive may prove to be less effective or to have more side effects than the other 
study treatment(s) or other available treatments. 
 
These topical ointments result in minimal systemic absorption. In the rare chance of significant 
medication absorption through the skin into your blood, muscle damage may result, causing muscle 
soreness, fasciculations, cramping, and in extremely rare cases, muscle breakdown and weakness. 
Elevated muscle proteins due to muscle breakdown may also occur. However, the vast majority of 
cases are resolved with proper hydration and simple discontinuation of the medication. Possible 
cutaneous adverse events are local irritation or allergic reaction to the components of the ointment. 
There is a risk of a loss of confidentiality of your personal information as a result of participation in 
this study that will be mitigated at all costs by the study team members. 


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Since this study is randomized, the treatment you receive may prove to be less effective or to have 
more side effects than the other study treatment(s) or other available treatments. The 
lovastatin/cholesterol combined group has increased risk of an allergic reaction compared to the 
lovastatin group due to the fact that there is two compounds in the ointment as opposed to one (the 
allergic risk of the individuals compounds are equal). Otherwise, it is believed that both groups are 
comparable risk.  
 
We do not know if the study drugs will affect embryos or an unborn fetus. Therefore, pregnant 
women are not allowed to take part in the study. If you are pregnant or become pregnant, there may 
be risks to the embryo or fetus that are unknown at this time. Women who can become pregnant must 
take a pregnancy test before the start of the study. 
 
Unless you cannot have children because of surgery or other medical reasons, you must be using an 
effective form of birth control before you start the study. You must also agree to continue to use an 
effective form of birth control for 3 month/s after taking the study drug. 
 
 
E.  MEDICAL RECORDS AND/OR CERTIFICATE OF CONFIDENTIALITY 
Information about your study participation will not be in your medical record.  This means that 
neither your research participation nor any of your research results will be included in any MUSC 
medical record. 
 
All medical history, study related information, and collected data will be stored securely in a study-
specific medical record. This will be stored in a secured drive accessible to study team members. 
Clinical and close up photographs will be included in your study-related medical record. All 
information within your medical record can be viewed by study team individuals authorized to access 
the record. We will make every effort to keep confidential all research information in the medical 
record that identify you to the extend allowed by the law. 
 
F.  BENEFITS 
The possible benefit to you is that the treatment you receive may be more effective than the other 
study treatment or than other available treatments for your DSAP, although this cannot be 
guaranteed. All benefits are not guaranteed. 
 
 
G.  COSTS 
The 3-month supply of the study drug will cost approximately $85 or $110, depending on which state 
you live in. If you live in South Carolina (SC) or near Charleston, SC, the cost of your medication 
will be approximately $85 and you can pick up your prescription in-person or have it sent to your 
residence by Tidewater Pharmacy (421 Johnnie Dodds Blvd, Mt. Pleasant, SC 29464; (843) 375-


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6310). Tidewater Pharmacy is only capable of performing in-person medication pick-up or 
medication delivery within South Carolina. 
 
If you are unable to be dispensed the medication from Tidewater Pharmacy or do not currently live in 
the state of South Carolina, your medication will cost approximately $110 and you can have the 
medication sent to your residence by Chemistry Rx Pharmacy (829 Spruce St #100, Philadelphia, PA 
19107; (855) 861-0862). The difference in costs between pharmacies is due to differences in shipping 
costs and pharmacy fees.  
 
All subjects are responsible for the cost of the drug.  
 
If you are a woman of childbearing age, you will also be required to purchase a home pregnancy test, 
which may cost up to $15 at your local pharmacy. All costs associated with physician time will be 
waived by the physician. No costs will be incurred or associated with any of the virtual visits for both 
enrollment groups (in-person or virtually.) All routine clinical care that you have undergone without 
participation in this study will be billed to you/your insurance company, such as your medication or a 
pregnancy test. All study-related tests and procedures will be not paid for by the Sponsor.  
 
If a subject is injured during the study, they will be responsible for the associated charges. Payments 
for the medication must be paid in full to Tidewater Pharmacy for the drug without a payment 
schedule. Patients are responsible for the costs of the pregnancy test as well. If the study subject 
withdraws from the research study or is removed from the study by the investigators, there will be no 
refund of any cost provided by the study team.  
 
Some insurance plans will not pay for these services for people taking part in research studies and it 
is unlikely your insurance company will cover the cost of the drug or pregnancy test. Your 
involvement in this study will not affect your health insurance coverage. You will be responsible for 
any charges that your insurance does not cover including co-payments and deductibles.  
H.  PAYMENT TO PARTICIPANTS 
 
You will not be paid for participating in this study. 
 
I.  ALTERNATIVES 
If you choose not to participate in this study, you could receive other treatments for you condition. 
The standard therapies for your condition include cryotherapy (freezing lesions using cold 
substance), surgery, light therapy, lasers (burning skin to promote new skin formation), and 5-
fluorouracil. 
 
J.  DATA SHARING 
Information about you (including your identifiable private information, photographs, and/or any 
identifiable biospecimens) may have all of your identifiers removed and used for future research 


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studies or distributed to other researchers for future research without additional informed consent 
from you or your legally authorized representative. 
K.  DISCLOSURE OF RESULTS 
Results from the study will be shared with you if you would like. 
L.  AUTHORIZATION TO USE AND DISCLOSE (RELEASE) MEDICAL INFOMRATION 
As part of this research study, your study doctor and his/her research team will keep records of your 
participation in this study. 
 
The health information MUSC may use or disclose (release) for this research study includes 
information in your medical record, results of physical exams, medical history, lab tests or certain 
health information indicating or relating to your condition.  
 
Your study doctor and his/her research team will use and disclose (release) your health information 
to conduct this study. The health information listed above may be used by and/or disclosed (released) 
to the following, as applicable: 
 
• 
The sponsor of the study including its agents such as data repositories or contract 
research organizations monitoring the study; 
• 
Other institutions and investigators participating in the study; 
• 
Data Safety Monitoring Boards; 
• 
Accrediting agencies; 
• 
Clinical staff not involved in the study whom may become involved if it is relevant; 
• 
Parents of minor children if less than 16 years old.  Parents of children 16 years old or 
older require authorization from the child; or 
• 
Health insurer or payer in order to secure payment for covered treatment; 
• 
Federal and state agencies and MUSC committees having authority over the study such 
as: 
 
o The Institutional Review Board (IRB) overseeing this study;  Committees 
with quality improvement responsibilities;  Office of Human Research 
Protections; Food and Drug Administration;  National Institutes of Health or 
Other governmental offices, such as a public health agency or as required by 
law. 
 
Those persons who receive your health information may not be required by Federal privacy laws 
(such as the Privacy Rule) to protect it and may share your information with others without your 
permission, if permitted by laws governing them.   You do not have to sign this consent form.  If you 
choose not to sign, it will not affect your treatment, payment or enrollment in any health plan or 
affect your eligibility for benefits.  However, you will not be allowed to be a participant in this 
research study. 
 
You will be given a copy of this consent form.  Your authorization will expire at the conclusion of 
this study or, if you are participating in a study designed for the development of a drug or device, 
your authorization will remain in effect until the drug or device is approved by the FDA or until the 


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company’s application to study the drug/device is withdrawn.   You have the right to withdraw your 
agreement at any time.  You can do this by giving written notice to your study doctor.  If you 
withdraw your agreement, you will not be allowed to continue participation in this research study.  
However, the information that has already been collected will still be used and released as described 
above.  You have the right to review your health information that is created during your participation 
in this study.  After the study is completed, you may request this information. 
 
Your health information will be used or disclosed when required by law.  Your health information 
may be shared with a public health authority that is authorized by law to collect or receive such 
information for the purpose of preventing or controlling disease, injury or disability and for 
conducting public health surveillance, investigations or interventions.  No publication or public 
presentation about the research study will reveal your identity without another signed authorization 
from you.   
 
If you have questions or concerns about this Authorization or your privacy rights, please contact 
MUSC’s Privacy Officer at (843) 792-8740.   
 
Regulations require that you be given a copy of the MUSC Notice of Privacy Practices (NPP) 
describing the practices of MUSC regarding your health information. One can be found at the end of 
this form. 
M.  SIGNIFICANT NEW FINDINGS 
Significant new findings that may relate to the subject's willingness to continue participation, such as 
new risk information, will be provided to the subject. Significant new findings may include an 
unexpected adverse event or an adverse event occurring at greater frequency or severity than 
previously stated in the consent process. 
N. FUTURE CONTACT 
The researcher in charge of this study might like to contact you in the future about other research 
opportunities.  
 
Please initial by your choice below for paper consents, or scroll down to the bottom of the 
screen and select your choice electronically: 
____Yes, I agree to be contacted 
____No, I do not agree to be contacted 
O. CLINICAL TRIALS.GOV  
 
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. 
 
Results of this research will be used for the purposes described in this study. This information may 


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be published, but you will not be identified. Information that is obtained concerning this research that 
can be identified with you will remain confidential to the extent possible within State and Federal 
law. The sponsor and the Food and Drug Administration (FDA) will receive copies of the research 
records. The investigators associated with this study, employees of the sponsor, the FDA, and the 
MUSC Institutional Review Board for Human Research will have access to identifying information. 
All records in South Carolina are subject to subpoena by a court of law. 
 
In the event of a study related injury, you should immediately go to the emergency room of the 
Medical University Hospital, or in case of an emergency go to the nearest hospital, and tell the 
physician on call that you are in a research study. They will call your study doctor who will make 
arrangements for your treatment. If the study sponsor does not pay for your treatment, the Medical 
University Hospital and the physicians who render treatment to you will bill your insurance 
company. If your insurance company denies coverage or insurance is not available, you will be 
responsible for payment for all services rendered to you. 
 
Your participation in this study is voluntary. You may refuse to take part in or stop taking part in this 
study at any time. You should call the investigator in charge of this study if you decide to do this. 
The data collected on you to this point remains part of the study database and may not be removed. 
Your decision not to take part in the study will not affect your current or future medical care or any 
benefits to which you are entitled. 
 
The investigators and/or the sponsor may stop your participation in this study at any time if they 
decide it is in your best interest. They may also do this if you do not follow the investigator’s 
instructions. 
 
Volunteers Statement 
 
I have been given a chance to ask questions about this research study. These questions have been 
answered to my satisfaction. If I have any more questions about my participation in this study or 
study related injury, I may contact Dr. Dirk Elston at elston@musc.edu or Alan Snyder at 910-
619-5832. I may contact the Medical University of SC Patient and Family Care Liaison (843) 792-
5555 concerning medical treatment. 
 
If I have any questions, problems, or concerns, desire further information or wish to offer input, I 
may contact the Medical University of SC Institutional Review Board for Human Research IRB 
Manager or the Office of Research Integrity Director at (843) 792-4148. This includes any questions 
about my rights as a research subject in this study. 
 
I agree to participate in this study. I have been given a copy of this form for my own records. 
 
Please sign below for paper consents or scroll to the bottom of the screen to provide an 
electronic signature. 
 
 
 
 
________________________________ 
Signature of Person Obtaining Consent 
Date 
*Name of Participant  
 
 


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Signature of Participant                              Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Prot_000.pdf: 
Version #7.0; Version Date: 10/28/2020 
 
Page 1 of 11 
 
PROTOCOL TITLE: 
Topical treatment for superficial disseminated actinic porokeratosis: A Single-blinded 
Comparison Between Lovastatin/Cholesterol and Lovastatin 
 
PRINCIPAL INVESTIGATOR: Dr. Dirk Elston 
 
NCT04359823 
 
 
 
 


Version #7.0; Version Date: 10/28/2020 
 
Page 2 of 11 
 
  
1.0 
Objectives / Specific Aims 
• 
The purpose of this study is to evaluate the effectiveness of cholesterol/lovastatin 
versus lovastatin alone to treat porokeratosis. Our working hypothesis is that both 
topical cholesterol/lovastatin and lovastatin alone are helpful in treating patients with 
disseminated superficial actinic porokeratosis (DSAP).  
• 
Aims: 
• 1. To evaluate the response to treatment with topical cholesterol/lovastatin and 
lovastatin alone in a series of patients with the diagnosis of DSAP. 
• 2. To characterize lesion patterns following topical treatment and patterns of lesion 
regression.  
 
2.0 
Background 
Porokeratosis is a premalignant condition with a malignant transformation rate of 7.5%1. 
Variants include disseminated superficial actinic porokeratosis (DSAP), disseminated 
superficial porokeratosis, porokeratosis of Mibelli, porokeratosis palmaris et plantaris 
disseminate, porokeratosis ptychotropica, and linear porokeratosis.  
Porokeratosis is a rare condition involving clonal proliferation of abnormal keratinocytes 
that can be inherited or acquired. DSAP is the most common type of porokeratosis. It is 
described as a well circumscribed, erythematous macule with a peripheral rim of 
hyperkeratosis, also referred to as the coronoid lamella. While typically benign, lesions 
may develop into squamous cell carcinoma or Bowen’s disease1.  The lesions typically 
spare the palms and soles and are most prevalent on the extensor surfaces and back. DSAP 
typically presents in patients in their 30s and 40s who have a history of extensive 
ultraviolet radiation exposure. It is estimated to occur in a female to male ratio of 1.8:12. 
The exact pathogenesis for DSAP is currently unknown, however, the mevalonate genetic 
pathways are suspected to play a role in development. In one study, at least one mutation 
in the mevalonate pathway was found in 98% of familial cases and 70% of sporadic cases3. 
Treatment usually consists of destruction of the lesion utilizing cryotherapy, photodynamic 
therapy, carbon dioxide lasers, 5-fluorouracil. However, recent observations have 
suggested that various porokeratosis variants arise in areas affected by second-hit 
mutations in genes encoding components of the mevalonate pathway. Consequently, 
investigators from Yale University successfully treated a series of patients with topical 
cholesterol/lovastatin which resulted in complete clearance of DSAP lesions after 4 weeks 
of treatment4. 
It is hypothesized that statins will block the accumulation of toxic metabolites in the 
mevalonate pathway, while topical cholesterol will provide the essential nourishment to 
the cells4.  This study will provide a larger sample size and allow us to observe more 
definitive outcomes of the stain/cholesterol therapy. 
 
3.0 
Intervention to be studied  
Noninvasive in vivo imaging techniques have become an important diagnostic aid for skin cancer 
detection. Dermoscopy, also known as dermatoscopy, epiluminescence microscopy, incident light 
microscopy, or skin surface microscopy, is performed using a handheld instrument called a 


Version #7.0; Version Date: 10/28/2020 
 
Page 3 of 11 
 
dermatoscope or dermoscope, which has a transilluminating light source and standard magnifying 
optics (10×). The dermatoscope facilitates visualization of subsurface skin structures located 
within the epidermis, dermoepidermal junction, and papillary dermis, which are otherwise 
invisible to the unaided eye. Colors and structures visible with dermoscopy are required for 
generating a correct diagnosis. 
 
Dermlite dermatoscopes are approved by the FDA.  
 
We will utilize 2% cholesterol and 2% lovastatin ointment. It will be compounded by a 
pharmacist. Ointment will be applied on lesional skin with occlusion twice daily. 
Cholesterol and lovastatin are not approved by the FDA to be used in porokeratosis but are 
used off-label by physicians for the treatment of DSAP. 
 
Pharmacology  
Cholesterol is an animal sterol found in the body tissues (and blood plasma) of vertebrates. 
It can be found in large concentrations within the liver, spinal cord, and brain. Cholesterol 
is an important component of the membranes of cells, providing stability. Cholesterol is 
distributed universally in all animal tissues. It can be derived either from intestinal 
absorption of dietary cholesterol or from synthesis de novo within the body. Cholesterol 
itself in the animal system is the precursor of bile acids, steroid hormones, and provitamin 
D3. 
 
Lovastatin is a lactone metabolite isolated from the fungus Aspergillus terreus with 
cholesterol-lowering and potential antineoplastic activities. Lovastatin is hydrolyzed to the 
active 
beta-hydroxyacid 
form, 
which 
competitively 
inhibits 
3-hydroxyl-3-
methylgutarylcoenzyme A (HMG-CoA) reductase, an enzyme involved in cholesterol 
biosynthesis. In addition, this agent may induce tumor cell apoptosis and inhibit tumor cell 
invasiveness, possibly by inhibiting protein farnesylation and protein geranylgeranylation, 
and may arrest cells in the G1 phase of the cell cycle. Studies suggest that less than 5% of 
the oral dose reaches the general circulation as active inhibitors and the time to peak serum 
concentration is 2-4 hours. Lovastatin undergoes extensive first-pass metabolism so the 
availability of the drug in the system is low and variable. The peak concentrations of 
lovastatin when a dose of 10-40 mg is administered are reported to range from 1.04-4.03 
ng/ml and an AUC of 14-53 ng.h/ml. This indicates that lovastatin presents a dose-
dependent pharmacokinetic profile.  
Lovastatin is a HMG-CoA reductase inhibitors that has been used topically for the 
treatment of skin disorders such as acne, seborrhoea, rosacea, rhinophyma, atopic 
dermatitis, contact dermatitis and ichthyosis (US Patent 5,730,992 1998 and US Patent 
6,126,947 2000). Topical lovastatin at 49 mM (20 mg/ml) in 95% ethanol is well-tolerated 
with limited side effects. Muscle breakdown may occur resulting in signs and symptoms 
such as myalgias, fasciculations, cramping, myopathy, rhabdomyolysis and increased 
levels creatine kinases in the blood. The ethanol component may induce mild skin dryness. 
It was effective in the treatment of acne vulgaris, thus supporting the expectation of 
absorption through the skin. Lovastatin is known to cause reversible cell cycle arrest and 
effective concentrations depend on cell type and experimental conditions, but cell culture 


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Page 4 of 11 
 
concentrations of 2 to 20 µM (0.8–8.0 µg/ml) for up to 72 h result in reversible cell cycle 
arrest with cells beginning to cycle after 6 hrs5,6.    
 
4.0 
Study Endpoints  
• 
Percentage of clearance of disseminated superficial actinic porokeratosis lesions after 
12 weeks of therapy 
• 
Validated scale changes: Patient Quality of Life (RAND36, DLQI), Physician Global 
Assessment Scale (DSAP-PGA), Actinic Keratosis Field Assessment Scale 
• 
Clearance of coronoid lamella on dermoscopy (or photograph) after 12 weeks of 
therapy.  
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 
Inclusion Criteria  
• 
All patients 18 years and older with the diagnosis of disseminated superficial 
actinic porokeratosis.  
Exclusion Criteria 
• 
Patients with allergies or contraindications to lovastatin or cholesterol 
• 
Female patients currently pregnant or lactating.  
• 
Patients requiring their medications to be delivered to Alabama (Chemistry Rx 
does not dispense medications to this state) 
• 
Female patients with plans to become pregnant. 
o Patients actively taking approved forms of long-term 
contraception (oral contraceptives, implantable intrauterine 
devices, or other hormone eluting implants) will be allowed 
to participate as long as they have no plan to become 
pregnant during the course of the study. A urine pregnancy 
test will be administered to these patients to confirm that 
they can be included in the study. 
6.0 
Number of Subjects 
Approximately 50 subjects will be recruited. 
7.0 
Setting 
• 
Study Sites  
• 
Virtual video chat forums with patients living in the USA. 
• 
Medical University of South Carolina  
! Dermatology Clinics 
 
 
8.0 
Recruitment Methods 


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Page 5 of 11 
 
Recruitment will occur after standard of care visits to the Dermatology Clinics, virtual 
visits, and chart review of eligible patients.  
For standard of care visits, the first person to tell eligible patients about this study will be 
someone directly involved in their patient care. If they are interested, the aforementioned 
clinician and study team members will approach the patients without coercion and with the 
emphasis on the voluntary aspect of being on this study. Subjects will also be told in a 
caring manner that no matter what their decision is, it will not affect how their doctor cares 
for them as a patient or their care in general.   
Patients discovered via chart review will be contacted to be informed of the potential 
research opportunity under the same aforementioned conditions. Only patients who have 
indicated they are willing to be contacted for research opportunities on their MUSC profile 
will be eligible for this form of contact. In this instance the first person to contact them 
may not be someone directly involved in their patient care.  
Potential subjects who contact the study team members directly will also be considered for 
participation in the study. In this event, these potential subjects must have heard about the 
study through indirect information sources (clinicaltrials.gov, DSAP support groups, or 
other means by which the study team members did not directly advertise the study for 
purposes of recruitment). If they are interested, the aforementioned study team members 
will respond to them via email, and subsequently approach the patients virtually without 
coercion and with the emphasis on the voluntary aspect of being on this study. Subjects 
will also be told in a caring manner that no matter what their decision is, it will not affect 
how their doctor cares for them as a patient or their care in general.   
 
 
9.0 
Consent Process 
Written informed consent will be obtained from subjects. Informed consent will be 
obtained in a private room within the clinics or privately via virtual visits. All subjects will 
undergo a prescreening call by study team members during which they are informed of the 
details of the study, eligibility concerns, and given the opportunity to ask and questions or 
address concern about the study. They will be sent the consent form immediately 
afterward, allowing them ample time to review the document before meeting the study 
team in person or virtually during visit 1 (week 0). During visit 1, the trained study team 
member performing consent will then review the consent form with them once again and 
address any questions before the sign the document and return it to the team via email. 
Virtual consenting will be performed on REDcap. Only trained research team members 
will be obtaining informed consent. Training will be performed by Alan Snyder and only 
those who are trained will perform informed consent after they sign the study training log. 
No waiting period will be necessary between informing the subjects and obtaining the 
consent; however, subjects will be allowed to take home the unsigned consent form for 
review prior to signing it if needed.  
The virtual consent process for patients who contact study team members directly about 
potential interest in participating is summarized below: 
1. subjects contact our study team after hearing about our study from indirect sources 
2. Interested subjects are called by one of our study team members for a prescreening call 
in which we determine if they are eligible to participate in our study. This is also an 


Version #7.0; Version Date: 10/28/2020 
 
Page 6 of 11 
 
opportunity for Q&A for potential participants who may want eligibility information or 
details about the study prior to an official enrollment visit. 
3. Potential subjects are securely emailed a copy of the IRB-approved ICF and scheduled 
for an official enrollment video visit that is mutually agreeable for the investigators and 
potential participant. The time period between this email and the enrollment visit will 
provide participants ample time to review the ICF in detail so that they have the 
opportunity to prepare additional questions during the official enrollment visit. 
4. Investigators and potential participants engage in a video chat for consenting, in which 
REDCap will be used for execution of the consent process. Study participants will have the 
option to have the signed ICF sent to their personal email after it is signed by both parties. 
6. Subsequently, Visit 1 will proceed following the procedures in our protocol  
 
10.0 Study Design / Methods 
• Potential subjects will be approached for informed consent as directed in sections 
8.0 and 9.0. Pertinent project information, risks, and time commitment will be 
relayed to subjects. If subjects show interest in participating, they will be given 
consent forms to either sign or bring home for consideration. A urine pregnancy 
test will be administered to these patients to confirm that they can be included in 
the study. 
• If the patient is eligible for the study, he or she will be randomly assigned to one of 
two groups. They will have a 50/50 chance of being in either group. Neither the 
researchers nor you will make the choice to which group you are assigned.  The 
two groups are Group A (cholesterol/lovastatin) and Group B (lovastatin only). The 
patient will not be informed of which group they are in and will not be informed of 
what their study medication is, allowing single-blinding. Researchers will not be 
masked. 
• Enrolled subjects will be followed up at monthly intervals for three months via 
virtual check-in using an MUSC approved HIPAA compliant technology. At each 
visit, participants will undergo brief, limited physical examination (in order to 
determine disease severity and affected body surface area); additionally, clinical 
photographs of the lesion will be obtained in clinic or shared virtually with the 
investigators via secure email (sent to MUSC Outlook email). The physical exam 
will occur in-person or by using the virtual visit technology, which allows us to see 
the patient and visualize their skin findings.. Photographs will be stored in the 
coded study-specific medical record for further analysis of lesion features.  
• At each visit a Patient Quality of Life, Physician Global Assessment Scale, and 
Actinic keratosis Field Assessment Scale will be administered.  
• Patients will be contacted via virtual check-in visits at weeks 4, 8, and 12. Patients 
will be asked about compliance and any adverse effects experienced. Patients are 
also encouraged to contact Alan Snyder at any given point during the study if they 
think they are experiencing study-related side effects. Immediate consultation will 
follow to determine the severity of such event and necessary impacts on patient 
health and participation. Participants will also be contacted by phone by study team 
member to assess for any adverse effects at weeks 2 and 6 of treatment. 


Version #7.0; Version Date: 10/28/2020 
 
Page 7 of 11 
 
• Compounded topical medication prescribed to subjects will be self-applied twice 
daily. These medications will be prepared by Tidewater Pharmacy in Mount 
Pleasant, SC or Chemistry Rx in Philidelphia, PA. They will be prepared so the 
study will remain single-blinded (only investigators know which study drug they 
are receiving) and associated costs will not be covered by the research budget. The 
cost of the medication will be approximately $85 when dispensed by Tidewater 
Pharmacy, or $110 when dispensed by Chemistry Rx. The differences in costs are 
attributed to shipping and pharmacy fees. 
• Both pharmacies will be compounding the drugs to be used in this study, and the 
compounding formula (recipe) will be identical between these two compounding 
pharmacies. 
• Enrollment and prescription drug delivery to other states will not be performed 
until the respective state pharmacy boards confirm the legality of clinical telehealth 
interventions and out-of-state pharmacy prescriptions. All state and federal 
guidelines will be followed according to their regulations and recommendations. 
• Patient prescriptions will be called in to their respective pharmacies by credentialed 
study team members after enrollment is completed. Individual prescriptions will be 
called in to the aforementioned pharmacies so that the pharmacies can individually 
ship the medication to the respective participant. Both pharmacies are well aware of 
the study protocol and procedures for sending the prescription. This will occur by 
standard procedure of calling medications for patients:  
! 1. The study team member will call the pharmacist to 
inform them that a participant has been enrolled and ready 
to receive one of the two single-blinded drugs. The 
lovastatin/cholesterol combination has been assigned the 
arbitrary codename “RDC100”, and the lovastatin alone 
medication has been assigned the arbitrary codename 
“RDC15”. On the prescription label there will be the 
codename, application instructions, and storage instructions. 
! 2. Per standard procedure of calling in a prescription, the 
study 
team 
member 
will 
verbally 
inform 
the 
Tidewater/Chemistry Rx pharmacist of the patient name, 
birthday, and phone number so that the medication can be 
prescribed and so that the patient can be contacted by the 
pharmacist for shipping and payment purposes.  
! 3. The pharmacist will contact the patient over the phone in 
order to complete the medication payment over the phone 
and to identify the address to which the medication will be 
sent to. 
! 4. The subject will inform the study team member upon 
receival of the medication, confirm that they received the 
correct, randomized medication.  
! 5. All of the information related to drug disposal and 
reception 
will 
be 
recorded 
on 
the 
coded 
Drug 
Accountability Sheet, which is located separately in the 
secure box drive. 


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Page 8 of 11 
 
• Medications will be able to be shipped to all continental US states by Chemistry 
Rx, except Alabama. This is because Chemistry Rx does not have the license to 
dispense to Alabama. Therefore, any participant reliant upon an Alabama address 
to receive their medication will not be allowed to participate in this study. 
• Dermoscopic and clinical photographs will be subsequently analyzed for the 
presence of cornoid lamella. The team will record any additional dermoscopic or 
clinicals feature that may arise during the analyses.  
• Frequency of dermoscopic and clinical features will be analyzed against clinical 
involution to find possible predictors.  
• Procedures during the day of imaging: 
The doctor will identify the lesion(s) that will be analyzed. 
The lesion(s) will be measured and clinical and dermoscopy photographs will be 
taken. Facial images might be taken to assess lesions on the head area.  
Schedule of events: 
Event 
Screening 
Baseline 
Visit 1 
Week 4 
(virtual) 
Week 8 
(virtual) 
Week 12 
(virtual) 
Informed consent 
X 
 
 
 
Eligibility Assessment 
X 
 
 
 
Demographics 
X 
 
 
 
Physical Examination 
X 
 
 
 
Clinical photograph & 
Scale (3x) administration 
X 
X 
X 
X 
Dermoscopic 
photograph 
X 
 
 
 
Adverse events 
monitoring 
X 
X 
X 
X 
 
11.0 Data Management  
• Continuous data will be summarized using descriptive statistics (number of 
values, means, standard deviation, median, minimum and maximum). 
Categorical data will be summarized using frequency tables (frequencies and 
percent). 


Version #7.0; Version Date: 10/28/2020 
 
Page 9 of 11 
 
• We are comparing before and after photographs from the same patient, hence 
we employ analysis by paired t-test to compare baseline data with data after 
treatment. 
• Coded dermoscopic and clinical photographs may be obtained for further 
analyses. Files with patient images will be stored in a secure departmental drive 
that will only be accessible to study team members by their unique MUSC ID 
and password. 
! Photos shared directly via email to study team members will be 
also be uploaded to the participants respective coded folder on 
the Box drive.  
! These emailed photos (sent by the participant personal email) 
must be de-identified close up photos of the participants legs or 
arms, and sent only to study team members secure MUSC-
assigned Outlook email addresses. Photos that do not fit this 
criteria will be deleted upon receival and not used in the study. 
• All subject medical record information and data collection will be coded and 
stored on an MUSC Box drive only accessible to study team members, and will 
be protected by two-factor authentication. 
12.0 Withdrawal of Subjects  
1. 
Any adverse effect during patient’s treatment will require a thorough review of the adverse 
event by the study team members. Depending on the severity of the adverse event, the 
participant may be recommended to withdrawal from the study. The research team will 
continue to follow the patient until resolution of said adverse event has resolved. 
2. 
Upon subject’s verbal notification, the study team will evaluate the adverse event, they will 
proceed to document it and evaluate for subject safety. They will determine if subject is 
suitable to continue in the study. 
3. 
Information will be provided about safe discontinuation of the drug and if any clinical 
review needs to occur. For evaluation and reporting purposes, researchers may conduct an 
exit interview and ask subjects about the reason for early withdrawal. 
4. 
Subjects can participate in the study as long as they want. Subjects may verbally notify 
investigators if they wish to voluntarily withdrawal from the study and they will be 
removed immediately. 
 
13.0 Risks to Subjects 
• We anticipate minimal side effects and local irritation to be minimal. Muscle toxicity is 
a known adverse effect of statins. Patients will be notified during enrollment to watch 
out for common signs and symptoms such myalgias, fasciculations, cramping, 
myopathy and increased levels of CK. If an adverse event occurs, the subject must 
notify the study team members at their earliest convenience. Upon the subject’s verbal 
notification to the study team, the study team will evaluate the adverse event and will 
proceed to document it and evaluate for subject safety. They will determine if subject is 
suitable to continue in the study. 


Version #7.0; Version Date: 10/28/2020 
 
Page 10 of 11 
 
• If there is an increased frequency of any concerning adverse event in particular, all 
enrolled participants in the trial will be sent an individual notice. 
• There is a risk for possible breach of confidentiality as photographs of face may be 
taken to assess lesions on the head. However, all measures to keep information 
protected will be taken.  
• There is a risk of emotional discomfort while the subject takes the questionnaires. 
• A cumulative data assessment will be conducted every other month throughout the 
study’s duration by study team members. A report that includes any available efficacy 
data, as well as a record of anticipated adverse events, will be compiled and submitted 
to the IRB at that time. Any event meeting the criteria of an unanticipated problem 
involving risks to subjects or others will be immediately reported to the MUSC IRB, as 
required by HRPP 4.7- Unanticipated Problems and Adverse Events Policy and 
Procedures.  
• The plan for subject safety and minimizing risks of the research is as follows: 
Inspection of the treatment site at each visit. Adverse effects of topical 
lovastatin/cholesterol will be specifically assessed at each research visit by the 
investigator, per outlined procedures. Participants are encouraged to reach out to the 
study coordinator if they think they are experiencing any adverse events. Other 
expected adverse effects deemed intolerable by the patient will prompt reduction in the 
patient’s dose and treatment if indicated. Any condition necessitating cessation of the 
study drug will be followed to resolution.  
• However, the side effect profile associated with both topical cholesterol and lovastatin 
is extremely small. We do not anticipate there being any complications associated with 
treatment other than minor, local irritation. The rare chance of developing stain induced 
myopathy and its associated signs and symptoms will be addressed during enrollment 
and each individual visit.    
 
14.0 Potential Benefits to Subjects or Others 
Patients will may benefit from the intervention. Researchers hope that the treatment 
will help clear active DSAP lesions, but all benefits are hypothetical currently. 
 
15.0 Sharing of Results with Subjects 
Results may be shared with subjects at the end of the study per verbal request.  
 
16.0 Drugs or Devices   
5. 
Drugs will be compounded by Tidewater Pharmacy or Chemistry Rx prior to the patients 
week 0 visit. They will be stored at this pharmacy until the subject is able to pick it up or 
have it delivered to their home address. 
6. 
Investigators will be in charge to handle dermoscope and will be responsible to upload the 
images to the secured folder. The Dermatoscope is device used SOC for analysis of DSAP 
lesions. 
7. 
An investigational drug exemption support document has been submitted to the eIRB. 
References 
1.  
Sasson M, Krain AD. Porokeratosis and cutaneous malignancy. A review. Dermatol Surg. 


Version #7.0; Version Date: 10/28/2020 
 
Page 11 of 11 
 
1996;22(4):339-342. doi:10.1111/j.1524-4725.1996.tb00327.x 
2. 
Sertznig, P., von Felbert, V. and Megahed, M. (2012), Porokeratosis: present concepts. Journal of 
the European Academy of Dermatology and Venereology, 26: 404-412. doi:10.1111/j.1468-
3083.2011.04275.x 
3. Zhang Z, Li C, Wu F, et al. Genomic variations of the mevalonate pathway in porokeratosis. Elife. 
2015;4:e06322. Published 2015 Jul 23. doi:10.7554/eLife.06322 
4.  
Atzmony L, Lim YH, Hamilton C, et al. Topical cholesterol/lovastatin for the treatment of 
porokeratosis: A pathogenesis-directed therapy. J Am Acad Dermatol. 2020;82(1):123-131. 
doi:10.1016/j.jaad.2019.08.043 
5.  
Jakóbisiak M, Bruno S, Skierski JS, Darzynkiewicz Z. Cell cycle-specific effects of lovastatin. 
Proc Natl Acad Sci U S A. 1991;88(9):3628-3632. doi:10.1073/pnas.88.9.3628 
6.  
Keyomarsi K, Sandoval L, Band V, Pardee AB. Synchronization of tumor and normal cells from 
G1 to multiple cell cycles by lovastatin. Cancer Res. 1991;51(13):3602-3609. 
http://www.ncbi.nlm.nih.gov/pubmed/1711413. 
 
 

SAP_001.pdf: 
Statistical Analysis Plan 
 DSAP: Single-Blinded randomized trial 
1/12/22 
 
 
Page 1 of 9 
 
Statistical Analysis Plan (SAP) 
The Safety and Efficacy of topical 2% Lovastatin/2% Cholesterol and topical 2% Lovastatin 
for the treatment of Disseminated Superficial Actinic Porokeratosis: A single-blinded 
randomized clinical trial 
 
Principal Investigator  
Dirk Elston, MD, Professor and Chairman of Department of 
Dermatology and Dermatologic Surgery 
Medical University of South Carolina 
Charleston, SC  
 
NCT ID number: 
 
NCT04359823 
 
 
Author  
Alex Drohan, MD  
Department of Dermatology and Dermatologic Surgery 
Medical University of South Carolina, Charleston, South 
Carolina  
 
Version Draft 0.1 
 
 


Statistical Analysis Plan 
 DSAP: Single-Blinded randomized trial 
1/12/22 
 
 
Page 2 of 9 
 


Statistical Analysis Plan 
 DSAP: Single-Blinded randomized trial 
1/12/22 
 
 
Page 3 of 9 
 
  
Abbreviations 
 
DSAP  
Disseminated Superficial Actinic Porokeratosis 
GASI  
General Assessment Severity Index 
ITT 
 
Intention to Treat 
PP 
 
Per Protocol 
 
 
 
 
 
 


Statistical Analysis Plan 
 DSAP: Single-Blinded randomized trial 
1/12/22 
 
 
Page 4 of 9 
 
Table of Contents 
1. Introduction........................................................................................................................... 5 
2. Study design ........................................................................................................................ 5  
2.1 Sample size calculation...................................................................................................... 7  
3. Aims and objectives.............................................................................................................. 7  
4. Outcomes ............................................................................................................................. 7  
4.1 Primary outcome................................................................................................................. 8 
4.2 Secondary outcomes........................................................................................................... 8 
4.3 Safety outcomes.................................................................................................................. 8 
5. Populations and subgroups to be analyzed ........................................................................... 8  
5.1 Populations.......................................................................................................................... 8  
5.2 Subgroups............................................................................................................................ 9 
6. Analyses................................................................................................................................ 9  
6.1 Primary outcome................................................................................................................. 8  
6.2 Secondary outcomes........................................................................................................... 8  
7. Missing data ......................................................................................................................... 9 
 
 
 
 


Statistical Analysis Plan 
 DSAP: Single-Blinded randomized trial 
1/12/22 
 
 
Page 5 of 9 
 
 
1 
Introduction 
The aim of this study is to test in a single-center randomized clinical trial, if topical 
statins combined with topical cholesterol can reduce the severity (size, color, quality 
of life impact) of disseminated superficial actinic vs statin therapy alone.  
This statistical analysis plan (SAP) will give more detailed descriptions of the 
endpoints in the study and the corresponding analysis.  
2 
Study Design 
Patients with previous diagnosis of DSAP will be approached for informed 
consent as directed in sections 8.0 and 9.0 of the protocol. If the patient is 
eligible for the study, he or she will be randomly assigned to one of two groups,  
Group A (cholesterol/lovastatin) and Group B (lovastatin only). The patient will 
not be informed of which group they are in and will not be informed of what 
their study medication is, allowing single-blinding. Researchers will not be 
masked. 
Enrolled subjects will be followed up at monthly intervals for three months via 
virtual check-in using an MUSC approved HIPAA compliant technology. At 
each visit, participants will undergo brief, limited physical examination (in 
order to determine disease severity and affected body surface area); 
additionally, clinical photographs of the lesion will be obtained in clinic or 
shared virtually with the investigators via secure email (sent to MUSC Outlook 
email). The physical exam will occur in-person or by using the virtual visit 
technology, which allows us to see the patient and visualize their skin findings. 
Photographs will be stored in the coded study-specific medical record for 
further analysis of lesion features.  
At each visit a Patient Quality of Life, Physician Global Assessment Scale, and 
RAND36 will be administered.  
Patients will be contacted via formal virtual visits at weeks 4, 8, and 12 and 
non-formal check-ins at weeks 2 and 6. Patients will be asked about compliance 
and any adverse effects experienced. Patients are also encouraged to contact 
Alan Snyder and/or Gabriella Santa Lucia at any given point during the study if 
they think they are experiencing study-related side effects. Immediate 
consultation will follow to determine the severity of such event and necessary 
impacts on patient health and participation. Non-formal check-ins will be done 
over phone by study team member to assess for any adverse effects at weeks 2 
and 6 of treatment. 
Compounded topical medication prescribed to subjects will be self-applied 
twice daily. These medications will be prepared by Tidewater Pharmacy in 
Mount Pleasant, SC or Chemistry Rx in Philidelphia, PA dependent upon 
patient geography. They will be prepared so the study will remain single-
blinded (only investigators know which study drug they are receiving) and 
associated costs will not be covered by the research budget. The cost of the 
medication will be approximately $85 when dispensed by Tidewater Pharmacy, 


Statistical Analysis Plan 
 DSAP: Single-Blinded randomized trial 
1/12/22 
 
 
Page 6 of 9 
 
or $110 when dispensed by Chemistry Rx. The differences in costs are 
attributed to shipping and pharmacy fees. 
Both pharmacies will be compounding the drugs to be used in this study, and 
the compounding formula (recipe) will be identical between these two 
compounding pharmacies. 
Enrollment and prescription drug delivery to other states will not be performed 
until the respective state pharmacy boards confirm the legality of clinical 
telehealth interventions and out-of-state pharmacy prescriptions. All state and 
federal guidelines will be followed according to their regulations and 
recommendations. 
Patient prescriptions will be called in to their respective pharmacies by 
credentialed study team members after enrollment is completed. Individual 
prescriptions will be called in to the aforementioned pharmacies so that the 
pharmacies can individually ship the medication to the respective participant. 
Both pharmacies are well aware of the study protocol and procedures for 
sending the prescription. This will occur by standard procedure of calling 
medications for patients:  
1. The study team member will call the pharmacist to inform them that a 
participant has been enrolled and ready to receive one of the two single-
blinded drugs. On the prescription label there will be a codename, application 
instructions, and storage instructions. 
2. Per standard procedure of calling in a prescription, the study team member 
will verbally inform the Tidewater/Chemistry Rx pharmacist of the patient 
name, birthday, and phone number so that the medication can be prescribed 
and so that the patient can be contacted by the pharmacist for shipping and 
payment purposes.  
3. The pharmacist will contact the patient over the phone in order to complete 
the medication payment over the phone and to identify the address to which 
the medication will be sent to. 
4. The subject will inform the study team member upon receival of the 
medication, confirm that they received the correct, randomized medication.  
5. All of the information related to drug disposal and reception will be 
recorded on the coded Drug Accountability Sheet, which is located separately 
in the secure box drive. 
Medications will be able to be shipped to all continental US states by Chemistry 
Rx, except Alabama. This is because Chemistry Rx does not have the license to 
dispense to Alabama. Therefore, any participant reliant upon an Alabama 
address to receive their medication will not be allowed to participate in this 
study. 
Dermoscopic and clinical photographs will be subsequently analyzed for the 
presence of cornoid lamella. The team will record any additional dermoscopic 
or clinicals feature that may arise during the analyses.  
Frequency of dermoscopic and clinical features will be analyzed against clinical 
involution to find possible predictors.  


Statistical Analysis Plan 
 DSAP: Single-Blinded randomized trial 
1/12/22 
 
 
Page 7 of 9 
 
Procedures during the day of imaging: 
The doctor will identify the lesion(s) that will be analyzed. 
The lesion(s) will be measured and clinical and dermoscopy 
photographs will be taken. Facial images might be taken to assess 
lesions on the head area.  
Schedule of events: 
Event 
Screenin
g 
Baseline 
Visit 1 
Wee
k 4 
(virt
ual) 
Wee
k 8 
(virt
ual) 
Week 
12 
(virtua
l) 
Informed 
consent 
X 
 
 
 
Eligibility 
Assessment 
X 
 
 
 
Demographics 
X 
 
 
 
Physical 
Examination 
X 
 
 
 
Clinical 
photograph & 
Scale (3x) 
administration 
X 
X 
X 
X 
Dermoscopic 
photograph 
X 
 
 
 
Adverse events 
monitoring 
X 
X 
X 
X 
 
 
2.1 
Sample Size Calculation 
DSAP is a rare disease that effects people from a wide geographical region. The goal sample 
size for the study was to recruit 50 subjects, however, due to recruiting limitations and state 
regulations, we were only able to enroll 31 patients. No formal sample size calculation was 
necessary as this study is first of its kind.  
 
 
3. Aims and Objectives 


Statistical Analysis Plan 
 DSAP: Single-Blinded randomized trial 
1/12/22 
 
 
Page 8 of 9 
 
• 
The purpose of this study is to evaluate the effectiveness of 
cholesterol/lovastatin versus lovastatin alone to treat porokeratosis. Our 
working hypothesis is that both topical cholesterol/lovastatin and 
lovastatin alone are helpful in treating patients with disseminated 
superficial actinic porokeratosis (DSAP).  
• 
Aims: 
• 1. To evaluate the response (lesion size, color, patient quality of life) to 
treatment with topical cholesterol/lovastatin and lovastatin alone in a 
series of patients with the diagnosis of DSAP. 
• 2. To characterize lesion patterns following topical treatment and 
patterns of lesion regression.  
• 3. Access quality of life outcomes through RAND36 and DLQI 
surveys.   
4. Outcomes 
This section will present the outcomes investigated to answer the study aims and objectives. 
The analyses are described in section 6 Analyses. 
4.1 Primary outcome 
Percentage of lesion clearance after 12 weeks of therapy using an exploratory clinical 
measure modified from a validated psoriasis index. The Disseminated Actinic Porokeratosis 
General Assessment Severity Index (DSAP-GASI) included plaque/rim elevation, scaling, 
and color (0= clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe).  
4.2 Secondary outcomes 
Self-reported evaluations (better, unchanged, worse) on overall appearance, color, scale, pain, 
and itch. Application frequency and consistency along with safety and tolerability were also 
assessed at each visit.  
Surveys: Patient quality of life measures, DLQI,and RAND36 
4.3 Safety Outcomes 
Adverse events  
Adverse events are reported at each clinic visit. Patients are also encouraged to 
contact Alan Snyder and/or Gabriella Santa Lucia at any given point during the study 
if they think they are experiencing study-related side effects. Immediate consultation 
will follow to determine the severity of such event and necessary impacts on patient 
health and participation. Participants will also be contacted by phone by study team 
member to assess for any adverse effects at weeks 2 and 6 of treatment. 
5. Populations and subgroups to be analyzed 
5.1 Populations 
Intention-to-treat (ITT) 
All randomized study subjects.  
Per Protocol (PP)  


Statistical Analysis Plan 
 DSAP: Single-Blinded randomized trial 
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All randomized study subjects completing the whole study period (complete cases). For a 
specific analysis, study subjects with missing data on any of the variables in the model will 
be excluded from the analysis. Analyses of this population is seen as a sensitivity analysis to 
investigate whether conclusions are sensitive to assumptions regarding the pattern of missing 
data.  
6. Analysis 
All enrolled subjects are considered in the demographic data and safety analysis. Treatment 
efficacy is based on investigator-standardized patient-documented photographs. Repeat photo 
documentation will be obtained if image quality was inadequate or angle, lighting or location 
is not standardized to prior photos.  
 
6.1 Primary outcome 
The primary analysis will compare the improvement in DSAP-GASI scores before treatment 
and after treatment in both groups. Only participants with clearly documented photos across 
all visits will be considered for the DSAP-GASI efficacy analysis. The scores will be graded 
by two blinded, trained physicians. Cronbach’s Interrater reliability will be calculated among 
raters across visits and the scores will be averaged for each of the four visits. Overall efficacy 
will be examined using a 2X4 (Drug X Time) Repeated Measures Analyses of Variance 
(ANOVA). The statin/cholesterol vs statin groups will be compared and evaluated for 
significant differences   
 
6.2 Secondary Outcomes 
Self-reported patient satisfaction on overall appearance, size, and color, will be 
recorded and examined using Chi-Square across drug for the final visit. Application 
frequency and safety may also be evaluated. 
A cross-sectional analysis of sociodemographic data and self-reported DSAP-related 
impact on QoL (scale 1-10) was averaged at baseline, while the RAND36 and 
Dermatology Life Quality Index (DLQI) were distributed and averaged at weeks 0, 4, 
8, and 12. Statistical measures used in analysis included a Repeated Measures 
Analyses of Variance (ANOVA) and Pearson correlation coefficient.  
7. Missing Data 
Patients who failed to submit photographs for the analysis will be removed from the DSAP-
GASI efficacy analysis. Missing data will be recorded and excluded from analysis.