Clinical trial NCT03643744
Conditions: Actinic Keratosis Photodynamic Therapy
Keywords: Actinic Keratosis Photodynamic Therapy
Sponsor: Wright State University
Start date: 2019-04-01; Completion date: 2023-03-21
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is designed as a double-blinded proof of concept of feasibility study to define if the immunosuppression associated with photodynamic therapy (PDT) can be blocked by treatment with cyclo-oxygenase-2 (COX-2) inhibitor celecoxib in comparison to placebo. PDT consists of application of the photosensitizer 5-aminolevulinic acid followed by treatment with a blue light. PDT is used to treat pre-cancerous actinic keratosis on large areas of skin. These studies are a continuation of ongoing studies that indicate that the lipid mediator platelet-activating factor (PAF) is generated in skin following PDT, and that PDT suppresses the immune system. It is hypothesized that PDT-generated PAF results in the immunosuppression associated with PDT. Therefore, it is proposed that a treatment to block that immunosuppression could protect the patient undergoing PDT. Blockers of the PAF system are not currently commercially available. However research studies done at Wright State University using mice indicate that PAF- and PDT-induced immunosuppression is blocked by treatment with COX-2 inhibitors. This study is conducted as a proof of concept.

Study length and visit for subjects with actinic keratoses: The first part of the study is completed in 12 days then there are follow up visits at 6 and 12 months. There are a total of 6 separate visits to the research office.

Study length and visit for control subjects: The study is completed in 10 days. There are a total of 4 separate visits to the research office.

Detailed description:

Arms: arm 1: Patient receiving PDT taking 200mg celecoxib. arm 2: Patient receiving PDT taking placebo. arm 3: Control subject not receiving PDT taking 200mg celecoxib. arm 4: Control subject not receiving PDT taking placebo.
Interventions: intervention 1: Celecoxib 200mg intervention 2: Placebo
Intervention descriptions: intervention 1: 14 Celecoxib 200mg taken 1 in the morning and 1 in the evening. intervention 2: 14 placebo capsules taken 1 in the morning and 1 in the evening.

Protocol documents:
ICF_000.pdf: 
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INFORMED CONSENT AND RESEARCH AUTHORIZATION 
Research Subjects
Photodynamic Therapy-Induced Immune Modulation: PART III
Jeffrey B. Travers, M.D., Ph.D.  Department of Pharmacology & Toxicology, WSU
       
Sponsor(s) name and address:  
WSU Department of Pharmacology and Toxicology
702 Health Sciences Bldg.
3640 Colonel Glenn Hwy.
Dayton, OH 45435
Site(s) where study is to be conducted:  
Wright State Physician’s Building 
725 University Blvd 
Dayton Ohio 45435
Phone number for subjects to call for questions:  (937) 775-2500
Introduction and Background Information
Your physician has ordered photodynamic therapy (PDT) for your pre-cancerous skin lesions called 
actinic keratosis (AK). Our previous studies have demonstrated that PDT can result in a decrease in 
the function of your immune system. This also happens to the immune system after sunlight or 
tanning bed exposure. This slight decrease in the immune system caused by PDT is not good.  We 
think that if we can stop this effect, we can make PDT work better to remove AKs.  This study is to 
test whether one week treatment of a non-steroidal anti-inflammatory drug (NSAID; includes 
medicines like Aspirin or Ibuprofen) called celecoxib can block the decreased immune responses 
associated with PDT.  Subjects for this study need to be aged 45 or older, fair-skinned and scheduled 
to receive PDT to control pre-cancerous skin growths. The study is taking place at the Dermatology 
clinic at the Wright State Physicians Building. It is conducted by Dr. Jeffrey Travers, Principal 
Investigator.  
Purpose
This study will test if treatment with celecoxib for one week after a standard PDT treatment results in 
less immunosuppression (decrease in the function of the immune system), as measured by skin 
testing and blood testing, compared to those subjects given a blank pill (placebo). Both you and the 
investigators will not know if you got celecoxib or blank pill. At the end of the study, you will know how 
you were treated. Effects on your immune system will be tested by urine collection, blood samples 
and skin allergy testing. This study requires 6 visits to the WSP building.
You may not participate if you have the following:

uncontrolled diabetes mellitus (sugar diabetes)
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
kidney problems

any serious health disorder that compromises your immune system or wound healing 
problems

abnormal scarring

are taking any medications that interact with sunlight

an allergy or abnormal response to any drugs like celecoxib including ibuprofen (Motrin), 
Naprosyn (Aleve), or aspirin

history of recent bleeding ulcer

a clotting problem

history of strokes or heart attack  
This study is not designed to test PDT, as we know it is effective for your skin condition.  This study is 
testing if celecoxib given for one week after PDT blocks the effects of PDT on your immune system.   
If you consent to take part you will be one of 24 subjects (12 getting celecoxib, 12 getting blank pill) 
undergoing PDT to greater than 5% of their skin surface area.  
Procedures
All study procedures will be done after discussing and obtaining your written informed consent to 
participate. The study procedures are detailed below:
DAY -2 Days prior to your PDT treatment  

Explanation of the study and informed consent obtained

Intended PDT treatment sites will be noted, photographed and recorded

Numbers of AKs will be counted and mapped on a diagram for future comparisons 

Injections of antigens at two sites on your inner forearm. The injections will be just under your 
skin like a TB skin test. These antigens are commercially available and are commonly used in 
allergic responses.
o
Before the injection, each site will be measured non-invasively

Calipers to measure skin thickness (or swelling)
o
You will receive 1  injection of 0.1 ml of Candida Antigen
o
You will receive 1 injection of 0.1 ml of Trichophyton antigen (these will be 
approximately 5 cm-or 1 ½ inches- apart).
o
You will receive 1 injection of 0.1 ml of saline (salt water as control). Photographs will 
be taken of the injection sites. It is expected that most individuals will react to at least 
one of these antigens with a small area of redness and swelling of skin (like a positive 
TB test in a patient who has been exposed to TB). This would be a positive response to 
the skin test.

Blood will be drawn (20 ml-or about 4 teaspoons) to look for cells that impact your immune 
system.
DAY 0 Day of your Photodynamic Therapy

Prior to your Photodynamic Therapy:
o
Your skin tests will be inspected and measured for thickness.
o
Photographs will be taken of the skin test sites.
o
Urine sample will be collected to look for elements linked to the effects of PDT on skin.
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
You will receive your PDT treatment that your physician has ordered. PDT is a standard 
treatment at the Wright State University Dermatology clinics and about 75-80 procedures are 
performed here annually.  You will sign a separate informed consent for the PDT therapy. 
You/your insurance company will be responsible for the cost as that treatment is not a part of 
these research procedures. 

Urine specimen (six) containers and a biohazard bag will be provided for your home use. 
Urine samples will be collected and placed into the biohazard bag and stored in the freezer. 
These will be returned at Day 7 study visit.

You will be given a dispenser with a 7 day supply of celecoxib or blank placebo pills to take 2 
times per day.  Your first pill will be right after the PDT treatment.
DAY 1-5 Urine Home Collection

8 hours after your PDT treatment

First morning urine

You will rate the pain associated with the PDT treatment on the Skin Pain Visual Analogue 
Scale (VAS). The scale will be 0 (no skin pain) to 10 (severe skin pain). 
DAY 7  

Urine samples are returned to the research office

Repeat Candida and Trichophyton and saline control Skin Testing x 2
o
Testing done on a site which was treated with PDT
o
Testing done on a site which was not treated with PDT

Blood will be drawn (20 ml-or about 4 teaspoons).

You will be asked to rate the pain in the PDT-treated sites (0-10).
DAY 9   

Candida/Trichophyton skin test results will be measured and photographed
   
6 Months and 12 Months Follow Up Visits  

Your current number and sites where you have precancerous AK lesions will be marked at 
your normally scheduled patient visits. These will be compared to your mapping obtained at 
the start of this study.  The comparison of AKs pre-treatment with post-treatment may help 
to define the effectiveness of your PDT treatment.  This information will become part of 
your medical record.
 
All study procedures will take place in the Department of Dermatology outpatient clinic at the Wright 
State Physician’s building.  Once study procedures are completed you will not have to complete 
anymore study visits or procedures. Also, no further follow up will be required for this study.  We of 
course encourage you to keep your regular follow-up dermatology clinic appointments if you and your 
dermatologist feel they are needed.  
Biospecimen Sampling for Research:
Research using biospecimens (saliva, blood, tissues, etc.) is an important way to try to understand 
human disease and functioning.  There are several things you should know before allowing your 
biospecimens to be studied.
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The type of specimens that will be stored and where they will be stored: Blood and urine samples will 
be stored at Dr. Travers’ laboratory on the Wright State University Campus.   
Identifiability of Biospecimens: The samples will be coded by study number XXXXX followed by 
subject number 001, 002, 003, etc.  
The length of time your biospecimen will be stored until they are destroyed: Your samples will be 
stored until the analyses are completed. At that time, they will be destroyed.
How to withdraw your biospecimens from the study: 
Because your samples will not be linked to your name after they are stored, you cannot withdraw your 
consent to the use of the samples after they are taken.
Future Use of Biospecimens:
Information or specimens for this research may be used for future research studies or shared with 
other researchers for future research.  If this happens, any information which could identify you will be 
removed before any information or specimens are shared.  Since identifying information will be 
removed, we cannot ask for your additional consent. 
Risks
While on the study, the risks are:
Photography - The risk of photography is the possible loss of privacy.  Pictures will not be of 
recognizable body parts or markings. Photos will be labeled with the study number and a code that 
does not identify you.  Photos will not include any identifying information.  
Photodynamic therapy- The risk of the PDT treatments that your dermatologist recommends for you 
will be discussed between you and your treating physician. The informed consent your physician will 
provide for you will detail the potential side effects of that treatment.   
Skin immune testing – The Candida and Trichophyton skin testing usually results in a small area of 
inflammation.  This will last for a few days then resolve.  Rarely, a more significant reaction with even 
a widespread rash has been reported.  However, any long-term effects are not expected. If you do 
experience a greater than normal reaction, we will not repeat its use with you.  These skin testing 
protocols are commonly used and have been considered as safe procedures to test for allergies and 
inflammatory responses. 
Celecoxib treatment – Celecoxib works like Ibuprofen (Motrin) and Naprosyn (Aleve), however, it is 
not associated with stomach upset like Ibuprofen and Naprosyn. Long-term treatment (months to 
years) with celecoxib could result in increased risks of clotting issues like heart attacks and strokes.  
However, the one week treatment we plan should not have this effect. If you have any kidney 
problems or have any allergies or sensitivities to these drugs you cannot take part in this study.     
Urine testing – This does not have any side effects.
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Steps Taken to Reduce Risk of Coronavirus Infection
The following steps are being taken to address the risk of coronavirus infection: 
Screening: If you show potential symptoms of COVID-19 (fever, cough, shortness of breath, etc.), 
you will NOT be permitted to participate in this study at this time. Our study team is required to show 
no potential symptoms of COVID-19 prior to reporting to work.
Physical distancing: Whenever possible, we will maintain at least 6 feet of distance from you while 
conducting the study. 
Mask/Covering: You and our study team are required to wear a cloth face cover or mask that covers 
the mouth and nose during the study, even when maintaining at least 6 feet of distance. If you do not 
have a mask, one will be provided when entering the building. Tissues will be available to cover 
coughs and sneezes.
Handwashing: You and our study team will wash hands before/during examination or use a hand 
sanitizer. 
Disinfecting materials: When feasible, we will clean and disinfect surfaces between participants, 
using an EPA-registered disinfectant for hard materials and by laundering soft materials. Disinfected 
materials will be handled using gloves, paper towel, plastic wrap or storage bags to reduce the 
chance of re-contamination of materials.
Electronics: Alcohol-based wipes or sprays will be used to disinfect shared touch screens, mice, 
keyboards, etc. Surfaces will be dried to avoid pooling of liquids.
Benefits of Taking Part in the Study
There are no direct benefits to participating in this study.  There are possible indirect benefits 
such as:

The research studies could result in a better understanding of PDT effects on the 
immune system.

A possible treatment to improve the effectiveness of this treatment.  
Moreover, our plans to keep track of the AKs on your skin could assist your dermatologist in 
managing these pre-cancerous lesions. 
Research Subject Costs 
There will be no costs to you for any of the treatment or testing done as part of this research study.  
This study does not pay for the PDT treatment that you and your dermatologist have determined is 
the best treatment for your AKs. PDT treatment is your routine, standard care and not part of 
research. The research is looking at the potential effects of PDT treatment.
Compensation & Treatment for Injury 
You will be compensated for your participation and completion of study visits.  
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 Breakdown for each event is as follows:
Consent
$20.00  
PDT ($20) 
Venipuncture
$10.00  
PDT ($20) 
Urine collection
$5.00  
PDT ($35) 
Skin testing APPLICATION
$15.00  
PDT ($45) 
Skin testing READING
$20.00  
PDT ($40) 
Bonus for completing study 
$65.00  
PDT ($65) 
Follow up visits at 6 and 12 months
$25.00  
PDT ($50) 
If you complete all study visits, you will receive a maximum of $275.00.  Compensation is based upon 
completed study visits and overall study completion. There is no cost for parking at the Wright State 
Physician’s Building.  
If you are hurt by being in this research study, medical treatment will be arranged for you.  Dr. Travers 
will provide care at no cost to you, although you may have a pharmacy fee if any prescriptions are 
needed. You do not give up your legal rights by signing this form.  If you think you have a research 
related injury, please call the investigator at (937) 775-2463 or 775-2500. In addition, you may suffer 
harms that we have not seen before. 
Confidentiality
Total privacy cannot be guaranteed.  We will protect your privacy to the extent permitted by law.  If 
the results from this study are published, your name will not be made public. Once your information 
leaves our institution, we cannot promise that others will keep it private.  
Identifiers might be removed from your identifiable private information (or/and identifiable 
biospecimens). After such removal, the information or biospecimens could be used for future 
research studies or distributed to another investigator for future research studies without your (or your 
legally authorized representative’s) consent.
Data Security 
Data will be kept in locked cabinets in a locked room in the WSP Building or in a password-protected 
computer in the WSU Department of Pharmacology & Toxicology.
Voluntary Participation
Taking part in this study is completely voluntary. You may choose not to take part.  If you decide not 
to be in this study, you won’t be penalized or lose any benefits for which you qualify. If you decide to 
be in this study, you may change your mind and stop taking part at any time. If you decide to stop 
taking part, you won’t be penalized or lose any benefits for which you qualify.  You will be told about 
any new information learned during the study that could affect your decision to continue in the study.
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Termination
The investigator, the IRB or the study sponsor has the right to stop this study at any point.  The 
investigator may take you out of this study with or without your permission.  Reasons why this may 
occur include: 

Pregnancy

Onset of diabetes

The need to take a medicine that reacts with sunlight  
Your Rights/Responsbilities As A Research Subject
As a subject, your responsibilities include: 

Follow the instructions of the research study staff.

Keep your study appointments.  If it is necessary to miss an appointment, please contact the 
research study staff to reschedule as soon as you know you will miss the appointment.

Tell the research study staff about any side effects, doctor visits, or hospitalizations that you 
may have.

Tell the research staff if you believe you might be pregnant.

Ask questions as you think of them.

Tell the research staff if you change your mind about staying in the study.
You may take part in this study if you are currently in another research study.  It is important to let the 
investigator know if you are in another research study.
Research Subject’s Rights, Questions, Concerns, and Complaints
If you have any questions, concerns, or complaints about the research study you may contact the 
principal investigator Dr. Travers or the research office at 937-775-2500.  
If you have any questions about your rights as a study subject, questions, concerns or complaints, 
you may call the Wright State IRB Office (937) 775-4462 or irb-rsp@wright.edu.  You may discuss 
any questions about your rights as a subject with a member of the IRB or staff.  The IRB is an 
independent group of members from the University community, staff of the institutions, as well as lay 
members of the community not connected with these institutions.  The IRB has reviewed this study.
  
Authorization to Use and Disclose Your Health Information
State and Federal laws, including the Health Insurance Portability and Accountability Act (HIPAA), 
require researchers to protect the privacy of your health information. This section of the consent form 
describes how researchers, with your authorization (permission), may use and release (disclose or 
share) your protected health information (PHI) for this research study. Please read this section of 
the consent form carefully. 
If you sign this document, you give permission to Dr. Travers and his Wright State Physicians 
Pharmacology Translational Unit research team to use or disclose (release) the following protected 
health information: 
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
Your medical records for past medical conditions and medications related to your health

All information (research records and medical records) created during your participation in 
this research study
The research team needs this information to conduct the study.  This study is testing whether a non-
steroidal anti-inflammatory drug (NSAID), celecoxib, treatment can block the decreases in immune 
system. 
To maintain the integrity of this research, you might not have access to any health information 
developed as part of this study until it is completed.  At that point, you generally would have access to 
your health information.
Disclosure of your protected health information 
 
If you sign this form, the researchers may share your health information during the conduct of the 
study with: 

Non-Wright State Physicians researchers or organizations working with Wright State 
Physicians researchers.

Law enforcement or other agencies, when required by law

WSU’s Institutional Review Board (or other IRB of record), which oversees our research 

The sponsor (the organization paying for) of this research study: National Institutes of 
Health (NIH)

Representatives of government agencies in the United States and other countries (i.e. 
Food and Drug Administration and the Office of Human Research Protection)

Other authorized Wright State University/Physicians Officials who oversee research and 
clinical care
  
The people listed above will use and share your health information to review the quality, safety, and 
results of the research and may also do additional research.
Please understand that these persons/organizations who may receive your health information may 
not be required by U.S. Federal privacy laws (such as HIPAA) to protect it and may share your 
information with others without your permission. 
This authorization does not have an expiration date.
However, you can change your mind and cancel this authorization at any time. To cancel this 
authorization, you must write the study investigator listed at the beginning of this consent form.
 
If you cancel this authorization, you will no longer be allowed to take part in the research study.  If you 
cancel this authorization, health information you had already allowed us to obtain may still be used 
and disclosed by researchers in order to maintain the integrity and reliability of the research, and to 
report any adverse (bad) effects that may have happened to you. 
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Right to refuse to sign this Authorization 
 
You have the right to refuse to sign and give your authorization. If you do not sign this form, your non-
research related treatment, payment or enrollment in any health plans, or your eligibility for other 
medical benefits at Wright State Physicians will not be affected in any way.  
However, if you do not sign this form, you will not be able to participate in this research study.  
Signature of Subject
I have read (or someone has read to me) the above information.  I have been given an opportunity to 
ask questions and my questions have been answered to my satisfaction.  I agree to participate in this 
research and authorize the use and disclosure of my protected health information for this study.  I will 
be given a copy of this signed and dated form.
__________________
__
Signature
Date
__________________
Printed Name
________________________                  _____________
Signature of Person Obtaining Consent and Authorization                  Date 
______________________
_
Printed Name of Person Obtaining Consent and Authorization
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ICF_001.pdf: 
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INFORMED CONSENT AND RESEARCH AUTHORIZATION 
Control Subjects
Photodynamic Therapy-Induced Immune Modulation: PART III
Jeffrey B. Travers, M.D., Ph.D.  Department of Pharmacology & Toxicology, WSU
       
Sponsor(s) name and address:  
WSU Department of Pharmacology and Toxicology
702 Health Sciences Bldg.
3640 Colonel Glenn Hwy.
Dayton, OH 45435
Site(s) where study is to be conducted:  
 
Wright State Physician’s Building 
725 University Blvd 
Dayton Ohio 45435
Phone number for subjects to call for questions:  (937) 775-2500
Introduction and Background Information
Photodynamic therapy (PDT) treats areas of the skin that can turn into skin cancer.  Past studies 
have shown that PDT can decrease the function of the immune system. The same thing happens to 
the immune system after sunlight or tanning bed exposure. This slight decrease in the immune 
system caused by PDT is not good. We think that if we can stop this effect, we can make PDT work 
better to remove the potential skin cancer areas. This study is testing whether a non-steroidal anti-
inflammatory drug (NSAID), celecoxib, treatment can block the decreases in immune system. A 
NSAID is a drug like Aspirin or Motrin that is commonly used to treat pain and headaches.  This 
study requires subjects who are not undergoing Photodynamic Therapy.  Control subjects for 
this study need to be aged 45 or older and fair-skinned. The study is taking place at the Dermatology 
clinic at the Wright State Physicians Building. It is conducted by Dr. Jeffrey Travers, Principal 
Investigator.  
Purpose
This study will test if treatment with celecoxib for one week affects immunosuppression decreases in 
the function of the immune system), as measured by skin testing and blood testing, compared to 
those subjects given a blank pill (placebo). Both you and the investigators will not know if you got 
celecoxib or blank pill. At the end of the study, you will know how you were treated. Effects on your 
immune system will be tested by urine collection, blood samples and skin allergy testing. This study 
requires 4 visits to the WSP building.
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You may not participate if you have the following:

Uncontrolled diabetes mellitus (sugar diabetes)

Kidney problems

Any serious health disorder that compromises your immune system or wound healing 
problems

Abnormal scarring

Are taking any medications that interact with sunlight.  

An allergy or abnormal response to any drugs like celecoxib including ibuprofen (Motrin), 
Naprosyn (Aleve), or aspirin  

A clotting problem 

History of strokes or heart attack  
If you consent to take part you will be one of 24 subjects (12 getting celecoxib, 12 getting blank pill). 
Control data will consist of urine collection, blood samples and skin allergy testing.
Procedures
All study procedures will be done after discussing and obtaining your written informed consent to 
participate. The study procedures are detailed below:
DAY 0   

Explanation of the study and informed consent obtained

Injections of antigens at two sites on your inner forearm. The injections will be just under 
your skin like a TB skin test. These antigens are commercially available and are commonly 
used in allergic responses. 
o
Before the injection, each site will be measured non-invasively

Calipers to measure skin thickness (or swelling)
o
You will receive 1 injection of 0.1 ml of Candida antigen
o
You will receive 1 injection of 0.1ml of Trichophyton antigen (these will be about 5 
cm-or 1 ½ inches- apart).
o
You will receive 1 injection of 0.1ml of saline (salt water as control)
o
Photographs will be taken of the injection sites
It is expected that most individuals will react to at least one of these antigens with a 
small area of redness and swelling of skin (like a positive TB test in a patient who 
has been exposed to TB). This would be a positive response to the skin test.

Blood will be drawn (20 ml-or about 4 teaspoons) to look for cells that impact your immune 
system.

Urine specimen (six) containers and a biohazard bag will be provided for your home use. 
Urine samples will be collected and placed into the biohazard bag and stored in the 
freezer. These will be returned at Day 9 study visit.
DAY 2 

Candida/Trichophyton skin test results will be measured and photographed

You will be given a dispenser with a 7 day supply of celecoxib or blank placebo pills to take 
2 times per day. Starting today, you will take 1 pill in the morning and 1 pill in the evening. 
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DAY 2-7 Urine Home Collection

First morning urine 
DAY 9  

Urine samples are returned to the research office

Return pill dispenser

Repeat Candida and Trichophyton and saline control Skin Testing x 2 sites
o
Testing done on a site which is commonly treated with PDT (outer forearm, scalp)
o
Testing done on a site which is never treated with PDT (inner forearm)

Blood will be drawn (20 ml-or about 4 teaspoons).
DAY 11   

Candida/Trichophyton skin test results will be measured and photographed
 
All study procedures will take place in the Department of Dermatology outpatient clinic at the Wright 
State Physician’s building.  Once study procedures are completed you will not have to complete 
anymore study visits or procedures. Also, no further follow up will be required for this study.  We of 
course encourage you to keep your regular follow-up dermatology clinic appointments if you and your 
dermatologist feel they are needed.  
Biospecimen Sampling for Research:
Research using biospecimens (saliva, blood, tissues, etc.) is an important way to try to understand 
human disease and functioning.  There are several things you should know before allowing your 
biospecimens to be studied.
The type of specimens that will be stored and where they will be stored: Urine samples will be stored 
at Dr. Travers’ laboratory on the Wright State University Campus.   
Identifiability of Biospecimens: The samples will be coded by study number XXXXX followed by 
subject number 001, 002, 003, etc.  
The length of time your biospecimen will be stored until they are destroyed: Your samples will be 
stored until the analyses are completed. At that time, they will be destroyed.
 
How to withdraw your biospecimens from the study: 
Because your samples will not be linked to your name after they are stored, you cannot withdraw your 
consent to the use of the samples after they are taken.
Future Use of Biospecimens:
Information or specimens for this research may be used for future research studies or shared with 
other researchers for future research.  If this happens, any information which could identify you will be 
removed before any information or specimens are shared.  Since identifying information will be 
removed, we cannot ask for your additional consent. 
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Risks 
While on the study, the risks are:
Photography - the risk of photography is the possible loss of privacy.  Pictures will not be of 
recognizable body parts or markings. Photos will be labeled with the study number and a code that 
does not identify you.  Photos will not include any identifying information.    
Skin immune testing – The Candida and Trichophyton skin testing usually results in a small area of 
inflammation.  This will last for a few days then resolve.  Rarely, a more significant reaction with even 
a widespread rash has been reported.  However, any long-term effects are not expected.  If you do 
experience a greater than normal reaction, we will not repeat its use with you.  These skin testing 
protocols are commonly used and have been considered as safe procedures to test for allergies and 
inflammatory responses. 
Celecoxib treatment – Celecoxib works like Ibuprofen (Motrin) and Naprosyn (Aleve) however, it is 
not associated with stomach upset like Ibuprofen and Naprosyn. Long-term treatment (months to 
years) with celecoxib could result in increased risks of clotting issues like heart attacks and strokes.  
However, the one week treatment we plan should not have this effect. If you have any kidney 
problems or have any allergies or sensitivities to these drugs you cannot take part in this study.     
Urine testing – This test does not have any side effects. 
Steps Taken to Reduce Risk of Coronavirus Infection
The following steps are being taken to address the risk of coronavirus infection: 
Screening: If you show potential symptoms of COVID-19 (fever, cough, shortness of breath, etc.), 
you will NOT be permitted to participate in this study at this time. Our study team is required to show 
no potential symptoms of COVID-19 prior to reporting to work.
Physical distancing: Whenever possible, we will maintain at least 6 feet of distance from you while 
conducting the study. 
Mask/Covering: You and our study team are required to wear a cloth face cover or mask that covers 
the mouth and nose during the study, even when maintaining at least 6 feet of distance. If you do not 
have a mask, one will be provided when entering the building. Tissues will be available to cover 
coughs and sneezes.
Handwashing: You and our study team will wash hands before/during examination or use a hand 
sanitizer. 
Disinfecting materials: When feasible, we will clean and disinfect surfaces between participants, 
using an EPA-registered disinfectant for hard materials and by laundering soft materials. Disinfected 
materials will be handled using gloves, paper towel, plastic wrap or storage bags to reduce the 
chance of re-contamination of materials.
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Electronics: Alcohol-based wipes or sprays will be used to disinfect shared touch screens, mice, 
keyboards, etc. Surfaces will be dried to avoid pooling of liquids.
Benefits of Taking Part in the Study
There are no direct benefits to participating in this study.  There are possible indirect benefits 
such as:

The research studies could result in a better understanding of PDT effects on the 
immune system

A possible treatment to improve the effectiveness of this treatment.  
Research Subject Costs 
There will be no costs to you for any of the treatment or testing done as part of this research study.  
The research is looking at the potential effects of PDT treatment. You are asked to be a part of this 
study as a person who is NOT receiving PDT.
Compensation & Treatment for Injury
 
You will be paid for your participation and completion of study visits.  
Breakdown for each event is as follows:
Total
Consent
$20.00  
($20) 
Venipuncture
$10.00  
($20) 
Urine collection
$5.00  
($35) 
Skin testing APPLICATION
$15.00  
($45) 
Skin testing READING
$20.00  
($40) 
Bonus for completing study 
$65.00  
($65) 
If you complete all study visits, you will receive a maximum of $225.00.  Compensation is based upon 
completed study visits and overall study completion. There is no cost for parking at the Wright State 
Physician’s Building.  
If you are hurt by being in this research study, medical treatment will be arranged for you.  Dr. Travers 
will provide care at no cost to you, although you may have a pharmacy fee if any prescriptions are 
needed.   You do not give up your legal rights by signing this form.  If you think you have a research 
related injury, please call the investigator at (937) 775-2500 or 775-2463. In addition, you may suffer 
harms that we have not seen before. 
Confidentiality
Total privacy cannot be guaranteed.  We will protect your privacy to the extent permitted by law.  If 
the results from this study are published, your name will not be made public. Once your information 
leaves our institution, we cannot promise that others will keep it private.  
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Identifiers might be removed from your identifiable private information (or/and identifiable 
biospecimens). After such removal, the information or biospecimens could be used for future 
research studies or distributed to another investigator for future research studies without your (or your 
legally authorized representative’s) consent.
Data Security 
Data will be kept in locked cabinets in a locked room in the WSP Building or in a password-protected 
computer in the WSU Department of Pharmacology & Toxicology.
Voluntary Participation
Taking part in this study is completely voluntary. You may choose not to take part. If you decide not to 
be in this study, you won’t be penalized or lose any benefits for which you qualify. If you decide to be 
in this study, you may change your mind and stop taking part at any time. If you decide to stop taking 
part, you won’t be penalized or lose any benefits for which you qualify.  You will be told about any 
new information learned during the study that could affect your decision to continue in the study.
Termination
The investigator, the IRB or the study sponsor has the right to stop this study at any point.  The 
investigator may take you out of this study with or without your permission.  Reasons why this may 
occur include: 

Pregnancy

Onset of diabetes

The need to take a medicine that reacts with sunlight  
Your Rights/Responsibilities as A Research Subject
As a subject, your responsibilities include: 

Follow the instructions of the research study staff.

Keep your study appointments.  If it is necessary to miss an appointment, please contact the 
research study staff to reschedule as soon as you know you will miss the appointment.

Tell the research study staff about any side effects, doctor visits, or hospitalizations that you 
may have.

Tell the research staff if you believe you might be pregnant.

Ask questions as you think of them.

Tell the research staff if you change your mind about staying in the study.
You may take part in this study if you are currently in another research study.  It is important to let the 
investigator know if you are in another research study.
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Research Subject’s Rights, Questions, Concerns, and Complaints
If you have any questions, concerns, or complaints about the research study you may contact the 
principal investigator Dr. Travers or the research office at 937-775-2500.  
If you have any questions about your rights as a study subject, questions, concerns or complaints, 
you may call the Wright State University Institutional Review Board (IRB) at (937) 775-4462 or irb-
rsp@wright.edu.  You may discuss any questions about your rights as a subject with a member of the 
IRB or staff.  The IRB is an independent group of members from the University community, staff of 
the institutions, as well as lay members of the community not connected with these institutions.  The 
IRB has reviewed this study.
  
Authorization to Use and Disclose Your Health Information
State and Federal laws, including the Health Insurance Portability and Accountability Act (HIPAA), 
require researchers to protect the privacy of your health information. This section of the consent form 
describes how researchers, with your authorization (permission), may use and release (disclose or 
share) your protected health information (PHI) for this research study. Please read this section of 
the consent form carefully. 
If you sign this document, you give permission to Dr. Travers and his Wright State Physicians 
Pharmacology Translational Unit research team to use or disclose (release) the following protected 
health information: 

Your medical records for past medical conditions and medications related to your health

All information (research records and medical records) created during your participation in 
this research study
The research team needs this information to conduct the study.  This study is testing whether a non-
steroidal anti-inflammatory drug (NSAID), celecoxib, treatment can block the decreases in immune 
system. 
To maintain the integrity of this research, you might not have access to any health information 
developed as part of this study until it is completed.  At that point, you generally would have access to 
your health information.
Disclosure of your protected health information 
 
If you sign this form, the researchers may share your health information during the conduct of the 
study with: 

Non-Wright State Physicians researchers or organizations working with Wright State 
Physicians researchers.

Law enforcement or other agencies, when required by law

WSU’s Institutional Review Board (or other IRB of record), which oversees our research 
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
The sponsor (the organization paying for) of this research study: National Institutes of 
Health (NIH)

Representatives of government agencies in the United States and other countries (i.e. 
Food and Drug Administration and the Office of Human Research Protection)

Other authorized Wright State University/Physicians Officials who oversee research and 
clinical care
  
The people listed above will use and share your health information to review the quality, safety, and 
results of the research and may also do additional research.
Please understand that these persons/organizations who may receive your health information may 
not be required by U.S. Federal privacy laws (such as HIPAA) to protect it and may share your 
information with others without your permission. 
This authorization does not have an expiration date.
However, you can change your mind and cancel this authorization at any time. To cancel this 
authorization, you must write the study investigator listed at the beginning of this consent form.
 
If you cancel this authorization, you will no longer be allowed to take part in the research study.  If you 
cancel this authorization, health information you had already allowed us to obtain may still be used 
and disclosed by researchers in order to maintain the integrity and reliability of the research, and to 
report any adverse (bad) effects that may have happened to you.
Right to refuse to sign this Authorization 
 
You have the right to refuse to sign and give your authorization. If you do not sign this form, your non-
research related treatment, payment or enrollment in any health plans, or your eligibility for other 
medical benefits at Wright State Physicians will not be affected in any way.  
However, if you do not sign this form, you will not be able to participate in this research study.  
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Signature of Subject
I have read (or someone has read to me) the above information.  I have been given an opportunity to 
ask questions and my questions have been answered to my satisfaction.  I agree to participate in this 
research and authorize the use and disclosure of my protected health information for this study.  I will 
be given a copy of this signed and dated form.
___________________
__
Signature
Date
___________________
Printed Name
________________________                  _____________
Signature of Person Obtaining Consent and Authorization                  Date 
______________________
_
Printed Name of Person Obtaining Consent and Authorization
Approved
17-May-2021 
Expires
16-May-2022

Prot_SAP_002.pdf: 
 
 
 
Title: Photodynamic Therapy-Induced Immune Modulation: Part III 
NCT#: NCT03643744 
Document Date: 21Apr2021 


 
 
 
 
 
 
 
 
 
 
Photodynamic Therapy-Induced Immune 
Modulation: PART III 
 
PI: Jeffrey B. Travers, M.D., Ph.D. 
 
Department of Pharmacology & Toxicology 
Department of Dermatology 
Staff Physician, Dayton VAMC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Version 4.0 21Apr2021 
 
1 
 
 
 
Table of Contents: 
 
Study Schema 
1.0 
Background 
2.0 
Rationale and Specific Aims 
3.0 
Inclusion/Exclusion Criteria 
4.0 
Enrollment 
5.0 
Study Procedures/compensation 
6.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to 
Participants or Others 
7.0 
Study Withdrawal/Discontinuation 
8.0 
Statistical Considerations 
9.0 
Privacy/Confidentiality Issues 
10.0 Quality Control 
11.0 Follow-up and Record Retention 
12.0 COVID-19 Safety Plan 
13.0 References 
14.0 Abbreviations 
 


Version 4.0 21Apr2021 
 
2 
 
1.0 
Background 
 
This study is Part III of the Photodynamic Therapy-Induced Immune Modulation 
research. Part III is designed as a double-blinded proof of concept of feasibility study to 
define if the immunosuppression associated with photodynamic therapy (PDT) can be 
blocked by treatment with cyclo-oxygenase-2 (COX-2) inhibitor celecoxib in comparison 
to placebo.  PDT consists of application of the photosensitizer 5-aminolevulenic acid 
followed by treatment with a blue light.  PDT is used to treat pre-cancerous actinic 
keratosis on large areas of skin [1].  These studies are a continuation of ongoing studies 
that indicate that the lipid mediator platelet-activating factor (PAF) is generated in skin 
following PDT, and that PDT suppresses the immune system.  Our hypothesis is that 
PDT-generated PAF results in the immunosuppression associated with PDT.   
Therefore, we propose that a treatment to block that immunosuppression could protect 
the patient undergoing PDT. Unfortunately, blockers of the PAF system are not currently 
commercially available. However our research studies using mice indicate that PAF- and 
PDT-induced immunosuppression is blocked by treatment with COX-2 inhibitors (2,3). 
We would like to conduct this research study as a proof of concept.  
 
This double-blinded placebo-controlled study will test if a seven day treatment with COX-
2 inhibitor celecoxib (200mg BID) following PDT will 1) block PDT-induced 
immunosuppression, and 2) enhance the effectiveness of PDT as measured by 
decreased numbers of actinic keratosis at 6 months and 12 months following PDT in 
comparison to placebo treated.  This protocol will recruit subjects undergoing PDT or 
control subjects (not undergoing PDT) at Department of Dermatology at Boonshoft 
School of Medicine at Wright State University where the PI is Chair of Pharmacology & 
Toxicology, with joint appointment in the WSU Department of Dermatology.  These 
studies are temporarily funded by WSU Department of Pharmacology and Toxicology. 
 
Please note that this study will recruit both subjects who are planning to undergo PDT as 
a part of their management of their actinic keratosis and normal control subjects.  This 
study will compare the effects of celecoxib vs placebo on the immune effects and 
effectiveness of PDT.  This study also assesses if celecoxib alone modulates immune 
responses in control subjects.  Thus, there will be 4 groups:  PDT + Celecoxib, PDT + 
placebo, Control + Celecoxib and Control + placebo. We plan to randomize the subjects 
and one of the study personnel (coordinators who will not have any contact with subjects 
except for making up the medicines will be unblinded).  These studies take advantage of 
the large numbers of patients undergoing PDT at WSU.   
These studies include: 
• 
Research subjects (those who receive PDT therapy) 
o Skin testing with intradermal Candida and Trichophyton antigens 
on two separate occasions. 
o Reporting a pain scale of 0-10 
o Urine collection (7 samples) 
o laboratory serum collection (2 venipunctures) 
o PDT-conducted for clinical reasons 
o 7 days of Celecoxib 200mg 2x per day or placebo 
o Follow up visits months 6 and 12 to assess actinic keratosis in 
treated areas. 
 
• 
Control subjects 


Version 4.0 21Apr2021 
 
3 
 
o Skin testing with intradermal Candida and Trichophyton antigens 
on two separate occasions. 
o Urine collection (7 samples) 
o Laboratory serum collection (2 venipunctures) 
o 7 days of celecoxib 200mg 2 x per day or placebo. 
  
 
2.0 Rationale and Specific Aims  PART III 
 
This protocol is designed to address multiple questions that have arisen since we have 
discovered 
that 
1) 
PDT 
in 
mice 
generates 
PAF 
and 
related 
oxidized 
glycerophosphocholines (ox-GPCs); and that 2) PDT suppressed systemic immunity 
against the allergen DNFB (dinitrofluorobenzene) in wild-type but not PAF-R-knockout 
mice [3]; and 3) the literature indicates that PDT induces localized immunosuppression 
[4]; and 4) our ongoing studies that PDT of human subjects results in PAF agonists in 
their skin; and finally, 5) our ongoing studies that PDT of human subjects results in 
immunosuppression.  
 
To test immunosuppression in humans, we plan two strategies.  The first strategy will 
test skin testing against Candida and Trichophyton antigens, before and after PDT 
treatment. 
 
We can also measure immune responses by taking peripheral blood mononuclear cells 
(PBMCs) from blood of subjects before/after PDT and incubate them with candida and 
trichophyton  as well as other common antigens, to see if can measure an immune 
response (by measuring gamma-interferon by EIA).  We can also measure levels of 
immunosuppressive T cells (Tregulatory cells) in the blood as well as the Treg-
associated cytokine interleukin-10 (IL-10).  Previously, we have demonstrated that when 
PAF is made, increased Tregs and IL-10 can be found in the mice.    Again, our studies 
have demonstrated in mice that COX-2 inhibitors can block immunosuppression 
associated with PDT, and PAF agonists [2,3,4]. 
 
This study will also collect urine specimens from the PDT-treated subjects (before and 
after PDT) to test them for COX-2 metabolites and reactive-oxygen-associated markers 
(isoprostanes).  We will also test urines in control subjects treated with celecoxib vs 
placebo.    
 
We hypothesize that these studies will demonstrate the following: 
1.  PDT will result in immunosuppression (as measured by increased IL-10 in serum, 
and lymphocyte assays, as well as diminished candida/trichophyton skin testing). 
2.  PDT will result in increased COX metabolites and isoprostanes in urine. 
3. Short-term Celecoxib treatment at commonly used dosages following PDT will inhibit 
the PDT-induced immunosuppression in comparison to placebo treatment. 
4. Short-term Celecoxib treatment following PDT will block the increased COX 
metabolites in urine, but will have no effect on the isoprostanes. 
5.  Subjects undergoing PDT treated with celecoxib will exhibit decreased levels of 
erythema and decreased pain/tenderness in comparison to placebo control. 
6.  PDT will be more effective (as measured by less actinic keratosis in the PDT-treated 
areas at 6 and 12 mo following PDT) in those subjects who underwent Celecoxib 
treatment compared to placebo treatment. 
7.  Control (non-PDT) subjects will not experience any differences in immune responses 
in those treated with celecoxib versus placebo treatment.    


Version 4.0 21Apr2021 
 
4 
 
 
This proof of concept study is valuable as it may form the basis of future studies to test if 
cyclooxygenase inhibitors can block PDT-mediated systemic immunosuppression, and 
potentially improve the long-term outcomes of PDT.    
 
3.0 Inclusion/Exclusion Criteria 
 
Inclusion Criteria for control subjects 
• 
Adult age 45 or older 
• 
Caucasion (Fair skin, Fitzpatrick types I and II) 
• 
Ability to understand and consent to the instructions of the study 
• 
Have access to stable transportation 
 
Inclusion Criteria for study subjects 
• 
 WSU dermatologist has prescribed PDT for the treatment of actinic damage 
(Presence of precancerous actinic keratoses whose treatment necessitates PDT 
with the BLU-U).  
• 
Undergoing PDT on greater than 5% body surface area: face and scalp, face and 
dorsal surface of arms, face and chest, face and back, or dorsal surface of arms 
alone, chest alone, or back alone. 
• 
Caucasian (Fair skin, Fitzpatrick types I and II) 
• 
Adult-age 45 or older 
• 
Ability to understand the informed consent and comply with instructions and have 
stable transportation. 
 
 
Exclusion Criteria for all subjects 
• 
PDT on less than 5% body surface area (eg, forehead) 
• 
Present treatment with corticosteroids or Non-steroidal anti-inflammatory drugs 
(e.g., cyclooxygenase inhibitors) within past 2 months (except low-dose 81 mg 
aspirin). 
• 
On antioxidant supplements (e.g., vitamin C) for past 2 months 
• 
Tanning bed use within last 3 months 
• 
PDT treatments within last 3 months 
• 
Significant health issues that could affect your immune system (e.g., uncontrolled 
Diabetes Mellitus, Rheumatoid arthritis, skin rashes, psoriasis) that could 
interfere with testing 
• 
Pregnant or nursing  
• 
No immunosuppression, and on no immunosuppressive medications or NSAIDS 
within past 30 days (except low-dose [81 mg daily] aspirin). 
• 
No signficant underlying diseases that could potentially interfere with the immune 
assays or cardiac or renal or liver problems. 
• 
History of blood clot or hypercoagulable state or GI bleed/ulceration. 
 
 
All subjects will be asked the screening questions below as part of the 
inclusion/exclusion criteria: 
• 
Are you 45 years old or older? 
• 
Do you regularly use tanning beds? 


Version 4.0 21Apr2021 
 
5 
 
• 
Are you being treated for anything that requires UV-treatments? 
• 
Have you had any diseases that got worse when you went in the sun? 
• 
Are you using topical or oral anti-inflammatory doses of NSAIDS or steroid? 
• 
Have you ever had any abnormal reactions or allergies to NSAIDS? 
• 
Are you taking any medications that warn you to stay out of the sun? 
• 
Have you ever had a reaction to medications that were applied to your skin? 
• 
Do you have severe sugar diabetes, heart problems or liver problems or other 
health problems that affect your immune system? 
• 
Have you had significant sun exposure or sunburn within the last 2 weeks? 
Tanning bed exposure in the past 3 months? 
• 
Have you had PDT in past 3 months? 
• 
Have you ever had a blood clot or other bleeding issues? 
• 
Have you ever had a stomach ulcer or bleeding from GI tract? 
• 
Are you pregnant or nursing? 
 
4.0 
Enrollment 
 
Subjects who will be undergoing PDT for actinic keratoses and controls will be recruited 
from the Dermatology clinics at WSU. Control subjects may also be recruited from other 
sites or other practices. The potential subjects will be told by their physician about the 
study. They will be reminded that this study will in no way benefit them directly and that 
their participation is only voluntary, and if they choose not to participate it will not impact 
their care or the interest of their providers in their case.  In addition, advertising flyers 
placed in the Wright State Department of Dermatology clinics will be used to seek PDT 
subjects and control subjects.    The flyers will require subjects who are interested in 
participating in the study to contact the PI, or the research office.  The PI, or study team 
member, will meet with the potential subjects. The PI will determine enrollment status 
based on the inclusion and exclusion criteria.  Each subject will be given all of the 
procedures and risks in writing and a signed informed consent statement will be 
obtained from each subject prior to enrollment in the study. The subjects will also be 
informed of the need to avoid sun exposure or tanning bed use for 3 months prior to 
PDT or during the study.    
 
5.0 Study Procedures 
 
Outlines of testing for PDT-treated subjects.  Please note that the Controls (see 
picture on page 9) will undergo all procedures EXCEPT the PDT.  Controls also 
will not have actinic keratosis counted/mapped and will not be following up to 
have actinic keratosis mapped at 6 and 12 months. 
 


Version 4.0 21Apr2021 
 
6 
 
 
DAY -2.  Consent, Skin testing, Venipuncture  
• 
Informed consent.  Explanation of the study, listing of all the required dates to 
return to the clinic for the study, and a signed informed consent will be obtained 
• 
Intended PDT treatment site will be noted, photographed and recorded 
• 
Actinic keratosis mapping.  Numbers of AKs will be counted and mapped on a 
diagram to allow us a base recording for future comparisons 
• 
Venipuncture.  20ml of blood will be drawn by routine phlebotomy. 
• 
Intradermal skin testing application.  An area on inner (volar) arm where planned 
PDT will not be taking place will be photographed, and intradermal injections of 
0.1 ml standardized solutions of commercially available Candida and 
Trichophyton protein antigens, or saline will be intradermally injected into skin to 
form small wheals.  The area will be photographed. 
 
DAY 0.  Read skin testing results, Urine specimen, PDT, Start celecoxib or placebo 
• 
Intradermal skin testing reading.  The skin reactions to the Candida and 
Trichophyton antigens will be visualized, photographed, and the size of the 
reactions measured using calipers. 
• 
Urine specimens.  Urine Sample will be obtained, and 6 sterile pre-labelled urine 
cups will be provided to the subject for home urine collection along with an 
orange opaque biohazard bag to store the samples in the freezer until they are 
returned to the research site.  
• 
Photodynamic Therapy (PDT).  PDT is a standard treatment at the WSU 
Department of Dermatology clinics and approximately 75-80 procedures are 
performed annually.  PDT is being conducted for clinical reasons and will 
therefore be submitted to the patient/patient’s insurance as routine care. 
Patients sign a separate informed consent for the PDT therapy and the PDT 
will follow standard clinical guidelines. Control subjects will not undergo the PDT 
treatment. 
• 
Celecoxib.  The subjects in the study arms which receive Celecoxib will be 
provided #14 capsules of 200mg celecoxib or 14 placebo capsules and 
instructed to take 1 capsule in the morning and 1 capsule in the evening.  They 
will be instructed to start the medication the same day (2 doses) and take as 
prescribed for a total of seven days.  The subjects will be provided a 7 day pill 
dispenser with AM/PM components for their use.  Funds from the study budget 


Version 4.0 21Apr2021 
 
7 
 
will pay for the prescription so that there will not be a cost to the subjects.  The 
dose of celecoxib was similar to that used long-term in previously reported 
studies where subjects were treated with celecoxib 200mg BID for ~ 1 year.  This 
is a dose and time frame that based upon our murine studies, should inhibit PAF-
induced immunosuppression.  
 
DAY 1-5 Urine Home Collection  
At night (~8 h post-PDT) on the day of PDT treatment, and days 1-5 First 
morning urine samples will be obtained in the sterile cups provided to the subject, 
each placed in the biohazard bag and stored in the freezer.   The subject will 
bring the urine samples back to the research clinic at day 7 study visit.  Subjects 
will be asked to fill out a Urine Collection Record form. Also, they will rate the 
pain associated with the PDT treatment on the Skin Pain Visual Analogue Scale 
(VAS). The scale will be 0 (no skin pain) to 10 (severe skin pain). 
 
DAY 7. Return of urine samples, Repeat skin testing to control and PDT-treated 
sites, Venipuncture. 
• 
Urine samples returned to the research site from research subjects 
• 
Subjects will bring empty pill dispensers. 
• 
Intradermal skin testing application.  An area on opposite inner (volar) arm where 
PDT did not take place, as well as a PDT-treated site (extensor arms, scalp, etc) 
will be photographed, and intradermal injections of 0.1 ml standardized solutions 
of commercially available Candida or Trichophyton protein antigens, or saline will 
be intradermally injected into skin to form small wheals.  The areas will be 
photographed. 
• 
Reporting amount of pain.  The 0-10 pain scale will be used again to query the 
subject as to amount of discomfort in the PDT-treated sites.  
• 
Venipuncture.  20ml of blood will be drawn by routine phlebotomy. 
 
 
DAY 9.  Read skin testing results 
• 
Intradermal skin testing reading.  The skin reactions to the Candida and 
Trichophyton antigens will be visualized, photographed, and the size of the 
reactions measured using calipers. 
 
6 months and 12 months. 
The subjects who were treated with PDT will be seen when they return to the 
dermatology clinic for their routine follow up care. We will use a body map to record the 
current numbers and sites where they have the precancerous AK lesions.  Their current 
numbers and sites will be compared to the numbers and locations of their AKs pre-
treatment with PDT obtained at visit Day 0. This comparison will help to define 
effectiveness of the therapy.  This information will become part of their medical record. 
 
 
 
 
 
 
 
 


Version 4.0 21Apr2021 
 
8 
 
CONTROL SUBJECTS 
 
 
 
DAY 0.  Consent, Skin testing, Venipuncture, Urine specimen  
• 
Informed consent.  Explanation of the study, listing of all the required dates to 
return to the clinic for the study, and a signed informed consent will be obtained 
• 
Venipuncture.  20ml of blood will be drawn by routine phlebotomy. 
• 
Intradermal skin testing application.  An area on inner (volar) arm will be 
photographed, and intradermal injections of 0.1 ml standardized solutions of 
commercially available Candida or Trichophyton protein antigens, or saline will 
be intradermally injected into skin to form small wheals.  The area will be 
photographed. 
• 
Urine specimens.  Urine Sample will be obtained, and 6 sterile pre-labelled urine 
cups will be provided to the subject for home urine collection along with an 
orange opaque biohazard bag to store the samples in the freezer until they are 
returned to the research site.  
 
DAY 2.  Read skin testing results, Start celecoxib or placebo 
• 
Intradermal skin testing reading.  The skin reactions to the Candida and 
Trichophyton antigens will be visualized, photographed, and the size of the 
reactions measured using calipers. 
• 
Celecoxib.  The subjects in the study arms which receive Celecoxib will be 
provided #14 capsules of 200mg celecoxib or 14 placebo capsules and 
instructed to take 1 capsule in the morning and 1 capsule in the evening.  They 
will be instructed to start the medication the same day (2 doses) and take as 
prescribed for a total of seven days.  The subjects will be provided a 7 day pill 
dispenser with AM/PM components for their use.  Funds from the study budget 
will pay for the prescription so that there will not be a cost to the subjects.  The 
dose of celecoxib was similar to that used long-term in previously reported 
studies where subjects were treated with celecoxib 200mg BID for ~ 1 year.  This 
is a dose and time frame that based upon our murine studies, should inhibit PAF-
induced immunosuppression. 
 
DAY 9. Repeat skin testing, Venipuncture. 
• 
Subjects will bring empty pill dispensers. 


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9 
 
• 
Intradermal skin testing application.  An area on opposite inner (volar) arm where 
previous skin testing did not take place will be photographed, and intradermal 
injections of 0.1 ml standardized solutions of commercially available Candida or 
Trichophyton protein antigens, or saline will be intradermally injected into skin to 
form small wheals.  The areas will be photographed. 
• 
Venipuncture.  20ml of blood will be drawn by routine phlebotomy. 
 
DAY 11.  Read skin testing results 
• 
Intradermal skin testing reading.  The skin reactions to the Candida and 
Trichophyton antigens will be visualized, photographed, and the size of the 
reactions measured using calipers. 
 
Compensation.   
The subjects will be compensated for involvement in the study.  
Research subjects require more visits and procedures than control subjects.  
 
Breakdown for each event is as follows: 
 
Consent 
 
 
 
$20.00   
PDT ($20), Control ($20) 
Venipuncture  
 
 
$10.00   
PDT ($20), Control ($20) 
Urine collection 
 
 
$5.00    
PDT ($35), Control ($35) 
Skin testing APPLICATION  
$15.00   
PDT ($45), Control ($45) 
Skin testing READING 
 
$20.00   
PDT ($40), Control ($40) 
Bonus for completing study   
$65.00   
PDT ($65), Control ($65) 
Follow up visits at 6 and 12 months $25.00   
PDT ($50)  
 
Hence the research (PDT) subjects may receive up to $ 275.00 and the control subjects 
up to $225.00.  
 
There is no cost for parking at the Wright State Physician’s Building.  Compensation is 
based upon completed study procedures and overall study completion. Since completion 
of study procedures are critical to the study findings if a subject cannot come to their 
scheduled visit (and cannot be quickly rescheduled) they will be removed from the study.  
Another subject will be enrolled in their place. Our goal is to enroll 48 subjects who 
complete the study.  
 
6.0  Reporting of Adverse Events or Unanticipated Problems involving Risk to 
       Participants or Others 
  
 
 
Risks of the study are as follows: 
 
1. Photodynamic therapy.  The risks to PDT are explained to the patient at the time 
of therapy decision and obtaining the informed consent for that standard of care 
procedure. 
PLEASE 
NOTE 
THAT 
PDT 
TREATMENT 
IS 
ALREADY 
RECOMMENDED FOR THE TREATMENT OF THE SUBJECT.  THEY WILL BE 
SIGNING A SEPARATE INFORMED CONSENT FOR THE TREAMTENT AND 
THEY/THEIR INSURANCE AS APPROPRIATE WILL BE BILLED FOR THE 
TREATMENT.   
2. Photography - the risk of photography is the possible loss of confidentiality.  
Pictures will not be of recognizable body parts or markings. Photos will be 


Version 4.0 21Apr2021 
 
10 
 
labeled with the study number and a code that does not identify the subject.  
Photos will not include any identifying information. 
3. Urine samples/non-invasive skin measurement with calipers.  There are no risks 
to these. 
4. Intradermal skin testing.  These procedures are used in dermatology and allergy 
to define the ability of a host to respond to the allergen of interest.  The majority 
of individuals will test positive to Candida protein antigens, and approximately 
50% of individuals test positive for antigens from the common dermatophyte 
fungus Trichophyton (which causes skin infections like “athlete’s feet”).  The side 
effects are localized skin inflammation and rash and occasionally can be painful.  
Very rarely an individual can have a systemic reaction.  If we do note that the 
subject’s first skin testing results in exaggerated reactions, then the subject will 
not undergo further testing with this antigen. 
5. Celecoxib  Celecoxib is a commonly used NSAID, which is COX-2 specific.  It 
was designed to have anti-inflammatory effects but have minimal side effects 
such as gastric distress, etc.  There have been multiple studies examining the 
long-term effects of celecoxib 200mg BID.  In particular, there was a published 
multicenter trial that indicated that long-term celecoxib was effective for 
diminishing the incidence of non-melanoma skin cancers [7].  It should be noted 
that in these studies the incidence of side effects of the celecoxib was similar to 
placebo.  Long-term use of COX-2-selective inhibitors have been associated with 
increased cardiovascular events due to a pro-coagulant effect [6].  However, this 
is not associated with short-term use.  There is a slight risk of GI bleeding.  
These effects will be minimized as we will recruit subjects with no history of GI 
ulceration/bleeding/blood clots. 
6. There is also the potential risk of loss of confidentiality, but this will be minimized  
 
as photos of the PDT- and treated sites will not allow the person to be 
 
identified, and will not expose buttocks/genitals.   Samples   will be labeled with 
 
numeric numbers  --III-001, III-002, III-003 etc. and the   study number (XXXX). 
Example III-001-XXXX.  
 
Risks of exaggerated PDT-related sunburn will be minimalized as subjects will be 
queried about abnormal reactions to sun or artificial sources of light, as well as if they 
are taking any medicine which is potentially photosensitizing.   
 
Adverse Event and Serious Adverse Event Collection and Reporting 
Information related to any adverse event will be collected at every study visit. The NCI-
CTCAE (Common Terminology Criteria for Adverse Events) volume 4.03 published June 
14, 2010 will be utilized for definition, grading scale and ‘study relatedness’ criteria of the 
event. Dr. Travers will be responsible for determining whether an AE is expected or 
unexpected. An AE will be considered unexpected if the nature, severity, or frequency of 
the event is not consistent with the risk information previously described for the study 
intervention. 
 
An adverse event (AE) means any untoward medical occurrence in a subject associated 
with the use of an intervention that does not necessarily have a causal relationship with 
the intervention. It can be any unfavorable and unintended sign (including abnormal 
laboratory findings), symptom or disease temporally associated with the investigation, 
whether or not considered intervention-related. 
 


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An unanticipated problem can be any unexpected, related or possibly related to the 
intervention, and increases risk to participants or others more than was previously 
known. All three must be true to have an unexpected problem. Each unanticipated 
problem is assessed as to the impact on subject safety. 
 
A serious adverse event (SAE) is any AE that results in one of the following outcomes: 
• 
Death 
• 
Life threatening 
• 
Requires hospitalization or prolonged hospitalization 
• 
A congenital anomaly/birth defect 
• 
Persistent or significant disability/incapacity 
• 
Requires intervention to prevent permanent impairment or damage 
 
All reports will simultaneously be submitted to NIAMS, through KAI. This will include: 
• 
Safety reports and meeting deliberations, including findings of adverse events 
and any comments, minutes, or recommendations resulting from the review of 
these periodic reports or meetings. 
• 
Expedited reporting, including SAEs and unanticipated problems, along with the 
independent assessment of such events, as appropriate, should be reported in 
an expedited manner. 
Each AE will be accompanied with the severity grade. The grades are as follows: 
• 
Grade 1 Mild: asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
• 
Grade 2 Moderate: minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental Activities of Daily Living (ADL)*. 
• 
Grade 3 Hospitalization: hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care ADL**. 
• 
Grade 4 Life-threatening consequences: urgent intervention indicated. 
• 
Grade 5 Death 
 
*Activities of Daily Living (ADL) refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc. 
**Self-care ADL refers to bathing, dressing and undressing, feeding self, using the 
toilet, etc. 
 
Grade 1 Mild and Grade 2 Moderate represent AEs that will be recorded at the time of 
occurrence and reported to DSMB at the next semi-annual meeting. DSMB meeting 
documents will be forwarded to the local IRB, as well as to the NIAMS, through KAI. 
 
Grade 3 – Grade 5 are considered SAEs. Serious adverse events include death, are life 
threatening, requires hospitalization or prolonged hospitalization, a congenital 
anomaly/birth defect, results in persistent or significant disability/incapacity, or require 
intervention to prevent permanent impairment or damage. All SAEs will be reported to 
the local IRB, the DSMB, and to NIAMS through KAI within 48 hours. 
 
In addition to severity grade, each AE will have the relationship to the study intervention 
assessed by Dr. Travers. The degree of certainty about causality will be graded using 
the categories below. 
• 
Related – The AE is known to occur with the study intervention, there is a 
reasonable possibility that the study intervention caused the AE. 


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• 
Not Related – There is not a reasonable possibility that the administration of the 
study intervention caused the event. 
 
Data Monitoring Plan 
Dr. Travers will be the individual responsible for monitoring the safety environment of the 
participants.  He will establish a Data and Safety Monitoring Board (DSMB) to assist in 
the safety oversight of this trial. Dermatology chair and board-certified dermatologists, 
Julian Trevino, MD, and Max Rubin, MD, will also serve on the DSMB. Also, Dr. R. 
Michael Johnson, MD, FACS, a board-certified plastic surgeon will serve on the DSMB. 
The DSMB will review the results of this study on a semi-annual basis and provide the 
Institutional Review Board (IRB) with a copy of that review report. Dr. Travers is not part 
of the DSMB as he is the PI for the trial. 
 
In the event of adverse outcome (e.g., exaggerated skin reaction to skin testing antigen), 
this will be treated appropriately (with no physician cost from Dr Travers, though a 
pharmacy fee could be incurred if any prescription agents needed) and will be noted and 
reported to the DSMB for their review.  Moreover, if any SAE or unanticipated events 
occur, these will also be reported to NIAMS within 48 hours.  Non-serious AEs will be 
reported to the DSMB semi-annually versus immediately.     
 
Dr. Travers is an experienced (~20 years) board-certified dermatologist who would be 
experienced in dealing with any potential adverse events should one arise.  More 
importantly, Dr. Travers’  role as a PI is to monitor the following: 1) ensuring that only 
subjects who meet the eligibility criteria are enrolled; 2) the informed consent process 
will be conducted appropriately and all subjects consented before proceeding with any 
study procedures; 3) Data will be collected and analyzed as outlined in the protocol; 4) 
Privacy and confidentiality of the subjects will be maintained; 5) Documentation of 
dropouts; 6) Documentation and reporting of all adverse events.     
He will be assisted by study coordinator Elizabeth Cates, who will assist with non-
invasive components of the study.  Another study coordinator (Amy Williams) will be in 
charge of dispensing the celecoxib vs placebo and will serve as unblinded personnel.   
 
7.0 Study Withdrawal/Discontinuation 
 
Participants will be instructed that taking part in this study is voluntary and they may 
choose not to take part or may leave the study at any time.  Emphasis will be stressed to 
the participants that leaving the study will not result in any penalty or loss of benefits that 
they are entitled.  
 
8.0 Statistical Considerations 
 
Statistical support will be provided by Dr. Genxin Li from WSU who will be collaborating 
with the PI.  There are numerous outcomes in this study.  They include: 1) levels of 
isoprostanes and PGE2 in urine before/after PDT; 2) Skin immune reactions; 3) T cell 
reactions; 4) numbers of actinic keratosis in the PDT-treated areas at 6 and 12 months.  
Moreover, these will be compared to control subjects control sites/pre-PDT as well as 
treatment with celecoxib/no celecoxib.  Outcomes will be analyzed using McNemar’s 
Test comparing the PDT-treated vs non-PDT treated area and celecoxib vs no celecoxib 
exposure. Secondary outcomes will be analyzed similarly using McNemar’s tests for 
binary outcomes and paired t-tests for numeric outcomes.  Exact and/or non-parametric 
methods will be considered if standard test assumptions are not met.  


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The sample size of 12 per group for PDT + celecoxib, PDT placebo, control + celecoxib 
and control placebo. Use of 12 allows reasonable discrimination for pilot studies 
(Pharmaceut. Stat. 4:287-291, 2005 [7]).  Once we have obtained preliminary data from 
these subjects and controls, we will have Dr. Li perform power analysis to define if more 
subjects are needed, and submit a new/amended study if appropriate. 
 
9.0 Privacy/Confidentiality Issues 
 
There is also the potential risk of loss of confidentiality, but this will be minimized as 
photos of the will not allow the person to be identified, and will only expose a small areas 
of buttocks and will not show any breasts/genitals. All conversations and procedures will 
take place in Wright State Physician’s building in the dermatology clinic in a private 
examining room.  The data will be kept in the locked office of the PI.  Samples and 
pictures from subjects will be coded by numbers as outlined above.  Photos will not be of 
recognizable body parts or markings.   
 
10.0 
Quality Control 
 
Quality control (QC) procedures will be done on all regulatory documents, research 
subject records and original source documentation. Any missing data will be 
communicated to the PI and coordinators for resolution. 
 
Following written Standard Operating Procedures (SOPs), the Clinical Research 
Operations Manager will verify that the trial is conducted, documented, and reported in 
compliance with the protocol, International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), and applicable regulatory requirements. 
 
The investigational site will keep records of all original source data. If requested, the site 
will provide access to original source documents to applicable regulatory agencies. 
 
11.0 Follow-up and Record Retention 
 
The duration of the study is expected to be 4 years from the first enrolled subject, and 
the duration of record retention will be 10 years.  After this time, records will be archived.  
We do not plan to biobank any samples. 
 
12.0 
COVID-19 Safety Plan 
 
All subjects are phone screened for COVID-19 symptoms the day before their 
appointment. When they arrive for their appointment they are instructed to call the 
research office prior to entering the building. Subjects are permitted to enter the building 
once research staff are ready to bring them back to the patient area. Everyone is 
required to wear masks when entering the building and have their temperature taken. 
Masks are provided to subjects who do not have one. 
 
The research staff are required to wear masks and check for symptoms prior to reporting 
to work. 
 


Version 4.0 21Apr2021 
 
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Patient room and equipment are cleaned and disinfected according to health authority 
guidance. During the research visit, subjects and research staff need to maintain the 
appropriate social distancing requirement when procedures are not being performed. 
 
In regards to contact tracing, the research office keeps track of all appointments on a 
calendar to remember who has been in the office. These appointments have the 
subject’s contact information such as full names, phone numbers, email addresses and 
approximate appointment length. Should subjects need to contact the research office, a 
copy of the informed consent with the office’s contact information is listed on the first 
page. 
 
13.0 References 
 
1. Matthews YJ. Damian DL. Topical photodynamic therapy is immunosuppressive in 
humans. British Journal of Dermatology. 162(3):637-41, 2010. 
 
2.  Zhang Q. Yao Y. Konger RL. Sinn AL. Cai S. Pollok KE. Travers JB. UVB radiation-
mediated inhibition of contact hypersensitivity reactions is dependent on the platelet-
activating factor system. Journal of Investigative Dermatology. 128(7):1780-7, 2008. 
 
3.  Ferracini M. Sahu RP. Harrison KA. Waeiss RA. Murphy RC. Jancar S. Konger RL. 
Travers JB.  Topical photodynamic therapy induces systemic immunosuppression via 
generation of platelet-activating factor agonists.  Journal of Investigative 
Dermatology.135:321-23, 2015. 
 
4.  Ullrich SE. Photoimmunology. Mutation Research. 571:185-205, 2005. 
 
5.  Elmets CA, Viner JL, Pentland AP et al.,  Chemoprevention of nonmelanoma skin 
cancer with celecoxib:  a randomized, double-blind placebo-controlled trial.  Journal of 
the National Cancer Institute 102:1835-44, 2010.   
 
6.  Patrono, C.  Cardiovascular effects of cyclooxygenase inhibitors: a mechanistic and 
clinical perspective.  British Journal of Clinical Pharmacology 82:957-64, 2016. 
 
7.   Julious, SA.  Sample size of 12 per group rule of thumb for a pilot study.  
Pharmaceutical  Statistics. 4:287-291, 2005. 
 
14.0 Abbreviations. 
 
AE; Adverse Event 
ALA; aminolevulinic acid 
BSA; Body surface area 
DNCB; dinitrochlorobenzene 
EIA; enzyme-linked immunoabsorbant assay 
NSAIDs; non-steroidal anti-inflammatory drugs 
Ox-GPCs; oxidized glycerophosphocholines 
PDT; photodynamic therapy  
PAF; platelet-activating factor 
PGE2; prostaglandin E2 
QC; Quality control 


Version 4.0 21Apr2021 
 
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SAE; Serious Adverse Event 
WSP; Wright state physician’s building 
WSU; Wright state university