Actinic Keratosis, Photodynamic Therapy
Conditions
Keywords
Actinic Keratosis, Photodynamic Therapy
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.
Interventions
DRUGCelecoxib 200mg
14 Celecoxib 200mg taken 1 in the morning and 1 in the evening.
DRUGPlacebo
14 placebo capsules taken 1 in the morning and 1 in the evening.
Sponsors
Wright State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for Control Subjects: * Adult age 45 or older * Caucasian (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: * Wright State University 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 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 the 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 significant 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Photodynamic Therapy (PDT)-Induced Systemic Immunosuppression From Baseline With Celecoxib Treatment. | Baseline and Day 7 | Investigator measures areas of inflammation from the reactions to intradermal (candida and trichophyton antigens) skin testing to calculate the areas of reaction. The areas of induration were measured using calipers with cm2 as the unit of measurement. The outcome measurement was calculated by using the cm2 measurements from baseline and Day 7 to calculate the percentage of initial reaction area. |
| Change From Baseline in the Number of Actinic Keratosis at 6 Months. | 6 Months after PDT treatment at Day 0 | Investigator will assess the number of actinic keratosis in the PDT-treated areas. |
| Change From Baseline in the Number of Actinic Keratosis at 12 Months. | 12 Months after PDT treatment at Day 0 | Investigator will assess the number of actinic keratosis in the PDT-treated areas. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Dayton, OH area. Patients who were prescribed to undergo photodynamic therapy (PDT) for actinic keratoses at Wright State Physicians were recruited. The control (patients who did not need photodynamic therapy) subjects where also recruited from Wright State Physicians or from the community.
Participants by arm
| Arm | Count |
|---|---|
| PDT + Celecoxib Patient receiving PDT taking 200mg celecoxib.
Celecoxib 200mg: 14 Celecoxib 200mg taken total over 7 days (1 is taken in the morning and 1 is taken in the evening). | 3 |
| PDT + Placebo Patient receiving PDT taking placebo.
Placebo: 14 placebo capsules taken total over 7 days (1 is taken in the morning and 1 is taken in the evening). | 3 |
| Control + Celecoxib Control subject not receiving PDT taking 200mg celecoxib.
Celecoxib 200mg: 14 Celecoxib 200mg taken total over 7 days (1 is taken in the morning and 1 is taken in the evening). | 3 |
| Control + Placebo Control subject not receiving PDT taking placebo.
Placebo: 14 placebo capsules taken total over 7 days (1 is taken in the morning and 1 is taken in the evening). | 3 |
| Total | 12 |
Baseline characteristics
| Characteristic | PDT + Celecoxib | PDT + Placebo | Control + Celecoxib | Control + Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Change From Baseline in the Number of Actinic Keratosis at 12 Months.
Investigator will assess the number of actinic keratosis in the PDT-treated areas.
Time frame: 12 Months after PDT treatment at Day 0
Population: Study was terminated before this outcome measurement time frame occurred, therefore data was not collected for this outcome.
Primary
Change From Baseline in the Number of Actinic Keratosis at 6 Months.
Investigator will assess the number of actinic keratosis in the PDT-treated areas.
Time frame: 6 Months after PDT treatment at Day 0
Population: Study was terminated before this outcome measurement time frame occurred, therefore data was not collected for this outcome.
p-value: >0.05t-test, 2 sided
Primary
Changes in Photodynamic Therapy (PDT)-Induced Systemic Immunosuppression From Baseline With Celecoxib Treatment.
Investigator measures areas of inflammation from the reactions to intradermal (candida and trichophyton antigens) skin testing to calculate the areas of reaction. The areas of induration were measured using calipers with cm2 as the unit of measurement. The outcome measurement was calculated by using the cm2 measurements from baseline and Day 7 to calculate the percentage of initial reaction area.
Time frame: Baseline and Day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PDT + Celecoxib | Changes in Photodynamic Therapy (PDT)-Induced Systemic Immunosuppression From Baseline With Celecoxib Treatment. | 152 Percentage of initial reaction area | Standard Error 107 |
| PDT + Placebo | Changes in Photodynamic Therapy (PDT)-Induced Systemic Immunosuppression From Baseline With Celecoxib Treatment. | 78 Percentage of initial reaction area | Standard Error 19 |
| Control + Celecoxib | Changes in Photodynamic Therapy (PDT)-Induced Systemic Immunosuppression From Baseline With Celecoxib Treatment. | 206 Percentage of initial reaction area | Standard Error 58 |
| Control + Placebo | Changes in Photodynamic Therapy (PDT)-Induced Systemic Immunosuppression From Baseline With Celecoxib Treatment. | 170 Percentage of initial reaction area | Standard Error 44 |
p-value: 0.53ANOVA
p-value: 0.727ANOVA