Actinic Cheilitis
Conditions
Keywords
Actinic cheilitis, Photodynamic therapy, Levulan, Blue light
Brief summary
To evaluate the safety and efficacy of PDT with blue light and topical Levulan in the treatment of actinic cheilitis.
Detailed description
The study will consist of a screening visit, up to three scheduled treatments, and two scheduled office visits. There can be a three-day window period for each scheduled visit in order to accommodate the subject's schedule and unforeseen scheduling conflicts. 1. Visit 1 (Screening): Subjects can be screened for the study up to two weeks before Visit 2 (Baseline). During screening, the study will be reviewed, written informed consent obtained, and eligibility confirmed. If applicable, the washout from prohibited medications or treatments will be determined at this visit. 2. Visit 2 (Baseline): Following signed, written informed consent and confirmation of eligibility, all subjects will have their lips photographed. Medical history, dermatologic exam, urine pregnancy test (if applicable), review of concomitant medications, clinical evaluations, and tolerability assessments will be performed at this visit. Study medication application to clean skin will be followed by a 90 minute incubation period under occlusion. Subsequently, patients will be exposed to blue light therapy for 16 minutes and 40 seconds. Post-therapy assessments will be performed afterwards, as well as education on appropriate sun protection methods. 3. Visits 3-4: Subjects will return every six weeks for up to two additional treatments. Treatment will be discontinued once the patient has achieved clinical clearance. Tolerability assessments, study medication application, blue light therapy, post-therapy assessments, and photographs will be performed. 4. Visit 5-6 (End of Study): Subjects will return 12 and 24 weeks after the last treatment for clinical evaluations, tolerability assessments, and photographs.
Interventions
PROCEDUREPhotodynamic therapy with blue light
Sponsors
DUSA Pharmaceuticals, Inc.
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be able to understand and voluntarily sign an informed consent form * Must be male or female ≥ 18 years of age at the time of consent * Must be able to adhere to the study visit schedule and other protocol requirements * Must have a diagnosis of actinic cheilitis by histopathological evaluation of biopsy specimen or clinical presentation
Exclusion criteria
* Inability to provide voluntarily consent or mentally incompetent * Active herpes labialis lesions * Subjects with any condition which places the subject at unacceptable risk if he/she were to participate in the study, or confounds the ability to interpret data from the study * Subjects with any other skin condition that might affect the evaluation of the study disease * Pregnant or breastfeeding female subjects * Subjects who have used any investigational medication within one month prior to study entry * Subjects who have been previously exposed to PDT and/or topical Levulan therapy for the treatment of actinic cheilitis * Subjects who have used local therapy (e.g. cryotherapy) or topical treatment (e.g. 5% fluorouracil) within three months of study entry * Subjects who have used an oral photosensitizing drug (e.g. Declomycin) within six months of study entry * Subjects who are currently using photosensitizing agents (e.g. thiazides, tetracyclines, fluoroquinolones, phenothiazines, and sulfonamides) because of the risk of augmented photosensitivity * Subjects who are frequently exposed to ultraviolet radiation (e.g. lifeguards, construction workers, frequent sunbed users, etc.) * Subjects with a history of cutaneous photosensitization, porphyria, hypersensitivity to porphyrins, or photodermatosis * Subjects with a known hypersensitivity to Levulan * Subjects who are immunocompromised
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change in Clearance From Baseline | Visit 2 (Baseline) to Visit 5 or 6 (Week 24 or 36) | Clearance will be estimated clinically as minimal (0%-25%), mild (26%-50%), moderate (51%-75%), good (76%-99%), or complete (100%). Results will also be evaluated by comparing photographs before and immediately after treatments, and 12 and 24 weeks after the last treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change in Participant Reported Pain | Baseline to Week 36 | Subject reported pain before, during and after blue light illumination was documented using a Visual Analogue Scale (VAS) from 0 (no pain) to 10 (worst pain imaginable). The maximum change in pain is 10 for each occurrence (pain before compared to during treatment and pain during compared to after treatment). This is multiplied by the number of subjects and then divided by the number of treatments to generate the range. The summation of the change between subject reported pain prior to compared to during blue light treatment was divided by the total number of treatments to obtain the average value. The summation of the change between subject reported pain during compared to after blue light treatment was divided by the total number of treatments to obtain the average value. |
| Average Change in Local Skin Reactions to Blue Light Treatment | Baseline to Week 36 | Assessments of swelling, erythema, and flaking/scaling were conducted after each treatment and two days post-treatment using a five-point ordinal scale (0: none to 4: severe). The average change in swelling, erythema and flaking/scaling after each treatment and two days post treatment were divided by the 50 total treatments to obtain the average value. |
| The Number of Participants Who Developed a Local Skin Reaction to Blue Light Treatment: Vesiculation/Pustulation, Erosion/Ulceration, Crusting and Hyperpigmentation | Baseline to Week 36 | Assessments of vesiculation/pustulation, erosion/ulceration, and crusting were conducted immediately after each blue light treatment using a five-point ordinal scale (0: none to 4: severe). The presence or absence of hyperpigmentation in the treatment area was also documented after each treatment visit. The total number of participants who developed a local skin reaction is documented. |
| Number of Participants With Adverse Events | Baseline to Week 36 | Evaluation of any reported local or systemic events outside the treatment area and other than those specified under local skin reactions or PDT reactions. |
Countries
United States
Participant flow
Recruitment details
Twenty four patients were screened to participate. Three men and one woman did not meet criteria to participate in the study.
Pre-assignment details
Twenty four patients were screened to participate, but only 20 entered into the study (3 men and 1 woman screen failed). This was an open label proof of concept study and our goal was to enroll a total of 20 patients, which we achieved.
Participants by arm
| Arm | Count |
|---|---|
| Photodynamic Therapy With Blue Light Photodynamic therapy (PDT) with aminolevulinic acid hydrochloride (HCl) and blue light to the affected area of the lips every six weeks up to three treatments. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Photodynamic Therapy With Blue Light |
|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 19 |
| Income >$100,000 | 4 participants |
| Income $10,000-25,000 | 1 participants |
| Income $26,000-50,000 | 1 participants |
| Income $51,000-75,000 | 4 participants |
| Income $76,000-100,000 | 4 participants |
| Income Prefer not to answer | 6 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 3 / 20 |
| serious Total, serious adverse events | 1 / 20 |
Outcome results
Primary
Number of Participants With a Change in Clearance From Baseline
Clearance will be estimated clinically as minimal (0%-25%), mild (26%-50%), moderate (51%-75%), good (76%-99%), or complete (100%). Results will also be evaluated by comparing photographs before and immediately after treatments, and 12 and 24 weeks after the last treatment.
Time frame: Visit 2 (Baseline) to Visit 5 or 6 (Week 24 or 36)
Population: Twenty patients were enrolled into the study. Please see baseline characteristics to understand the patient demographic.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Photodynamic Therapy With Blue Light | Number of Participants With a Change in Clearance From Baseline | 0% improvement at V6 (week 36) | 1 Participants |
| Photodynamic Therapy With Blue Light | Number of Participants With a Change in Clearance From Baseline | 50% improvement at V6 (week 36) | 1 Participants |
| Photodynamic Therapy With Blue Light | Number of Participants With a Change in Clearance From Baseline | 75% improvement at V6 (week 36) | 9 Participants |
| Photodynamic Therapy With Blue Light | Number of Participants With a Change in Clearance From Baseline | 100% % improvement at V6 (week 36) | 4 Participants |
| Photodynamic Therapy With Blue Light | Number of Participants With a Change in Clearance From Baseline | Discontinued/Withdrew/Lost to follow up | 5 Participants |
Secondary
Average Change in Local Skin Reactions to Blue Light Treatment
Assessments of swelling, erythema, and flaking/scaling were conducted after each treatment and two days post-treatment using a five-point ordinal scale (0: none to 4: severe). The average change in swelling, erythema and flaking/scaling after each treatment and two days post treatment were divided by the 50 total treatments to obtain the average value.
Time frame: Baseline to Week 36
Population: Twenty participants completed 50 treatments and the change in local skin reaction (pre-treatment, during treatment and post-treatment) was evaluated at each visit.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Photodynamic Therapy With Blue Light | Average Change in Local Skin Reactions to Blue Light Treatment | Swelling | 0.72 units on a scale |
| Photodynamic Therapy With Blue Light | Average Change in Local Skin Reactions to Blue Light Treatment | Erythema | 0.58 units on a scale |
| Photodynamic Therapy With Blue Light | Average Change in Local Skin Reactions to Blue Light Treatment | Flaking/Scaling (Skin Dryness) | 1.82 units on a scale |
Secondary
Average Change in Participant Reported Pain
Subject reported pain before, during and after blue light illumination was documented using a Visual Analogue Scale (VAS) from 0 (no pain) to 10 (worst pain imaginable). The maximum change in pain is 10 for each occurrence (pain before compared to during treatment and pain during compared to after treatment). This is multiplied by the number of subjects and then divided by the number of treatments to generate the range. The summation of the change between subject reported pain prior to compared to during blue light treatment was divided by the total number of treatments to obtain the average value. The summation of the change between subject reported pain during compared to after blue light treatment was divided by the total number of treatments to obtain the average value.
Time frame: Baseline to Week 36
Population: Twenty participants completed 50 treatments and the change in local skin reaction (pre-treatment, during treatment and post-treatment) was evaluated at each visit.~Number of Patients by Number of Treatments received:~One Treatment: 4 Two Treatments :2 Three Treatments:14
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Photodynamic Therapy With Blue Light | Average Change in Participant Reported Pain | Avg change of pain prior to tx to during tx | 2.86 units on a scale |
| Photodynamic Therapy With Blue Light | Average Change in Participant Reported Pain | Avg change of pain during tx to after tx | -0.76 units on a scale |
Secondary
Number of Participants With Adverse Events
Evaluation of any reported local or systemic events outside the treatment area and other than those specified under local skin reactions or PDT reactions.
Time frame: Baseline to Week 36
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Photodynamic Therapy With Blue Light | Number of Participants With Adverse Events | Upper respiratory infection (URI) | 1 Participants |
| Photodynamic Therapy With Blue Light | Number of Participants With Adverse Events | Lesion on mid chest | 1 Participants |
| Photodynamic Therapy With Blue Light | Number of Participants With Adverse Events | Red spots | 1 Participants |
| Photodynamic Therapy With Blue Light | Number of Participants With Adverse Events | Bleeding esophageal ulcer | 1 Participants |
Secondary
The Number of Participants Who Developed a Local Skin Reaction to Blue Light Treatment: Vesiculation/Pustulation, Erosion/Ulceration, Crusting and Hyperpigmentation
Assessments of vesiculation/pustulation, erosion/ulceration, and crusting were conducted immediately after each blue light treatment using a five-point ordinal scale (0: none to 4: severe). The presence or absence of hyperpigmentation in the treatment area was also documented after each treatment visit. The total number of participants who developed a local skin reaction is documented.
Time frame: Baseline to Week 36
Population: Twenty participants completed 50 treatments and the change in local skin reaction (pre-treatment, during treatment and post-treatment) was evaluated at each visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Photodynamic Therapy With Blue Light | The Number of Participants Who Developed a Local Skin Reaction to Blue Light Treatment: Vesiculation/Pustulation, Erosion/Ulceration, Crusting and Hyperpigmentation | Hyperpigmentation | 1 participants |
| Photodynamic Therapy With Blue Light | The Number of Participants Who Developed a Local Skin Reaction to Blue Light Treatment: Vesiculation/Pustulation, Erosion/Ulceration, Crusting and Hyperpigmentation | Vesiculation/Pustulation | 2 participants |
| Photodynamic Therapy With Blue Light | The Number of Participants Who Developed a Local Skin Reaction to Blue Light Treatment: Vesiculation/Pustulation, Erosion/Ulceration, Crusting and Hyperpigmentation | Erosion/Ulceration | 0 participants |
| Photodynamic Therapy With Blue Light | The Number of Participants Who Developed a Local Skin Reaction to Blue Light Treatment: Vesiculation/Pustulation, Erosion/Ulceration, Crusting and Hyperpigmentation | Crusting | 4 participants |