A Phase 1 interventional study of Aminolevulinic Acid Topical 20% Topical Solution and BLU-U blue light phototherapy illuminator in Actinic Keratoses, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-03-09.
Sponsored by University of California, San Francisco · Phase 1, Interventional, and Treatment
This is a randomized, single-blind controlled trial with parallel group design to determine whether daylight photodynamic therapy (PDT) affords a reduction in treatment symptoms of pain, burning, and pruritus as measured by 1) symptom level during the treatment period and 2) pain at the end of treatment exposure.
Actinic keratoses (AK) are common precancerous skin lesions that arise on sun-damaged skin. Treatment is aimed at preventing progression to cutaneous squamous cell carcinoma (SCC). First-line therapy for clinically apparent lesions includes cryotherapy and curettage; and field therapy options are topical 5-fluorouracil, imiquimod, ingenol mebutate, and photodynamic therapy (PDT). PDT involves the topical application of aminolevulinic acid (ALA), or one of its derivatives, as a photosensitizing agent. In response, rapidly proliferating, dysplastic cells preferentially accumulate protoporphyrin IX (PpIX). When PpIX is activated by blue or red light, singlet oxygen species are produced, resulting in cell death. PDT is beneficial due to its brief treatment course and efficacy in clearing AK. However, its main drawbacks are the adverse effects of pain, burning, pruritus, erythema, crusting, and inflammation associated with treatment. While conventional PDT uses red or blue artificial light to activate a high concentration of accumulated protoporphyrins, daylight PDT uses natural daylight to activate lower levels of protoporphyrins in a continuous manner. Daylight PDT, when compared with conventional PDT, has been associated with significantly less pain while achieving comparable efficacy for the treatment of AK. Daylight PDT is also more cost-effective and reduces the amount of time spent in clinic. Previous randomized studies comparing daylight PDT with conventional PDT have largely used methyl-aminolevulinate as the photosensitizer, have been intra-individual comparative studies, and have been performed in Nordic countries. Because the effective light dose from natural daylight depends on geographic location and seasonal and weather changes, randomized trials in different geographic and environmental conditions are of interest. The proposed randomized clinical trial investigates the tolerability and efficacy of daylight ALA-PDT for the treatment of AK in San Francisco for the first time; subjects will be randomized to various treatment arms, as opposed to previous split-face and intra-individual studies.
Exclusion Criteria:
This is considered the standard of care arm for photodynamic therapy for the treatment of actinic keratosis. This treatment arm includes: Acetone preparation, ALA topical application, 1 hour incubation, 16 minutes 40 seconds (16:40) BLU-U exposure, application of sunscreen. Drug intervention: Aminolevulinic acid HCl (ALA) topical solution 20% Device: BLU-U blue light phototherapy illuminator
Drug: Aminolevulinic Acid Topical 20% Topical Solution · Device: BLU-U blue light phototherapy illuminator
This treatment arm combines standard of care BLU-U exposure and daylight exposure. This treatment arm includes: Acetone preparation, ALA topical application, 15 minute incubation, 16:40 BLU-U exposure, application of sunscreen, 45 minute daylight exposure. Drug intervention: Aminolevulinic acid HCl (ALA) topical solution 20% Device: BLU-U blue light phototherapy illuminator
Drug: Aminolevulinic Acid Topical 20% Topical Solution · Device: BLU-U blue light phototherapy illuminator
This is the experimental arm. This treatment arm includes: Acetone preparation, ALA topical application, 15 minute incubation, application of sunscreen, 1 hour daylight exposure. Drug intervention: Aminolevulinic acid HCl (ALA) topical solution 20% Device: none
Drug: Aminolevulinic Acid Topical 20% Topical Solution
PDT involves the topical application of aminolevulinic acid (ALA), or one of its derivatives, as a photosensitizing agent. Subjects will receive ALA in all treatment arms (A, B, and C).
Depending on the treatment arm, subjects will either receive BLU-U exposure or not. Treatment arms A and B have BLU-U exposure and treatment arm C does not.
Change in Treatment Symptoms
Primary objective is to determine whether daylight PDT changes treatment symptoms of pain, stinging/burning, and itching/pruritus. This was measured using a visual analog scale from 0-10, with higher scores indicating worse treatment symptoms, or more pain/burning/itching. Lower scores indicate less pain, burning/stinging, and itching/pruritus. Positive numbers represent increases in symptoms and negative numbers represent decreases.
Time frame: 12 weeks
Percent Change in AK Lesion Count
The number of actinic keratoses within the treatment area was counted both pre and post-treatment. Then, the mean percent change from baseline actinic keratosis lesion count was calculated for each treatment group.
Time frame: 12 weeks
Reduction of AK Counts
The number of AK lesions within the treatment area was assessed both pre and post-treatment. Then, the number of participants with various levels of AK lesion reduction (100% reduction or greater than 75% reduction) was calculated for each treatment group. This outcome measures the proportion of subjects with complete (100%) and partial (greater than or equal to 75%) reduction of baseline actinic keratosis lesion counts at 12 weeks (study end).
Time frame: 12 weeks
Change in Local Skin Reaction From Pre-treatment to 12 Weeks Post-treatment
To determine whether daylight PDT affords a reduction in local skin reaction to treatment. A Local Skin Response Assessment scale will be used to measure this outcome. The investigators will grade categories including Erythema, Flaking/Scaling, crusting, swelling, Pustulation (pustules), and Erosion, on a 0-4 scale (total maximum score of 24). A higher score indicates more erythema, flaking, crusting, etc. and therefore a more robust skin reaction. A score of 0 represents no erythema, flaking, crusting, etc.
Time frame: 12 weeks
Peak Pain Score at Day 8 Post-treatment
Pain was measured by patient report with a visual analog scale from 0-10. 0 indicates no pain and 10 indicates the maximum pain score.
Time frame: 8 days post-treatment
| Milestone | A. Conventional Arm | B. Combination Arm | C. Daylight Arm |
|---|---|---|---|
| Started | 8 | 8 | 8 |
| Completed | 8 | 8 | 7 |
| Not completed | 0 | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 |
Primary objective is to determine whether daylight PDT changes treatment symptoms of pain, stinging/burning, and itching/pruritus. This was measured using a visual analog scale from 0-10, with higher scores indicating worse treatment symptoms, or more pain/burning/itching. Lower scores indicate less pain, burning/stinging, and itching/pruritus. Positive numbers represent increases in symptoms and negative numbers represent decreases.
| score on a scale | A. Conventional Arm | B. Combination Arm | C. Daylight Arm |
|---|---|---|---|
| Change in Treatment Symptoms | 3.9 (3.11 to 4.63) | 0.5 (-0.26 to 1.26) | 0.37 (-0.38 to 1.13) |
The number of actinic keratoses within the treatment area was counted both pre and post-treatment. Then, the mean percent change from baseline actinic keratosis lesion count was calculated for each treatment group.
| percent change | A. Conventional Arm | B. Combination Arm | C. Daylight Arm |
|---|---|---|---|
| Percent Change in AK Lesion Count | 63.9 ± 24.9 | 66.4 ± 29.5 | 61.8 ± 59.9 |
The number of AK lesions within the treatment area was assessed both pre and post-treatment. Then, the number of participants with various levels of AK lesion reduction (100% reduction or greater than 75% reduction) was calculated for each treatment group. This outcome measures the proportion of subjects with complete (100%) and partial (greater than or equal to 75%) reduction of baseline actinic keratosis lesion counts at 12 weeks (study end).
| Participants | A. Conventional Arm | B. Combination Arm | C. Daylight Arm |
|---|---|---|---|
| Partial Clearance | 2 | 3 | 5 |
| Complete Clearance | 2 | 2 | 2 |
To determine whether daylight PDT affords a reduction in local skin reaction to treatment. A Local Skin Response Assessment scale will be used to measure this outcome. The investigators will grade categories including Erythema, Flaking/Scaling, crusting, swelling, Pustulation (pustules), and Erosion, on a 0-4 scale (total maximum score of 24). A higher score indicates more erythema, flaking, crusting, etc. and therefore a more robust skin reaction. A score of 0 represents no erythema, flaking, crusting, etc.
| score on a scale | A. Conventional Arm | B. Combination Arm | C. Daylight Arm |
|---|---|---|---|
| Change in Local Skin Reaction From Pre-treatment to 12 Weeks Post-treatment | 1.0 (0.12 to 1.88) | 1.25 (0.37 to 2.13) | 1.0 (0.07 to 1.93) |
Pain was measured by patient report with a visual analog scale from 0-10. 0 indicates no pain and 10 indicates the maximum pain score.
| score on a scale | A. Conventional Arm | B. Combination Arm | C. Daylight Arm |
|---|---|---|---|
| Peak Pain Score at Day 8 Post-treatment | 3.5 (2.62 to 4.38) | 5.13 (4.25 to 6.00) | 4.00 (3.07 to 4.93) |
Collected over Adverse event data were collected from enrollment of first participant in Decomber 2017 through completion of final participant in September 2018. Adverse events were monitored for each patient from treatment up until 84 days following treatment.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| A. Conventional Arm | 0/8 (0%) | 0/8 (0%) | 8/8 (100%) |
| B. Combination Arm | 0/8 (0%) | 0/8 (0%) | 8/8 (100%) |
| C. Daylight Arm | 0/8 (0%) | 0/8 (0%) | 8/8 (100%) |
| Event | A. Conventional Arm | B. Combination Arm | C. Daylight Arm |
|---|---|---|---|
| Pruritus in Treatment AreaSkin and subcutaneous tissue disorders | 2/8 | 5/8 | 3/8 |
| Burning/Pain in Treatment AreaSkin and subcutaneous tissue disorders | 5/8 | 1/8 | 3/8 |
| ScalingSkin and subcutaneous tissue disorders | 3/8 | 0/8 | 3/8 |
| Erythema in Treatment AreaSkin and subcutaneous tissue disorders | 2/8 | 2/8 | 2/8 |
| Age, Categorical(Participants) | A. Conventional Arm | B. Combination Arm | C. Daylight Arm | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 1 | 1 | 1 | 3 |
| >=65 years | 7 | 7 | 7 | 21 |
| Age, Continuous(years) | A. Conventional Arm | B. Combination Arm | C. Daylight Arm | Total |
|---|---|---|---|---|
| Mean | 71.9 (64.4 to 85.1) | 77.7 (64.5 to 89.6) | 75.0 (60.7 to 93.9) | 75 (60 to 94) |
| Sex: Female, Male(Participants) | A. Conventional Arm | B. Combination Arm | C. Daylight Arm | Total |
|---|---|---|---|---|
| Female | 0 | 0 | 0 | 0 |
| Male | 8 | 8 | 8 | 24 |
| Ethnicity (NIH/OMB)(Participants) | A. Conventional Arm | B. Combination Arm | C. Daylight Arm | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 0 | 1 |
| Not Hispanic or Latino | 8 | 7 | 8 | 23 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | A. Conventional Arm | B. Combination Arm | C. Daylight Arm | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 |
| White | 8 | 8 | 8 | 24 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | A. Conventional Arm | B. Combination Arm | C. Daylight Arm | Total |
|---|---|---|---|---|
| United States | 8 | 8 | 8 | 24 |
| Treatment Area(Participants) | A. Conventional Arm | B. Combination Arm | C. Daylight Arm | Total |
|---|---|---|---|---|
| Face | 5 | 6 | 6 | 17 |
| Scalp | 3 | 2 | 2 | 7 |
| Actinic Keratosis Count(lesion count) | A. Conventional Arm | B. Combination Arm | C. Daylight Arm | Total |
|---|---|---|---|---|
| Mean | 12.1 ± 4.2 | 11.3 ± 3.0 | 10.3 ± 3.7 | 10.8 ± 4.9 |
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University of California, San Francisco