Daylight Photodynamic Therapy for Actinic Keratosis

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT03322293
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 3
• Actual Duration (Months): 19
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Actinic Keratoses	Drug: Aminolevulinic Acid Topical 20% Topical Solution; Device: BLU-U blue light phototherapy illuminator	Phase 1

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized (1:1:1), single-blind controlled trial with parallel group designRandomized (1:1:1), single-blind controlled trial with parallel group design
• Masking: Single (Investigator)
• Masking Description: This is a single-blinded study, as the subject cannot be blinded to treatment. Disease assessments and aminolevulinic acid (ALA) application will be performed by the blinded investigator. History, concomitant medications, randomization, light exposure, symptom assessment, and Skindex-16 will be administered by the unblinded study coordinator.
• Primary Purpose: Treatment
• Official Title: Tolerability and Efficacy of Daylight Aminolevulinic-acid-photodynamic Therapy (ALA-PDT) Compared With Conventional ALA-PDT for Treatment of Actinic Keratosis on the Face or Scalp
• Actual Study Start Date: Dec 1, 2017
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Jul 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A. Conventional arm 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; 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).; Device: BLU-U blue light phototherapy illuminator; 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.
Experimental: B. Combination arm 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; 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).; Device: BLU-U blue light phototherapy illuminator; 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.
Experimental: C. Daylight arm 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).

Outcome Measures

Primary Outcome Measures

1. Change in Treatment Symptoms [12 weeks]

   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.

Secondary Outcome Measures

1. Percent Change in AK Lesion Count [12 weeks]

   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.

2. Reduction of AK Counts [12 weeks]

   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).

3. Change in Local Skin Reaction From Pre-treatment to 12 Weeks Post-treatment [12 weeks]

   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.

4. Peak Pain Score at Day 8 Post-treatment [8 days 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults at least 18 years old.

• Subjects must be able to read, sign, and understand the informed consent

• Subjects have at least 4 and no more than 20 clinically typical, visible actinic keratoses in the target treatment area on the face or scalp.

• Subject must be willing to forego any other treatments for AK in the treatment area on the face or scalp, during the study period, and for 14 days prior to screening; including cryotherapy, topical 5-fluorouracil, imiquimod, and ingenol mebutate.

• Subjects who have previously received PDT must undergo at least an 8-week washout period prior to enrollment in study.

• Subject must be willing and able to participate in the study and to comply with all study requirements including concomitant medication and other treatment restrictions, and telephone interview.

• If subject is a female of childbearing potential she must have a negative urine pregnancy test result prior to study treatment initiation and must agree to use an approved method of birth control while enrolled in the study. Women who are pregnant, lactating, or planning to become pregnant during the study period are excluded from the study.

Exclusion Criteria:

• Subjects with any dermatologic disease in the treatment area that may be exacerbated by the treatment proposed or that might impair the evaluation of AKs.

• Subjects who are currently participating in another clinical study or have completed another clinical study with an investigational drug or device on the study area within 30 days prior to study treatment initiation.

• Subjects with any medical condition that, in the opinion of the investigator, makes the patient unsuitable for the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Dermatology	San Francisco	California	United States	94115

Sponsors and Collaborators

• University of California, San Francisco

Investigators

• Principal Investigator: Sarah Arron, MD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 13, 2017

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT03322293
• Other Study ID Numbers: Daylight PDT
• First Posted: Oct 26, 2017
• Last Update Posted: Mar 9, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by University of California, San Francisco: Actinic Keratoses; photodynamic therapy; aminolevulinic acid; precancerous skin lesion
• Additional relevant MeSH terms: Keratosis, Actinic; Keratosis; Aminolevulinic Acid

Study Results

Participant Flow

Arm/Group Title	A. Conventional Arm	B. Combination Arm	C. Daylight Arm
Arm/Group Description	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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).
Period Title: Overall Study
STARTED	8	8	8
COMPLETED	8	8	7
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	A. Conventional Arm	B. Combination Arm	C. Daylight Arm	Total
Arm/Group Description	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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).	Total of all reporting groups
Overall Participants	8	8	8	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 12.5%	1 12.5%	1 12.5%	3 12.5%
>=65 years	7 87.5%	7 87.5%	7 87.5%	21 87.5%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	71.9	77.7	75.0	75
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	8 100%	8 100%	8 100%	24 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 12.5%	0 0%	1 4.2%
Not Hispanic or Latino	8 100%	7 87.5%	8 100%	23 95.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	8 100%	8 100%	8 100%	24 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	8 100%	8 100%	24 100%
Treatment Area (Count of Participants)
Face	5 62.5%	6 75%	6 75%	17 70.8%
Scalp	3 37.5%	2 25%	2 25%	7 29.2%
Actinic Keratosis Count (lesion count) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lesion count]	12.1 (4.2)	11.3 (3.0)	10.3 (3.7)	10.8 (4.9)

Outcome Measures

1. Primary Outcome

Title	Change in Treatment Symptoms
Description	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

Outcome Measure Data

Analysis Population Description

24 participants enrolled in the study who underwent treatment were analyzed.

Arm/Group Title	A. Conventional Arm	B. Combination Arm	C. Daylight Arm
Arm/Group Description	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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).
Measure Participants	8	8	8
Mean (95% Confidence Interval) [score on a scale]	3.9	0.5	0.37

2. Secondary Outcome

Title	Percent Change in AK Lesion Count
Description	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

Outcome Measure Data

Analysis Population Description

24 participants who underwent treatment were analyzed, with the data for the 1 participant in group C who was lost-to-follow up carried forward. This means that data for 8 participants in each subgroup and 24 participants overall was analyzed for this outcome.

Arm/Group Title	A. Conventional Arm	B. Combination Arm	C. Daylight Arm
Arm/Group Description	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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).
Measure Participants	8	8	8
Mean (Standard Deviation) [percent change]	63.9 (24.9)	66.4 (29.5)	61.8 (59.9)

3. Secondary Outcome

Title	Reduction of AK Counts
Description	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

Outcome Measure Data

Analysis Population Description

24 participants who underwent treatment were analyzed, with data from the 1 participant in group C who was lost to follow up carried forward. 8 Participants were included in data analysis for each subgroup, with 24 participants included overall.

Arm/Group Title	A. Conventional Arm	B. Combination Arm	C. Daylight Arm
Arm/Group Description	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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).
Measure Participants	8	8	8
Partial Clearance	2 25%	3 37.5%	5 62.5%
Complete Clearance	2 25%	2 25%	2 25%

4. Secondary Outcome

Title	Change in Local Skin Reaction From Pre-treatment to 12 Weeks Post-treatment
Description	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

Outcome Measure Data

Analysis Population Description

24 participants who underwent treatment were analyzed, with data from the 1 participant lost to follow up in Group C carried forward. 8 participants were analyzed for each subgroup, with 24 participants analyzed overall.

Arm/Group Title	A. Conventional Arm	B. Combination Arm	C. Daylight Arm
Arm/Group Description	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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).
Measure Participants	8	8	8
Mean (95% Confidence Interval) [score on a scale]	1.0	1.25	1.0

5. Secondary Outcome

Title	Peak Pain Score at Day 8 Post-treatment
Description	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

Outcome Measure Data

Analysis Population Description

24 participants who underwent treatment were analyzed, with data from the 1 participant from Group C who was lost to follow up carried forward. 8 participants from each subgroup were analyzed, with 24 participants overall. Mean peak pain on day 8 with a 95% confidence interval for each treatment group on day 8 is reported below.

Arm/Group Title	A. Conventional Arm	B. Combination Arm	C. Daylight Arm
Arm/Group Description	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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). BLU-U blue light phototherapy illuminator: 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.	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 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).
Measure Participants	8	8	8
Mean (95% Confidence Interval) [score on a scale]	3.5	5.13	4.00

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	Adverse events were collected at study visits by asking the participants and eliciting any relevant patient-reported adverse event information. Adverse events were defined using Common Terminology Criteria version 5.0.
Arm/Group Title	A. Conventional Arm		B. Combination Arm		C. Daylight Arm
Arm/Group Description	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 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). BLU-U blue light phototherapy illuminator: 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.		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 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). BLU-U blue light phototherapy illuminator: 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.		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 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).
All Cause Mortality
	A. Conventional Arm		B. Combination Arm		C. Daylight Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)
Serious Adverse Events
	A. Conventional Arm		B. Combination Arm		C. Daylight Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	A. Conventional Arm		B. Combination Arm		C. Daylight Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		8/8 (100%)		8/8 (100%)
Skin and subcutaneous tissue disorders
Pruritus in Treatment Area	2/8 (25%)	2	5/8 (62.5%)	5	3/8 (37.5%)	3
Burning/Pain in Treatment Area	5/8 (62.5%)	5	1/8 (12.5%)	1	3/8 (37.5%)	3
Scaling	3/8 (37.5%)	3	0/8 (0%)	0	3/8 (37.5%)	3
Erythema in Treatment Area	2/8 (25%)	2	2/8 (25%)	2	2/8 (25%)	2

Limitations/Caveats

This was a small, 24 person pilot study performed at the San Francisco Veterans Affairs Medical Center. As such, the study was not powered to detect statistically significant differences in treatment efficacies.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.