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Efficacy of Topical Calcipotriol-assisted AFL-PDT in Actinic Keratosis

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ClinicalTrials.gov Identifier: NCT02976727
Recruitment Status : Completed
First Posted : November 29, 2016
Last Update Posted : November 29, 2016
Sponsor:
Information provided by (Responsible Party):
Song Ki-Hoon, Dong-A University

Brief Summary:
Vitamin D(Vit D) is a pro-differentiation agent that enhances the accumulation of protoporphyrin IX (PpIX) after MAL(methyl-aminolevulinate) incubation in actinic keratosis and may have significant benefit for the treatment of actinic keratosis by ablative fractional laser-primed photodynamic therapy (AFL-PDT).

Condition or disease Intervention/treatment Phase
Actinic Dermatosis Drug: Topical Vitamin D (Calcipotriol) application Drug: Placebo cream application Drug: lidocaine/prilocaine (5%) application Device: 2940-nm Er:YAG AFL pretreatment Drug: MAL application Other: Measurements of the fluorescence intensity Device: irradiation with red light-emitting diode lamp Phase 1

Detailed Description:

Photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is effective in the treatment of actinic keratosis (AK). Many strategies have been studied to improve the production of protoporphyrin IX (PpIX), to improve efficacy of PDT. Pre-treatment of the skin with fractional laser resurfacing is a novel alternative technique to improve the efficacy of PDT for AK. The investigators' previous studies showed that ablative fractional laser primed PDT (AFL-PDT) offered higher efficacy than conventional MAL-PDT in the treatment of AK. But, reduced response rates are also observed in thicker skin lesions, which may be due to insufficient PpIX accumulation within the target tissue.

Cellular differentiation leads to increased synthesis of PpIX from MAL and consecutively, differentiation therapy enhances photosensitization effect. Topical calcipotriol is a well-known pro-differentiation hormone and was demonstrated to influence the effect of PDT on keratinocytes.

The aim of this study was to evaluate efficacy of topical vitamin D in AFL-PDT for AK treatment. Consequently, the investigator compared efficacy, recurrence rate, cosmetic outcome and safety between VitD - AFL-PDT and conventional AFL-PDT.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Topical Calcipotriol-assisted Ablative Fractional Laser Photodynamic Therapy for the Treatment of Actinic Keratosis: 12-month Follow-up Results of a Prospective, Randomised, Comparative Trial
Study Start Date : May 2014
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin D

Arm Intervention/treatment
Experimental: GroupA (Vit-D pretreated AFL-PDT group )
Group A was treated with topical VitD-assisted AFL-PDT
Drug: Topical Vitamin D (Calcipotriol) application
Calcipotriol ointment 50 mcg/g (Daivonex, Leo Pharma, Denmark) was applied twice for daily on treatment area for 15 consecutive days.

Drug: lidocaine/prilocaine (5%) application
For AFL pre-treatment, lidocaine/prilocaine (5%) cream (EMLA; Astra Pharmaceuticals, LP, Westborough, MA, USA) was applied to the treatment area under occlusion for 30 min

Device: 2940-nm Er:YAG AFL pretreatment
After the anaesthetic cream was removed, AFL therapy was performed using a 2940-nm Er:YAG AFL (Joule; Sciton Inc., Palo Alto, CA, USA) at 300-550 µm ablation depth, level 1 coagulation, 22% treatment density and a single pulse

Drug: MAL application
Immediately after AFL treatment, an approximately 1- mm-thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. Incubation time is 3 hours

Other: Measurements of the fluorescence intensity
After 3 hours of application with MAL, saline wash was performed and fluorescence imaging analysis was performed with ultraviolet examination light (model 31602,356 nm; Burton Medical Products Crop.) at 10 cm height above the base of each lesion. The red fluorescence (610 nm-700 nm) was separated and extracted by ImageJ program and then used to measure the amount of 633 nm fluorescence of protoporphyrin IX.

Device: irradiation with red light-emitting diode lamp
After incubation for 3 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface, and a total light dose of 37 J/cm-2. All patients wore protective goggles during illumination.

Active Comparator: GroupB (Conventional AFL PDT group )
Group B was treated with conventional AFL-PDT
Drug: Placebo cream application
placebo cream (indistinguishable from calcipotriol cream by visual and physical appearance and sense of smell) was applied twice for daily on treatment area for 15 consecutive days.

Drug: lidocaine/prilocaine (5%) application
For AFL pre-treatment, lidocaine/prilocaine (5%) cream (EMLA; Astra Pharmaceuticals, LP, Westborough, MA, USA) was applied to the treatment area under occlusion for 30 min

Device: 2940-nm Er:YAG AFL pretreatment
After the anaesthetic cream was removed, AFL therapy was performed using a 2940-nm Er:YAG AFL (Joule; Sciton Inc., Palo Alto, CA, USA) at 300-550 µm ablation depth, level 1 coagulation, 22% treatment density and a single pulse

Drug: MAL application
Immediately after AFL treatment, an approximately 1- mm-thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. Incubation time is 3 hours

Other: Measurements of the fluorescence intensity
After 3 hours of application with MAL, saline wash was performed and fluorescence imaging analysis was performed with ultraviolet examination light (model 31602,356 nm; Burton Medical Products Crop.) at 10 cm height above the base of each lesion. The red fluorescence (610 nm-700 nm) was separated and extracted by ImageJ program and then used to measure the amount of 633 nm fluorescence of protoporphyrin IX.

Device: irradiation with red light-emitting diode lamp
After incubation for 3 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface, and a total light dose of 37 J/cm-2. All patients wore protective goggles during illumination.




Primary Outcome Measures :
  1. Differences of short-term complete response rates between VitD-AFL-PDT and AFL-PDT [ Time Frame: Short-term complete response rates were evaluated at 3 months after treatment ]
    Lesion responses were classified as either a complete response (complete disappearance of the lesion) or a noncomplete response (incomplete disappearance)

  2. Differences of long-term complete response rates between VitD-AFL-PDT and AFL-PDT [ Time Frame: Long-term complete response rates were evaluated at 12 months ]
    In all cases of complete response, the patients were reviewed at 12 months to check for recurrence. Recurrence was assessed by inspection, dermoscopy, photography, palpation, and histologic findings. For the histopathologic evaluation of treatment response, at the 12-month follow-up visit, a 3-mm punch biopsy of the treated AK lesion was performed in all cases of clinically incomplete response.

  3. Difference of the recurrence rates between VitD-AFL-PDT and AFL-PDT [ Time Frame: Recurrence rates were evaluated respectively at 12 months after treatment. ]
    In all cases of complete response, the patients were reviewed at 12 months to check for recurrence. Recurrence was assessed by inspection, dermoscopy, photography, palpation, and histologic findings. For the histopathologic evaluation of treatment response, at the 12-month follow-up visit, a 3-mm punch biopsy of the treated AK lesion was performed in all cases of clinically incomplete response.


Secondary Outcome Measures :
  1. Differences of cosmetic outcomes between VitD-AFL-PDT and AFL-PDT [ Time Frame: The overall cosmetic outcome was assessed 12 months after treatment ]
    Cosmetic outcomes were graded as excellent (slight redness or pigmentation change), good (moderate redness or pigmentation change), fair (slight-to-moderate scarring, atrophy, or induration), or poor (extensive scarring, atrophy, or induration)

  2. Difference of adverse events (erythema, post-inflammatory hyperpigmentation, edema, itching, oozing, bleeding) rates between VitD-AFL-PDT and AFL-PDT [ Time Frame: Within 12 months after each treatment ]
    Adverse events reported by the patient were noted at each follow-up visit, including severity, duration and need for additional therapy. All events due to PDT were described as phototoxic reactions (i.e., erythema, post-inflammatory hyperpigmentation, oedema, itching, oozing, bleeding and so forth).


Other Outcome Measures:
  1. Differences of the fluorescence intensity between VitD-AFL-PDT and AFL-PDT [ Time Frame: After 3 hours of application with MAL, fluorescence intensity imaging was assessed 10 minutes before illumination. ]
    After 3 hours of application with MAL, Fluorescence imaging analysis was performed on treatment area with ultraviolet examination light (model 31602,356 nm; Burton Medical Products Crop.) at 10 cm height above the base of each lesion. The red fluorescence was separated and extracted by ImageJ program and then used to measure the amount of 633 nm fluorescence of protoporphyrin IX.



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Ages Eligible for Study:   65 Years to 85 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Korean patients aged ≥ 18 years who had biopsy-confirmed Actinic keratosis lesions

Exclusion Criteria:

  • calcium metabolic disorder patients
  • photosensitivity disorder patients
  • lactating or pregnant women
  • patients with porphyria or a known allergy to any of the constituents of the MAL cream and lidocaine
  • patients with systemic disease, history of malignant melanoma, tendency of melasma development or keloid formation, any AK treatment of the area in the previous 4 weeks, or any conditions associated with a risk of poor protocol compliance; and patients on immunosuppressive treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02976727


Locations
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Korea, Republic of
Dong-A University
Busan, Seo-gu, Korea, Republic of, 602-715, Korea, Republic of
Sponsors and Collaborators
Dong-A University
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Responsible Party: Song Ki-Hoon, Assistant professor and chairman, Department of dermatology Dong-A University, College of medicine, Dong-A University
ClinicalTrials.gov Identifier: NCT02976727    
Other Study ID Numbers: DAUderma-07
First Posted: November 29, 2016    Key Record Dates
Last Update Posted: November 29, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Song Ki-Hoon, Dong-A University:
Vitamin D
Calcipotriol
Ablative fractional laser
Actinic keratosis
Photodynamic therapy
Additional relevant MeSH terms:
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Keratosis, Actinic
Keratosis
Skin Diseases
Precancerous Conditions
Neoplasms
Vitamin D
Lidocaine
Prilocaine
Lidocaine, Prilocaine Drug Combination
Calcipotriene
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents
Dermatologic Agents
Anesthetics, Combined