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

NCT02976727 | Completed Phase 1

• 1 other identifier: DAUderma-07
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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).

Conditions

Actinic Dermatosis

Keywords

Vitamin D; Calcipotriol; Ablative fractional laser; Actinic keratosis; Photodynamic therapy

Outcome Measures

Primary Outcomes (3)

• Differences of short-term complete response rates between VitD-AFL-PDT and AFL-PDT

  Lesion responses were classified as either a complete response (complete disappearance of the lesion) or a noncomplete response (incomplete disappearance)

  Short-term complete response rates were evaluated at 3 months after treatment

• Differences of long-term complete response rates between VitD-AFL-PDT and AFL-PDT

  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.

  Long-term complete response rates were evaluated at 12 months

• Difference of the recurrence rates between VitD-AFL-PDT and AFL-PDT

  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.

  Recurrence rates were evaluated respectively at 12 months after treatment.

Secondary Outcomes (2)

• Differences of cosmetic outcomes between VitD-AFL-PDT and AFL-PDT

  The overall cosmetic outcome was assessed 12 months after treatment

• Difference of adverse events (erythema, post-inflammatory hyperpigmentation, edema, itching, oozing, bleeding) rates between VitD-AFL-PDT and AFL-PDT

  Within 12 months after each treatment

Other Outcomes (1)

• Differences of the fluorescence intensity between VitD-AFL-PDT and AFL-PDT

  After 3 hours of application with MAL, fluorescence intensity imaging was assessed 10 minutes before illumination.

Study Arms (2)

GroupA (Vit-D pretreated AFL-PDT group )

EXPERIMENTAL

Group A was treated with topical VitD-assisted AFL-PDT

Drug: Topical Vitamin D (Calcipotriol) 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

GroupB (Conventional AFL PDT group )

ACTIVE COMPARATOR

Group B was treated with conventional AFL-PDT

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

Interventions

Topical Vitamin D (Calcipotriol) application DRUG

Calcipotriol ointment 50 mcg/g (Daivonex, Leo Pharma, Denmark) was applied twice for daily on treatment area for 15 consecutive days.

GroupA (Vit-D pretreated AFL-PDT group )

Placebo cream application DRUG

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.

GroupB (Conventional AFL PDT group )

lidocaine/prilocaine (5%) application DRUG

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

GroupA (Vit-D pretreated AFL-PDT group ); GroupB (Conventional AFL PDT group )

2940-nm Er:YAG AFL pretreatment DEVICE

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

GroupA (Vit-D pretreated AFL-PDT group ); GroupB (Conventional AFL PDT group )

MAL application DRUG

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

GroupA (Vit-D pretreated AFL-PDT group ); GroupB (Conventional AFL PDT group )

Measurements of the fluorescence intensity OTHER

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.

GroupA (Vit-D pretreated AFL-PDT group ); GroupB (Conventional AFL PDT group )

irradiation with red light-emitting diode lamp DEVICE

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.

GroupA (Vit-D pretreated AFL-PDT group ); GroupB (Conventional AFL PDT group )

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dong-A University: lead

Study Sites (1)

Dong-A University

Busan, Seo-gu, Korea, Republic Of, 602-715, South Korea

Location

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

Vitamin D; calcipotriene; Lidocaine; Prilocaine; Radiotherapy

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor and chairman, Department of dermatology Dong-A University, College of medicine

Study Record Dates

• First Submitted: November 5, 2016
• First Posted: November 29, 2016
• Study Start: May 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: November 29, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)