Efficacy of Iontophoresis-assisted AFL-PDT in Actinic Keratosis

Phase 1

Completed

• Conditions: Actinic Keratosis
• Interventions: Drug: lidocaine/prilocaine (5%) application; Drug: MAL application; Device: Iontophoresis application; Device: irradiation with red light-emitting diode lamp

• Registration Number: NCT02670655
• Lead Sponsor: Dong-A University

Brief Summary

Iontophoresis is a transdermal drug-delivery technique that enhances the transport of ionic species across membranes and may have significant benefit for the treatment of actinic keratosis (AK) by ablative fractional laser-primed photodynamic therapy (AFL-PDT).

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. Our previous studies showed that ablative fractional laser-primed PDT (AFL-PDT) offered higher efficacy than conventional MAL-PDT in the treatment of many diseases, such as AK, actinic cheilitis, Bowen's disease and basal cell carcinoma.1-4 Iontophoresis can be another method to improve efficacy of PDT. Iontophoresis is a transdermal drug-delivery technique which uses a mild electric current to enhance the transport of ionic species across membranes. Iontophoresis has been widely used to enhance drug delivery. Mizutani K et al.5 reported 5 AK patients successfully treated with direct-current pulsed iontophoresis-assisted 5-aminolevulinic acid (ALA)-PDT. Boddé HE et al.6 studied iontophoretic transport of ALA quantitatively in vitro and demonstrated enhanced transport of ALA by iontophoresis.

Until now, appropriate incubation time for AFL-PDT has not been elucidated. In our previous study, we investigated the efficacy of AFL-PDT with a short incubation time.7 Although AFL-PDT with a short incubation time (2 h) showed enhanced efficacy than conventional MAL-PDT with the standard incubation time, standard AFL-PDT with 3-h incubation time showed significantly higher efficacy than AFL-PDT with a short incubation time.

The aim of our study was to evaluate efficacy of iontophoresis in AFL-PDT for AK treatment. Consequently, we compared efficacy, recurrence rate, cosmetic outcome and safety between iontophoresis-assisted AFL-PDT with 2-h incubation time and conventional AFL-PDT with 2-h and 3-h incubation times.

Study Timeline

• Study Start: 2014-06
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-01
• Study First Submitted: 2016-01-28
• Study First Submitted QC: 2016-01-28
• Last Update Submitted: 2016-01-28
• Study First Posted: 2016-02-02
• Last Update Posted: 2016-02-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

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

Exclusion Criteria

• 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
• metal-containing device (cardiac pacemaker, orthopaedic implants, gynaecological devices)
• cardiac arrhythmia
• large skin erosion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Group A (short-time iontophoresis group)	lidocaine/prilocaine (5%) application	Group A was treated with iontophoresis-assisted AFL-PDT with a short incubation time (2 h)
Group A (short-time iontophoresis group)	Iontophoresis application	Group A was treated with iontophoresis-assisted AFL-PDT with a short incubation time (2 h)
Group C (long-time conventional group)	MAL application	Group C was treated with conventional AFL-PDT with a standard incubation time (3 h)
Group A (short-time iontophoresis group)	irradiation with red light-emitting diode lamp	Group A was treated with iontophoresis-assisted AFL-PDT with a short incubation time (2 h)
Group B (short-time conventional group)	MAL application	Group B was treated with conventional AFL-PDT with a short incubation time (2 h)
Group B (short-time conventional group)	lidocaine/prilocaine (5%) application	Group B was treated with conventional AFL-PDT with a short incubation time (2 h)
Group C (long-time conventional group)	lidocaine/prilocaine (5%) application	Group C was treated with conventional AFL-PDT with a standard incubation time (3 h)
Group A (short-time iontophoresis group)	MAL application	Group A was treated with iontophoresis-assisted AFL-PDT with a short incubation time (2 h)
Group B (short-time conventional group)	irradiation with red light-emitting diode lamp	Group B was treated with conventional AFL-PDT with a short incubation time (2 h)
Group C (long-time conventional group)	irradiation with red light-emitting diode lamp	Group C was treated with conventional AFL-PDT with a standard incubation time (3 h)

Primary Outcome Measures

Name	Time	Method
Differences of long-term complete response rates between three groups	Long-term complete response rates were evaluated at 12 months	The lesions were classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)
Differences of short-term complete response rates between three groups	Short-term complete response rates were evaluated at 3 months	The lesions were classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)
Differences of recurrence rates between three groups	Recurrence rates were evaluated at 12 months	In addition, the recurrence rate was evaluated 12 months after treatment. 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

Name	Time	Method
Differences of cosmetic outcomes between three groups	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)