Efficacy of Iontophoresis-assisted AFL-PDT in Actinic Keratosis

Actinic Keratosis Clinical Trial

Official title:

Efficacy of Iontophoresis-assisted Ablative Fractional Laser Photodynamic Therapy With Short Incubation Time for the Treatment of Actinic Keratosis: 12-month Follow-up Results of a Prospective, Randomised, Comparative Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02670655
• Other study ID #: DAUderma-06
• Status: Completed
• Phase: Phase 1
• First received: January 28, 2016
• Last updated: January 28, 2016
• Start date: June 2014
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Dong-A University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 65 Years to 84 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Actinic Keratosis
• Keratosis
• Keratosis, Actinic

Intervention

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.

Device:
• Iontophoresis application
In Group A, ionotophoresis was performed on MAL-applied sites. We used iontophoresis (vitaliont II®, ITC Inc, Korea) with a patch. The active electrode was the anode, and 0.50-mA/cm2 current was applied to each AK lesion for 10 min.
• irradiation with red light-emitting diode lamp
After incubation for 2 (Group A and B) or 3 hours (Group C), 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Dong-A University

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Difference of adverse events (erythema, post-inflammatory hyperpigmentation, edema, itching, oozing, bleeding) rates between groups	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).	Within 12 months after each treatment	No
Primary	Differences of short-term complete response rates between three groups	The lesions were classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)	Short-term complete response rates were evaluated at 3 months	No
Primary	Differences of long-term complete response rates between three groups	The lesions were classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)	Long-term complete response rates were evaluated at 12 months	No
Primary	Differences of recurrence rates between three groups	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.	Recurrence rates were evaluated at 12 months	No
Secondary	Differences of cosmetic outcomes between three groups	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)	The overall cosmetic outcome was assessed 12 months after treatment	No