Efficacy of Iontophoresis-assisted AFL-PDT in Actinic Keratosis

NCT ID: NCT02670655

Last Updated: 2016-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2015-12-31

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.

Conditions

Actinic Keratosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group A (short-time iontophoresis group)

Group A was treated with iontophoresis-assisted AFL-PDT with a short incubation time (2 h)

Group Type: EXPERIMENTAL

lidocaine/prilocaine (5%) application

Intervention Type: 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

2940-nm Er:YAG AFL pretreatment

Intervention Type: 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

MAL application

Intervention Type: 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.

Iontophoresis application

Intervention Type: DEVICE

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

Intervention Type: DEVICE

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.

Group B (short-time conventional group)

Group B was treated with conventional AFL-PDT with a short incubation time (2 h)

Group Type: ACTIVE_COMPARATOR

lidocaine/prilocaine (5%) application

Intervention Type: 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

2940-nm Er:YAG AFL pretreatment

Intervention Type: 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

MAL application

Intervention Type: 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.

irradiation with red light-emitting diode lamp

Intervention Type: DEVICE

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.

Group C (long-time conventional group)

Group C was treated with conventional AFL-PDT with a standard incubation time (3 h)

Group Type: ACTIVE_COMPARATOR

lidocaine/prilocaine (5%) application

Intervention Type: 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

2940-nm Er:YAG AFL pretreatment

Intervention Type: 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

MAL application

Intervention Type: 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.

irradiation with red light-emitting diode lamp

Intervention Type: DEVICE

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.

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DEVICE

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.

Intervention Type: DRUG

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.

Intervention Type: DEVICE

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.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 84 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dong-A University

OTHER

Sponsor Role: lead

Responsible Party

Song Ki-Hoon

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

DAUderma-06

Identifier Type: -

Identifier Source: org_study_id