Fractional Laser Assisted Delivery of Anesthetics

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the efficacy of fractional CO2 laser assisted delivery of topically applied anesthetics (articaine hydrochloride 40 mg/ml and epinephrine 10 μg/ml solution and EMLA cream) regarding to anesthesia of the skin.

Detailed Description
-----------------
Rationale: In dermatology, many minor surgical and laser procedures are carried out under local anesthesia of the skin. Anesthesia using topical formulations is time consuming, as the anesthetic has to be applied at least one hour before treatment, and is often only partially effective. On the other hand infiltration anesthesia is often associated with discomfort and is not tolerated by patients who are for example needle phobic. In the past years, enhanced and accelerated penetration of various topically applied substances, including photosensitizers, has been proven by pretreatment of the skin with a fractional laser, creating a pattern of microscopic ablation craters.(Haedersdal et al., 2010) This improvement in drug penetration seems to be regardless of ablation crater depth.(Haak et al., 2012) There is limited evidence that transdermal lidocaine absorption can be increased by fractional laser pretreatment.(Oni et al., 2012; Oni et al., 2013) These findings might suggest that local anesthesia of the skin may be achieved by applying an anesthetic drug topically on a skin surface pretreated with a fractional laser. However, little is known about the role of the formulation of the topical drug delivered using this method. Objective: The primary objective of this study is to assess the analgesic effect of fractional carbon dioxide laser assisted delivery of two topical anesthetics (articaine hydrochloride 40 mg/ml and epinephrine 10 μg/ml solution (AHES) and EMLA cream) compared to application of these anesthetics without fractional laser pretreatment. The secondary objective is to compare the efficacy of these two different anesthetics, when applied according to the fractional laser drug delivery principle. Study design: Prospective, single blinded, randomized, controlled, within subject, pilot study. Study population: 10 healthy volunteers ≥18 years, who give written informed consent Intervention: In each subject, four test regions on subject's back of 1x1 centimeter will be randomly allocated in a 2x2 design to (1) ablative fractional laser (AFXL) pretreatment (5% density, 2.5 mJ/microbeam) followed by topical application of AHES, (2) AFXL pretreatment followed by application of EMLA cream, (3) sham AFXL followed by application of AHES on the intact skin and (4) sham AFXL followed by application of EMLA cream on the intact skin. Sham AFXL will be done by delivering an AFXL pass at 5% density and 2.5 mJ/microbeam right adjacent to the region of AHES or EMLA application on the intact skin. After ten minutes incubation time, an AFXL pass will be given as a pain stimulus at each test region with 5% density and 35 mJ/microbeam. Subjects will be asked to indicate pain on a visual analogue scale (VAS) from 0-10 (0: no pain; 10: worst imaginable pain) directly after each pain stimulus.

Official Title
-----------------
Fractional Carbon Dioxide Laser Assisted Delivery of Topical Anesthetics: a Randomized Controlled Pilot Study

Conditions
-----------------
Local Anesthesia of the Skin.

Intervention / Treatment
-----------------
* Device: AFXL
* Drug: AHES
* Drug: EMLA cream


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Fitzpatrick skin type I or II Age ≥18 years Patient is willing and able to give written informed consent Exclusion Criteria: History of keloid or hypertrophic scar formation or complicated wound healing Presence of any active skin disease Known allergy to local anesthesia Pregnancy or lactation Incompetency to understand what the procedure involves Current complaints of chronic pain or other alterations in pain sensation (e.g. due to diabetes mellitus or lepra) Current treatment with systemic analgesics or other medication that can influence pain sensation Current treatment with anticoagulants Fitzpatrick skin type III-VI Excessive sun tan

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: AFXL + AHES<br>This test region will be pretreated with a fractional carbon dioxide laser (ablative fractional laser; AFXL) with a 120 μm spot at 5% density and a pulse energy of 2.5 mJ/microbeam, single pulse at t0 in a subject blinded fashion. Articaine hydrochloride 40 mg/ml and epinephrine 10 μg/ml solution (AHES) will be applied at this test region at t1.Ten minutes after AHES application (incubation time; under occlusion), a pain stimulus will be given at t11 to the subject at the test region using AFXL at 5% density and 35 mJ/microbeam. | Device: AFXL<br>* Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density<br>* Other names: UltraPulse®, DeepFx handpiece; Lumenis Inc.;Drug: AHES<br>* Topical application at test region 1 and 3 under occlusion for 10 minutes<br>* Other names: articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml;|
| Experimental: 2: AFXL + EMLA<br>This test region will be pretreated with a fractional carbon dioxide laser (ablative fractional laser; AFXL) with a 120 μm spot at 5% density and a pulse energy of 2.5 mJ/microbeam, single pulse at t0 in a subject blinded fashion. Eutectic mixture of lidocaine 25 mg/g and prilocaine 25 mg/g cream (EMLA cream) will be applied at this test region at t1.Ten minutes after EMLA cream application (incubation time; under occlusion), a pain stimulus will be given at t11 to the subject at the test region using AFXL at 5% density and 35 mJ/microbeam. | Device: AFXL<br>* Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density<br>* Other names: UltraPulse®, DeepFx handpiece; Lumenis Inc.;Drug: EMLA cream<br>* Topical application at test region 2 and 4 under occlusion for 10 minutes<br>* Other names: lidocaine 25 mg/g + prilocaine 25 mg/g cream;|
| Sham Comparator: 3: Sham AFXL + AHES<br>A pass with a fractional carbon dioxide laser with a 120 μm spot at 5% density and a pulse energy of 2.5 mJ/microbeam, single pulse will be given at the area right adjacent to this test region (sham AFXL) at t0 in a subject blinded fashion. Articaine hydrochloride 40 mg/ml and epinephrine 10 μg/ml solution (AHES) will then be applied at this test region on the intact skin at t1. Ten minutes after AHES application (incubation time; under occlusion), a pain stimulus will be given at t11 to the subject at the test region using AFXL at 5% density and 35 mJ/microbeam. | Device: AFXL<br>* Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density<br>* Other names: UltraPulse®, DeepFx handpiece; Lumenis Inc.;Drug: AHES<br>* Topical application at test region 1 and 3 under occlusion for 10 minutes<br>* Other names: articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml;|
| Sham Comparator: 4: Sham AFXL + EMLA<br>A pass with a fractional carbon dioxide laser with a 120 μm spot at 5% density and a pulse energy of 2.5 mJ/microbeam, single pulse will be given at the area right adjacent to this test region (sham AFXL) at t0 in a subject blinded fashion. Eutectic mixture of lidocaine 25 mg/g and prilocaine 25 mg/g cream (EMLA cream) will then be applied at this test region on the intact skin at t1. Ten minutes after EMLA cream application (incubation time; under occlusion), a pain stimulus will be given at t11 to the subject at the test region using AFXL at 5% density and 35 mJ/microbeam. | Device: AFXL<br>* Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density<br>* Other names: UltraPulse®, DeepFx handpiece; Lumenis Inc.;Drug: EMLA cream<br>* Topical application at test region 2 and 4 under occlusion for 10 minutes<br>* Other names: lidocaine 25 mg/g + prilocaine 25 mg/g cream;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain score | The main study parameter is pain, as scored on a VAS from 0-10 (0: no pain; 10: worst imaginable pain) directly after each pain stimulus. | Directly after pain stimulus. After 10 minutes incubation time of the anesthetics. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fractional laser, Topical anesthesia, Drug delivery