Fractional Laser Assisted Delivery of Anesthetics III

Study Overview
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Brief Summary
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The purpose of this study is to compare the effect of pretreatment with two different ablative laser modalities, a CO2 laser and an Er:YAG laser, and to assess the role of laser density in fractional laser assisted topical anesthesia.

Detailed Description
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Rationale: In dermatology anesthetics are frequently injected or topically applied to achieve local anesthesia. Injectable anesthetics are effective but uncomfortable during administration, especially for people who are needle phobic. Application of topical anesthesia is painless but time consuming and often only partial aesthesia is achieved due to the barrier function of the stratum corneum. (Manuskiatti, Triwongwaranat et al. 2010) Penetration of local anesthetics could be enhanced by pretreatment of the skin with ablative fractional lasers (AFXL) which locally disrupts the stratum corneum by creating an array of microscopic ablation channels. (Sklar, Burnett et al. 2014) In a previous pilot study, conducted at our institute, we demonstrated that effective anesthesia could be achieved within ten minutes after application of a topical anesthetic on skin pretreated with AFXL at painless settings. (Meesters, Bakker et al. 2015) However, little is still known about the role of the type of fractional laser used (e.g. CO2 or Er:YAG laser), the laser settings, the type of anesthetic and the occlusion time on the efficacy of the anesthesia. Objective: The objectives of this study are to compare the efficacy of pretreatment with two different ablative laser modalities, a CO2 laser and an Er:YAG laser, and to assess the role of laser density in fractional laser assisted topical anesthesia. Study design: Prospective, single blinded, randomized, controlled, within subject, pilot study. Study population: 15 healthy volunteers ≥18 years, who give written informed consent Intervention: In each subject, four test regions on subject's back of 1x1 cm will be randomly allocated to (I) pretreatment with the fractional CO2 laser at 5% density, (II) pretreatment with the fractional CO2 laser at 15% density, (III) pretreatment with the fractional Er:YAG laser at 5% density and (IV) pretreatment with the fractional Er:YAG laser at 15% density. After pretreatment, articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml 30 solution (AHES) will be applied on the test regions with 15 minutes occlusion time. After 15 minutes a pain stimulus, consisting of a pass with the fractional CO2 laser at 50 mJ and 5% density (scanned area 6x6 mm), will be given at each test region. In addition, a reference pain stimulus with the CO2 laser at the same settings will be given at unanesthetized skin. 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
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Parameters in Fractional Laser Assisted Delivery of Topical Anesthetics: Role of Laser Type and Laser Settings

Conditions
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Local Anesthesia of the Skin

Intervention / Treatment
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* Device: Fractional CO2 laser, 2.5 mJ, 5% density
* Device: Fractional CO2 laser, 2.5 mJ, 15% density
* Device: Fractional Er:YAG laser, 9 mJ, 5% density
* Device: Fractional Er:YAG laser, 9 mJ, 15% density
* Device: Fractional CO2 laser, 50 mJ, 5% density
* Drug: AHES


Participation Criteria
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Eligibility Criteria
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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
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fractional CO2 laser at 5% density<br>This test region will be pretreated with a fractional carbon dioxide laser with a 120 μm spot at 5% density and a pulse energy of 2.5 mJ/microbeam (Fractional CO2 laser, 2.5 mJ, 5% density) in a subject blinded fashion. After pretreament Articaine hydrochloride 40 mg/ml and epinephrine 10 μg/ml solution (AHES) will be applied to this test region. Fifteen minutes after AHES application (incubation time; under occlusion), a pain stimulus will be given at the test region with the Fractional CO2 laser, 50 mJ, 5% density. | Device: Fractional CO2 laser, 2.5 mJ, 5% density<br>* Pretreatment at 2.5 mJ/microbeam and 5% density. Pain stimulus at 50 mJ/microbeam and 5% density<br>* Other names: Ablative fractional laser;Device: Fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus at 50 mJ/microbeam and 5% density<br>* Other names: Ablative fractional laser;Drug: AHES<br>* Topical application at test region I-IV under occlusion for 15 minutes<br>* Other names: Articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml;|
| Experimental: Fractional CO2 laser at 15% density<br>This test region will be pretreated with a fractional carbon dioxide laser with a 120 μm spot at 15% density and a pulse energy of 2.5 mJ/microbeam (Fractional CO2 laser, 2.5 mJ, 15% density) in a subject blinded fashion. After pretreament Articaine hydrochloride 40 mg/ml and epinephrine 10 μg/ml solution (AHES) will be applied at this test region. Fifteen minutes after AHES application (incubation time; under occlusion), a pain stimulus will be given at the test region with the Fractional CO2 laser, 50 mJ, 5% density. | Device: Fractional CO2 laser, 2.5 mJ, 15% density<br>* Pretreatment at 2.5 mJ/microbeam and 15% density. Pain stimulus at 50 mJ/microbeam and 5% density<br>* Other names: Ablative fractional laser;Device: Fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus at 50 mJ/microbeam and 5% density<br>* Other names: Ablative fractional laser;Drug: AHES<br>* Topical application at test region I-IV under occlusion for 15 minutes<br>* Other names: Articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml;|
| Experimental: Fractional Er:YAG laser at 5% density<br>This test region will be pretreated with a Erbium Yttrium Aluminum Garnet laser with a 225 μm spot at 5% density and a pulse energy of 9 mJ/microbeam (Fractional Er:YAG laser, 9 mJ, 5% density) in a subject blinded fashion. After pretreatment Articaine hydrochloride 40 mg/ml and epinephrine 10 μg/ml solution (AHES) will be applied at this test region. Fifteen minutes after AHES application (incubation time; under occlusion), a pain stimulus will be given at the test region with the Fractional CO2 laser, 50 mJ, 5% density. | Device: Fractional Er:YAG laser, 9 mJ, 5% density<br>* Pretreatment at 9 mJ and 5% density.<br>* Other names: Ablative fractional laser;Device: Fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus at 50 mJ/microbeam and 5% density<br>* Other names: Ablative fractional laser;Drug: AHES<br>* Topical application at test region I-IV under occlusion for 15 minutes<br>* Other names: Articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml;|
| Experimental: Fractional Er:YAG laser at 15% density<br>This test region will be pretreated with a Erbium Yttrium Aluminum Garnet laser with a 225 μm spot at 15% density and a pulse energy of 9 mJ/microbeam (Fractional Er:YAG laser, 9 mJ, 15% density) in a subject blinded fashion. After pretreatment Articaine hydrochloride 40 mg/ml and epinephrine 10 μg/ml solution (AHES) will be applied at this test region. Fifteen minutes after AHES application (incubation time; under occlusion), a pain stimulus will be given at the test region with the Fractional CO2 laser, 50 mJ, 5% density. | Device: Fractional Er:YAG laser, 9 mJ, 15% density<br>* Pretreatment at 9 mJ and 15% density.<br>* Other names: Ablative fractional laser;Device: Fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus at 50 mJ/microbeam and 5% density<br>* Other names: Ablative fractional laser;Drug: AHES<br>* Topical application at test region I-IV under occlusion for 15 minutes<br>* Other names: Articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml;|

What is the study measuring?
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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). | After 15 minutes incubation time of the anesthetics | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain score | The secondary study parameter is pain, as scored on a VAS from 0-10 (0: no pain; 10: worst imaginable pain) directly after pretreatment | Directly after pretreatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fractional laser, Topical anesthesia, Drug delivery, CO2 laser, Er:YAG laser