Fractional Laser Assisted Delivery of Anesthetics IIIb

Study Overview
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Brief Summary
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The purpose of this study are to compare the efficacy of two different commercially available local anesthetics on AFXL pretreated skin and to assess the role of the application time in this technique.

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 anesthetic the type of anesthetic and the application time on the efficacy of the anesthesia. Objective: The objective of this study is to compare the efficacy of two different commercially available local anesthetics on AFXL pretreated skin, a low concentration articaine solution and a high concentration lidocaine/tetracaine cream. We also aim to compare the efficacy of AFXL assisted topical anesthesia after various different application times. 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, six test regions on subject's back of 1x1 cm will be pretreated with the fractional carbon dioxide (CO2) laser at 2.5 mJ and 15% density and will be randomly allocated to application of (I) articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml 30 solution (AHES) (5 minutes application time), (II) AHES (15 minutes application time), (III) AHES (25 minutes application time), (IV) lidocaine 70 mg/g + tetracaine 70 mg/g cream (LTC) (5 minutes application time, (V) LTC (15 minutes application time), (VI) LTC (25 minutes application 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 Anesthetic and Application Time

Conditions
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Local Anesthesia of the Skin

Intervention / Treatment
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* Drug: AHES 5 minutes
* Drug: AHES 15 minutes
* Drug: AHES 25 minutes
* Drug: LTC 5 minutes
* Drug: LTC 15 minutes
* Drug: LTC 25 minutes
* Device: fractional CO2 laser, 50 mJ, 5% density


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: AHES 5 minutes<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 pretreatment articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml solution (AHES) will be applied at this test region. 5 minutes after AHES application (under occlusion), a pain stimulus will be given at the test region with the fractional CO2 laser, 50 mJ, 5% density. | Drug: AHES 5 minutes<br>* Topical application of AHES with 5 minutes application time After 5 minutes: pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml;Device: fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Ablative fractional laser;|
| Experimental: AHES 15 minutes<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 pretreatment articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml solution (AHES) will be applied at this test region. 15 minutes after AHES application (under occlusion), a pain stimulus will be given at the test region with the fractional CO2 laser, 50 mJ, 5% density. | Drug: AHES 15 minutes<br>* Topical application of AHES with 15 minutes application time After 15 minutes: pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml;Device: fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Ablative fractional laser;|
| Experimental: AHES 25 minutes<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 pretreatment articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml solution (AHES) will be applied at this test region. 25 minutes after AHES application (under occlusion), a pain stimulus will be given at the test region with the fractional CO2 laser, 50 mJ, 5% density. | Drug: AHES 25 minutes<br>* Topical application of AHES with 25 minutes application time After 25 minutes: pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml;Device: fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Ablative fractional laser;|
| Experimental: LTC 5 minutes<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 pretreatment lidocaine 70 mg/g + tetracaine 70 mg/g cream (LTC) will be applied at this test region. 5 minutes after LTC application (under occlusion), a pain stimulus will be given at the test region with the fractional CO2 laser, 50 mJ, 5% density. | Drug: LTC 5 minutes<br>* Topical application of LTC with 5 minutes application time After 5 minutes: pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Lidocaine 70 mg/g + tetracaine 70 mg/g cream;Device: fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Ablative fractional laser;|
| Experimental: LTC 15 minutes<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 pretreatment lidocaine 70 mg/g + tetracaine 70 mg/g cream (LTC) will be applied at this test region. 15 minutes after LTC application (under occlusion), a pain stimulus will be given at the test region with the fractional CO2 laser, 50 mJ, 5% density. | Drug: LTC 15 minutes<br>* Topical application of LTC with 15 minutes application time After 15 minutes: pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Lidocaine 70 mg/g + tetracaine 70 mg/g cream;Device: fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Ablative fractional laser;|
| Experimental: LTC 25 minutes<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 pretreatment lidocaine 70 mg/g + tetracaine 70 mg/g cream (LTC) will be applied at this test region. 25 minutes after LTC application (under occlusion), a pain stimulus will be given at the test region with the fractional CO2 laser, 50 mJ, 5% density. | Drug: LTC 25 minutes<br>* Topical application of LTC with 25 minutes application time After 25 minutes: pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Lidocaine 70 mg/g + tetracaine 70 mg/g cream;Device: fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Ablative fractional laser;|
| Other: Unanesthetized skin<br>A pain stimulus will be given at unanesthetized skin with the fractional CO2 laser, 50 mJ, 5% density | Device: fractional CO2 laser, 50 mJ, 5% density<br>* Pain stimulus with the fractional CO2 laser, 50 mJ, 5% density<br>* Other names: Ablative fractional laser;|

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 5 minutes application time of the anesthetics | 
| 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 application time of the anesthetics | 
| Pain score | The main study parameter is pain, as scored on a VAS from 0-10 (0: no pain; 10: worst imaginable pain). | After 25 minutes application 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