Fractional Laser Assisted Delivery of Anesthetics

NCT ID: NCT02246179

Last Updated: 2014-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-30

Study Completion Date

2014-10-31

Brief Summary

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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

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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.

Conditions

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Local Anesthesia of the Skin.

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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1: AFXL + AHES

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.

Group Type EXPERIMENTAL

AFXL

Intervention Type DEVICE

Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density

AHES

Intervention Type DRUG

Topical application at test region 1 and 3 under occlusion for 10 minutes

2: AFXL + EMLA

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.

Group Type EXPERIMENTAL

AFXL

Intervention Type DEVICE

Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density

EMLA cream

Intervention Type DRUG

Topical application at test region 2 and 4 under occlusion for 10 minutes

3: Sham AFXL + AHES

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.

Group Type SHAM_COMPARATOR

AFXL

Intervention Type DEVICE

Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density

AHES

Intervention Type DRUG

Topical application at test region 1 and 3 under occlusion for 10 minutes

4: Sham AFXL + EMLA

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.

Group Type SHAM_COMPARATOR

AFXL

Intervention Type DEVICE

Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density

EMLA cream

Intervention Type DRUG

Topical application at test region 2 and 4 under occlusion for 10 minutes

Interventions

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AFXL

Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density

Intervention Type DEVICE

AHES

Topical application at test region 1 and 3 under occlusion for 10 minutes

Intervention Type DRUG

EMLA cream

Topical application at test region 2 and 4 under occlusion for 10 minutes

Intervention Type DRUG

Other Intervention Names

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Fractional carbon dioxide laser Ablative fractional laser Fractional CO2 laser UltraPulse®, DeepFx handpiece; Lumenis Inc. Ultracain D-S forte articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml lidocaine 25 mg/g + prilocaine 25 mg/g cream

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role collaborator

Netherlands Institute for Pigment Disorders

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Albert Wolkerstorfer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Netherlands Institute for Pigment Disorders, Department of Dermatology, Academic Medical Center, University of Amsterdam

Menno A. De Rie, MD, PhD

Role: STUDY_DIRECTOR

Department of Dermatology, Academic Medical Center, University of Amsterdam

Locations

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Netherlands Institute for Pigment disorders

Amsterdam, , Netherlands

Site Status

Countries

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Netherlands

References

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Haedersdal M, Sakamoto FH, Farinelli WA, Doukas AG, Tam J, Anderson RR. Fractional CO(2) laser-assisted drug delivery. Lasers Surg Med. 2010 Feb;42(2):113-22. doi: 10.1002/lsm.20860.

Reference Type BACKGROUND
PMID: 20166154 (View on PubMed)

Haak CS, Farinelli WA, Tam J, Doukas AG, Anderson RR, Haedersdal M. Fractional laser-assisted delivery of methyl aminolevulinate: Impact of laser channel depth and incubation time. Lasers Surg Med. 2012 Dec;44(10):787-95. doi: 10.1002/lsm.22102. Epub 2012 Dec 4.

Reference Type BACKGROUND
PMID: 23212624 (View on PubMed)

Oni G, Brown SA, Kenkel JM. Can fractional lasers enhance transdermal absorption of topical lidocaine in an in vivo animal model? Lasers Surg Med. 2012 Feb;44(2):168-74. doi: 10.1002/lsm.21130. Epub 2012 Feb 2.

Reference Type BACKGROUND
PMID: 22302761 (View on PubMed)

Oni G, Rasko Y, Kenkel J. Topical lidocaine enhanced by laser pretreatment: a safe and effective method of analgesia for facial rejuvenation. Aesthet Surg J. 2013 Aug 1;33(6):854-61. doi: 10.1177/1090820X13496248.

Reference Type BACKGROUND
PMID: 23908302 (View on PubMed)

Ong MW, Bashir SJ. Fractional laser resurfacing for acne scars: a review. Br J Dermatol. 2012 Jun;166(6):1160-9. doi: 10.1111/j.1365-2133.2012.10870.x. Epub 2012 May 8.

Reference Type BACKGROUND
PMID: 22296284 (View on PubMed)

Wolfe JW, Butterworth JF. Local anesthetic systemic toxicity: update on mechanisms and treatment. Curr Opin Anaesthesiol. 2011 Oct;24(5):561-6. doi: 10.1097/ACO.0b013e32834a9394.

Reference Type BACKGROUND
PMID: 21841477 (View on PubMed)

Hahn IH, Hoffman RS, Nelson LS. EMLA-induced methemoglobinemia and systemic topical anesthetic toxicity. J Emerg Med. 2004 Jan;26(1):85-8. doi: 10.1016/j.jemermed.2003.03.003.

Reference Type BACKGROUND
PMID: 14751483 (View on PubMed)

Baron ED, Harris L, Redpath WS, Shapiro H, Hetzel F, Morley G, Bar-Or D, Stevens SR. Laser-assisted penetration of topical anesthetic in adults. Arch Dermatol. 2003 Oct;139(10):1288-90. doi: 10.1001/archderm.139.10.1288.

Reference Type BACKGROUND
PMID: 14568832 (View on PubMed)

Koh JL, Harrison D, Swanson V, Norvell DC, Coomber DC. A comparison of laser-assisted drug delivery at two output energies for enhancing the delivery of topically applied LMX-4 cream prior to venipuncture. Anesth Analg. 2007 Apr;104(4):847-9. doi: 10.1213/01.ane.0000257925.36641.9e.

Reference Type BACKGROUND
PMID: 17377092 (View on PubMed)

Shapiro H, Harris L, Hetzel FW, Bar-Or D. Laser assisted delivery of topical anesthesia for intramuscular needle insertion in adults. Lasers Surg Med. 2002;31(4):252-6. doi: 10.1002/lsm.10101.

Reference Type BACKGROUND
PMID: 12355570 (View on PubMed)

Hantash BM, Bedi VP, Chan KF, Zachary CB. Ex vivo histological characterization of a novel ablative fractional resurfacing device. Lasers Surg Med. 2007 Feb;39(2):87-95. doi: 10.1002/lsm.20405.

Reference Type BACKGROUND
PMID: 17115384 (View on PubMed)

Haak CS, Bhayana B, Farinelli WA, Anderson RR, Haedersdal M. The impact of treatment density and molecular weight for fractional laser-assisted drug delivery. J Control Release. 2012 Nov 10;163(3):335-41. doi: 10.1016/j.jconrel.2012.09.008. Epub 2012 Sep 21.

Reference Type BACKGROUND
PMID: 23000695 (View on PubMed)

Togsverd-Bo K, Haak CS, Thaysen-Petersen D, Wulf HC, Anderson RR, Haedersdal M. Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial. Br J Dermatol. 2012 Jun;166(6):1262-9. doi: 10.1111/j.1365-2133.2012.10893.x.

Reference Type BACKGROUND
PMID: 22348388 (View on PubMed)

Other Identifiers

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NL48655.018.14

Identifier Type: -

Identifier Source: org_study_id