Fractional Laser Assisted Delivery of Anesthetics

Local Anesthesia of the Skin. Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02246179
• Other study ID #: NL48655.018.14
• Status: Completed
• Phase: Phase 4
• First received: September 12, 2014
• Last updated: November 7, 2014
• Start date: September 2014
• Est. completion date: October 2014

Study information

• Verified date: November 2014
• Source: Netherlands Institute for Pigment Disorders
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Local Anesthesia of the Skin.

Intervention

Device:
• AFXL
Pretreatment at 2.5 mJ/microbeam and 5% density Pain stimulus at 35 mJ/microbeam and 5% density

Drug:
• AHES
Topical application at test region 1 and 3 under occlusion for 10 minutes
• EMLA cream
Topical application at test region 2 and 4 under occlusion for 10 minutes

Locations

Country	Name	City	State
Netherlands	Netherlands Institute for Pigment disorders	Amsterdam

Sponsors (2)

Lead Sponsor	Collaborator
Netherlands Institute for Pigment Disorders	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. Erratum in: Lasers Surg Med. 2013 Nov;45(9):617. — View Citation

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. — View Citation

Hahn IH, Hoffman RS, Nelson LS. EMLA-induced methemoglobinemia and systemic topical anesthetic toxicity. J Emerg Med. 2004 Jan;26(1):85-8. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Togsverd-Bo K, Haak CS, Thaysen-Petersen D, Wulf HC, Anderson RR, Hædersdal 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. Erratum in: Br J Dermatol. 2012 Aug;167(2):461. Hædesdal, M [corrected to Hædersdal, M]. — View Citation

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. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No