Official Title: “Local Anaesthetic Effects of Transcutaneous Amitriptyline in Human Volunteers : a Controlled, Double-Blinded, Randomised Study Versus Placebo and Transcutaneous Local Anaesthetic (EMLA(R))”

The aim of this study is to assess the local anaesthetic effects of amitriptyline applied on the skin of human volunteers, considering the differential effects on mechanic and thermic sensitivity, the local and general tolerance, and the systemic absorption of the drug. The solution used for dilution of amitriptyline is the only one known to allow transcutaneous absorption of the drug [1]. Considering that the peripheral sensitive fibre is a possible site of action of tricyclic antidepressants for relieving neuropathic pain [2,3], this is a first step study before further assessment of the therapeutic effects of transcutaneous amitriptyline.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study

Sixteen male healthy volunteers are enrolled for this study. They receive in a randomised order on six regions of dorsal skin (after previous targetting by ink marks) the six following treatments : lidocaïne-prilocaïne anaesthetic cream (EMLA (R)), normal saline, amityptiline hydrochloride diluted in solution of water (%), isopropanol (%) , glycerol (%), titrated with sodium hydroxide for pH=8.5, at four different concentrations (0,25, 50 and 100 mM).

The person in charge of local application does not participate to further examination.

Immediately after one hour of application, the volunteer is examined, and then every 2 hours during 8 hours, and 24 hours after the end if application. Every trial includes, for every treated area, (a) measurement of sensitive and nociceptive threshold to Von Frey hair application, (b) assessment of sensation induced by cold and heat after Rolltemp TM application, (c) measurement of sensitive threshold to cold, then sensitive and nociceptive thresholds to heat with Thermotest TM, (d) clinical evaluation of tolerance to the treatment, (e) blood sampling for measuring amitriptylinemia (HPLC). The possible residual anaesthetic effects of the treatment are assessed one and three weeks after the application, by measurement of sensitive and nociceptive threshold to Von Frey hair application. The statistical analysis will use two-way ANOVA, considering the following factors : treatment, time, order, subject, subject/order.

Intervention(s) in this Clinical Trial

• Drug: Amitriptyline

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• history of intolerance to amitriptyline, lidocaine or prilocaine
• cardiac predisposition to intolerance to tricyclic antidepressants

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University Hospital, Clermont-Ferrand

Overall Clinical Trial Officials and Contacts

Claude DUBRAY, Pr Principal Investigator CENTRE DE PHARMACOLOGIE CLINIQUE  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00355277

Study ID Number: CHU63-0014

ClinicalTrials.gov Identifier: NCT00355277

Health Authority: France: Ministry of Health