Role of Epoxy-eicosatrienoic Acids in Post-occlusive Hyperemia and Thermal Hyperemia

University Hospital, Grenoble20 enrolled

Overview

The objective of this proof of concept study is to assess the involvement of epoxy-eicosatrienoic acids (EETs) in post-occlusive hyperemic and thermal hyperemia responses, and the interaction between nitric oxide (NO) and EETs, using the latest methods for the study of functional microcirculation.

The EETY study is a single-center proof of concept study in healthy volunteers. The main objective is to study the involvement of epoxy-eicosatrienoic acids (EETs) in the reactivity of cutaneous microcirculation during post-occlusive hyperemia and thermal hyperemia, by studying the response to microdialysis of fluconazole (an inhibitor of EETs) versus control, on the forearm. Response is measured by the amplitude of the post-occlusive hyperemia and thermal hyperemia peaks (maximum amplitude as a percentage of maximal vasodilation and areas under the curve: AUC) during the injection of fluconazole compared to an intradermal injection of solvent (NaCl 9 ‰). The subjects are healthy volunteers of both sexes, aged between 18 and 35, non-smokers and in good health. Over two years, 30 subjects will be included in the study for 6 to 13 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

NONE

Enrollment

Conditions

Healthy Volunteers

Interventions

Microdialysis of fluconazole, vehicle and N(G)-nitro-L-arginine-methyl ester (L-NMMA)DRUG

At the first three visits, volunteers will receive fluconazole (650µmol/L and 6.5mmol/L) and vehicle (NaCl 0.9%), and at the fourth, these plus L-NMMA (10mmol/L), delivered by microdialysis in the forearm, with or without anesthesia. Then post-occlusive hyperemia and thermal hyperemia are performed.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age between 18 and 35 years * Affiliated to the French social security system or beneficiary a similar regime * In good health Exclusion Criteria: * Active smoker * Pregnant, parturient, breast-feeding * Person deprived of civil liberties by judicial or administrative measure; person under legal protection, * Minor less than 18 years * Within period exclusion for other clinical research studies * Person has exceeded the annual compensation for participation in trials * Person with active disease or with prolonged treatment, excluding oral contraceptives and paracetamol * Asthma, urticaria, angioedema, known drug allergy

Locations (1)

Clinical Pharmacology Unit

Grenoble, France

Outcomes

Primary Outcomes

Amplitude of the post-occlusive hyperemia and thermal hyperemia following the injection by intradermal microdialysis of fluconazole compared with injection of vehicle (NaCl 9 ‰)

maximum amplitude as a percentage of maximal vasodilation and area under the curve: AUC

Time frame: 2 hours

Secondary Outcomes

Amplitude of the post-occlusive hyperemia and thermal hyperemia following the injection by intradermal microdialysis of fluconazole, at 2 concentrations, or vehicle (NaCl 9 ‰)

maximum amplitude expressed as percentage of maximal vasodilation and AUC

Time frame: 2 hours

Amplitude of the post-occlusive hyperemia and thermal hyperemia following the injection by intradermal microdialysis of fluconazole or vehicle (NaCl 9 ‰), with and without ANESDERM ® (lidocaine, prilocaine)

maximum amplitude expressed as percentage of maximal vasodilation and AUC

Time frame: 2 hours

Amplitude of the post-occlusive hyperemia and thermal hyperemia following the injection by intradermal microdialysis of fluconazole or vehicle (NaCl 9 ‰), with and without N(G)-nitro-L-arginine-methyl ester (L-NMMA)

maximum amplitude expressed as percentage of maximal vasodilation and AUC

Time frame: 2 hours

Data from ClinicalTrials.gov

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