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

NCT ID: NCT01290198

Last Updated: 2012-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2012-05-31

Brief Summary

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.

Detailed Description

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.

Conditions

Healthy Volunteers

Keywords

epoxy-eicosatrienoic acid; Laser Doppler; Endothelium derived hyperpolarizing factor; cutaneous microcirculation; post-occlusive hyperaemia; thermal hyperemia; intradermal microdialysis; fluconazole

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Study Groups

Vehicle without ANESDERM (lidocaine, prilocaine)

Group Type: PLACEBO_COMPARATOR

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

Intervention Type: 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.

Vehicle with ANESDERM (lidocaine, prilocaine)

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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.

Fluconazole without ANESDERM (lidocaine, prilocaine)

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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.

Fluconazole with ANESDERM (lidocaine, prilocaine)

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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.

Interventions

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

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Luc Cracowski, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

Locations

Clinical Pharmacology Unit

Grenoble, , France

Countries

France

Other Identifiers

DCIC 10 01

Identifier Type: -

Identifier Source: org_study_id