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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Microdialysis of fluconazole, vehicle and N(G)-nitro-L-arginine-methyl ester (L-NMMA)

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38000
    • Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vehicle without ANESDERM (lidocaine, prilocaine)	Drug: 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.
Active Comparator: Vehicle with ANESDERM (lidocaine, prilocaine)	Drug: 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.
Active Comparator: Fluconazole without ANESDERM (lidocaine, prilocaine)	Drug: 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.
Active Comparator: Fluconazole with ANESDERM (lidocaine, prilocaine)	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	2 hours

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Jean-Luc Cracowski, MD,PhD, University Hospital, Grenoble

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: February 3, 2011
• First Submitted That Met QC Criteria: February 3, 2011
• First Posted (Estimate): February 4, 2011

Study Record Updates

• Last Update Posted (Estimate): September 5, 2012
• Last Update Submitted That Met QC Criteria: September 4, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: post-occlusive hyperaemia; fluconazole; intradermal microdialysis; Laser Doppler; cutaneous microcirculation; epoxy-eicosatrienoic acid; Endothelium derived hyperpolarizing factor; thermal hyperemia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hyperemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole; NG-Nitroarginine Methyl Ester
• Other Study ID Numbers: DCIC 10 01