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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble
ClinicalTrials.gov Identifier:
NCT01290198
First received: February 3, 2011
Last updated: September 4, 2012
Last verified: September 2012
History of Changes
  Purpose

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.


Condition Intervention
Healthy Volunteers
 Drug: Microdialysis of fluconazole, vehicle and N(G)-nitro-L-arginine-methyl ester (L-NMMA)

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Role of Epoxy-eicosatrienoic Acids in Post-occlusive Hyperemia and Thermal Hyperemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:
  • Amplitude of the post-occlusive hyperemia and thermal hyperemia following the injection by intradermal microdialysis of fluconazole compared with injection of vehicle (NaCl 9 ‰) [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    maximum amplitude as a percentage of maximal vasodilation and area under the curve: AUC


Secondary Outcome Measures:
  • Amplitude of the post-occlusive hyperemia and thermal hyperemia following the injection by intradermal microdialysis of fluconazole, at 2 concentrations, or vehicle (NaCl 9 ‰) [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    maximum amplitude expressed as percentage of maximal vasodilation and AUC

  • 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) [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    maximum amplitude expressed as percentage of maximal vasodilation and AUC

  • 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) [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    maximum amplitude expressed as percentage of maximal vasodilation and AUC


Enrollment: 20
Study Start Date: February 2011
Study Completion Date: May 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01290198

Locations
France
Clinical Pharmacology Unit
Grenoble, France, 38000
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
Principal Investigator: Jean-Luc Cracowski, MD,PhD University Hospital, Grenoble
  More Information

No publications provided

Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT01290198     History of Changes
Other Study ID Numbers: DCIC 10 01
Study First Received: February 3, 2011
Last Updated: September 4, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Grenoble:
epoxy-eicosatrienoic acid
Laser Doppler
Endothelium derived hyperpolarizing factor
cutaneous microcirculation
 post-occlusive hyperaemia
thermal hyperemia
intradermal microdialysis
fluconazole

Additional relevant MeSH terms:
Hyperemia
Vascular Diseases
Cardiovascular Diseases
Fluconazole
Omega-N-Methylarginine
NG-Nitroarginine Methyl Ester
Antifungal Agents
 Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013