Fentanyl Ultra Low Doses Effects on the Nociceptive Threshold (FENTANULD)

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT00454259
First received: March 29, 2007
Last updated: August 19, 2008
Last verified: March 2007
  Purpose

Exaggerated pain and hyperalgesia are major issues after surgery and can lead to chronic pain. Opioid are parts of pain sensitization processes but remain absolutely necessary in the intraoperative period. NMDA receptor antagonists succeed in reducing this pain sensitization process. Recent studies show that in pain and opioid-experienced rats (POER) fentanyl ultra low doses do not induce analgesia, as observed in naive rats, but hyperalgesia. This is the first demonstration that a drug can induce opposite effect depending on individual history. We also observed a strong correlation between this hyperalgesic response in POER and the intensity of hyperalgesia they develop later, after inflammatory or surgical pain. The main aim of this study is to measure the dose effect response to fentanyl "ultra low doses" on human volunteer's nociceptive threshold, to determine if such an opposite response profile can be revealed.


Condition Intervention Phase
Pain, Postoperative
Drug: Fentanyl/Placebo injection
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: Fentanyl Ultra Low Doses Effects on Human Volunteer's Nociceptive Threshold. Towards a Simple Pharmacological Test Able to Predict Pain Vulnerability, Post Operative Hyperalgesia Development Risk?

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Nociceptive threshold evaluated with sternal electronical Von Frey mechanical stimulation. The stimulation will increase until the volunteer presses a trigger when the stimulation becomes painful. [ Time Frame: 5 min after injection, and every 15 min during 1 hour ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Non invasive blood pressure (SBP, DBP), heart rate, respiratory rate, pulse oxymetry and cognitive functions evaluation (sedation score). [ Time Frame: all along the experimentation ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: March 2007
Study Completion Date: August 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
0,5 µg/kg
Drug: Fentanyl/Placebo injection
Ultra low dose intravenous injection
Experimental: 2
0,05 µg/kg
Drug: Fentanyl/Placebo injection
Ultra low dose intravenous injection
Experimental: 3
0,005 µg/kg
Drug: Fentanyl/Placebo injection
Ultra low dose intravenous injection
Placebo Comparator: 4
NaCl 0,9 %
Drug: Fentanyl/Placebo injection
Ultra low dose intravenous injection

Detailed Description:
  • Principal Objective : "Evaluate fentanyl "ultra low doses" effects on human volunteer's nociceptive threshold depending on their prior pain and opioid experience."
  • Secondary Objective : "Confirm the innocuousness of this test (the 3 "ultra low doses" used in this trial will be 10 to 1,000 fold lower than low doses use for anesthesia and analgesia) and to find the fentanyl ultra low dose that could be used to develop a pain sensitisation predictive test."
  • Study design : Bicentric, prospective, randomized, double-blind study.

Inclusion criteria :

In both groups:

  • 18-40 years old male volunteer
  • weight: 60 to 85 kg
  • ASA score: 1
  • Informed consent obtained from the patient
  • Gender : Male

In "operated" group:

- At least one history of peripheral surgery under general anesthesia with opioid in the past five years

Exclusion criteria :

In both groups:

  • The patient do not accept inclusion to the study
  • Drug or alcohol abuse history
  • Chronic use of analgesic drugs or history of chronic pain
  • Analgesic or opioid consumption within the 12hs preceding the fentanyl or placebo injection
  • Neurological and/or psychiatric disorder, inability to give informed consent
  • Psychological trauma within the two year preceding the inclusion
  • Any contraindication to fentanyl use
  • Use of any medication interacting with fentanyl
  • Exclusion period from the national healthy volunteer register
  • Gender : Female

In "healthy" group:

- Any history of general anesthesia or surgery

  • Study plan: comparing two groups that only defer by their surgical and opioid prior experience and will receive three fentanyl ultra low doses (10 to 1,000 fold lower than low doses use for anesthesia and analgesia) and placebo (cross over administration, one week wash out period).
  • Number of subjects : 48
  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

In both groups:

  • 18-40 years old male volunteer
  • Weight: 60 to 85 kg
  • ASA score: 1
  • Informed consent obtained from the patient

In "operated" group:

  • At least one history of peripheral surgery under general anesthesia with opioid in the past five years.

Exclusion Criteria:

In both groups:

  • The patients do not accept inclusion to the study
  • Drug or alcohol abuse history
  • Chronic use of analgesic drugs or history of chronic pain
  • Analgesic or opioid consumption within the 12hs preceding the fentanyl or placebo injection
  • Neurological and/or psychiatric disorder, inability to give informed consent
  • Psychological trauma within the two year preceding the inclusion
  • Any contraindication to fentanyl use
  • Use of any medication interacting with fentanyl
  • Exclusion period from the national healthy volunteer register

In "healthy" group:

  • Any history of general anesthesia or surgery
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00454259

Locations
France
CHU de Bordeaux Département d'Anesthésie-Réanimation II
PESSAC Cedex, Hôpital cardiologique, France, 33604
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Study Director: Philippe RICHEBE, Dr University Hospital, Bordeaux
Principal Investigator: Gérard JANVIER, PHD University Hospital, Bordeaux
Principal Investigator: Claude DUBRAY, PHD University Hospital, Bordeaux
Principal Investigator: Alain ESCHALIER, PHD University Hospital, Bordeaux
Principal Investigator: jean DUALE CHRISTIAN, Dr University Hospital, Bordeaux
Principal Investigator: Gisèle PICKERING, Dr University Hospital, Bordeaux
  More Information

Publications:

Responsible Party: Jean-Pierre LEROY / Clinical Research and Innovation Director, University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT00454259     History of Changes
Other Study ID Numbers: CHUBX 2006/08
Study First Received: March 29, 2007
Last Updated: August 19, 2008
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Postoperative Hyperalgesia
Human volunteer
Fentanyl
Randomized Controlled Trial
Pain chronicisation
Predictive test

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Fentanyl
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Analgesics, Opioid

ClinicalTrials.gov processed this record on April 17, 2014