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

May 11, 2026 updated by: University Hospital, Bordeaux

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?

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Hôpital Cardiologique
      • Pessac, Hôpital Cardiologique, France, 33604
        • CHU de Bordeaux Département d'Anesthésie-Réanimation II

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 36 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
5 min after injection, and every 15 min during 1 hour

Secondary Outcome Measures

Outcome Measure
Time Frame
Non invasive blood pressure (SBP, DBP), heart rate, respiratory rate, pulse oxymetry and cognitive functions evaluation (sedation score).
Time Frame: all along the experimentation
all along the experimentation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

August 1, 2007

Study Completion (Actual)

August 1, 2007

Study Registration Dates

First Submitted

March 29, 2007

First Submitted That Met QC Criteria

March 29, 2007

First Posted (Estimated)

March 30, 2007

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 11, 2026

Last Verified

March 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2006/08
  • 2006-006847-30 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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