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

University Hospital of Bordeaux

Status and phase: Completed; Phase 4

Conditions: Pain, Postoperative

Treatments: Drug: Fentanyl/Placebo injection

Study type: Interventional

Funder types: Other

Identifiers

NCT00454259

CHUBX 2006/08

Details and patient eligibility

About

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.

Full 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

Enrollment: 48 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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48 participants in 4 patient groups, including a placebo group

1

Experimental group

Description:

0,5 µg/kg

Treatment:

Drug: Fentanyl/Placebo injection

2

Experimental group

Description:

0,05 µg/kg

Treatment:

Drug: Fentanyl/Placebo injection

3

Experimental group

Description:

0,005 µg/kg

Treatment:

Drug: Fentanyl/Placebo injection

4

Placebo Comparator group

Description:

NaCl 0,9 %

Treatment:

Drug: Fentanyl/Placebo injection