Pain, PostoperativePhase 4FENTANULDNCT00454259

Fentanyl Ultra Low Doses Effects on the Nociceptive Threshold

A Phase 4 study of Pain, Postoperative, run by University Hospital, Bordeaux at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 40 years, men onlyHealthy volunteers can take part
Conditions the study is for: Pain, Postoperative
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 48 participants
Where: 1 siteFrance
Study dates: Mar 2007to Aug 2007
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 40 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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

Show all 12Show fewer

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 locations and contacts

1 site in 1 country.

France1 site

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

Other trials in France

About this study

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?

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.

Read the 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

Conditions: Pain, Postoperative
Being tested: Fentanyl/Placebo injection
Keywords: Postoperative Hyperalgesia, Human volunteer, Fentanyl, Randomized Controlled Trial, Pain chronicisation, Predictive test
Medical subject headings: Pain, Postoperative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Fentanyl/Placebo injectionDrug
Ultra low dose intravenous injection

Study groups in NCT00454259
Study group	Role	What they receive
1	Experimental	0,5 µg/kg Receives: Drug: Fentanyl/Placebo injection
2	Experimental	0,05 µg/kg Receives: Drug: Fentanyl/Placebo injection
3	Experimental	0,005 µg/kg Receives: Drug: Fentanyl/Placebo injection
4	Placebo comparator	NaCl 0,9 % Receives: Drug: Fentanyl/Placebo injection

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 5 min after injection, and every 15 min during 1 hour

Secondary outcomes (1)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2007Aug 2007

First posted30 Mar 2007 (estimated)
Study startMar 2007
Primary completionAug 2007
Study completionAug 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (13)Papers the sponsor has linked to this study.
Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Health services research
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00454259
Sponsor's protocol ID: CHUBX 2006/08
Other IDs: 2006-006847-30
Acronym: FENTANULD
Status last verified: Mar 2007
First submitted: 29 Mar 2007
Last updated: 14 May 2026
Results posted: No
Data monitoring committee: Yes

Publications

Hsu YW, Somma J, Hung YC, Tsai PS, Yang CH, Chen CC. Predicting postoperative pain by preoperative pressure pain assessment. Anesthesiology. 2005 Sep;103(3):613-8. doi: 10.1097/00000542-200509000-00026.
PubMed 16129988
Kalkman JC, Visser K, Moen J, Bonsel JG, Grobbee ED, Moons MKG. Preoperative prediction of severe postoperative pain. Pain. 2003 Oct;105(3):415-423. doi: 10.1016/S0304-3959(03)00252-5.
PubMed 14527702
Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology. 2000 Oct;93(4):1123-33. doi: 10.1097/00000542-200010000-00038. No abstract available.
PubMed 11020770
Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.
PubMed 16698416
Celerier E, Laulin JP, Corcuff JB, Le Moal M, Simonnet G. Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration: a sensitization process. J Neurosci. 2001 Jun 1;21(11):4074-80. doi: 10.1523/JNEUROSCI.21-11-04074.2001.
PubMed 11356895
Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain. 1993 Mar;52(3):259-285. doi: 10.1016/0304-3959(93)90161-H.
PubMed 7681556
Shen KF, Crain SM. Cholera toxin-B subunit blocks excitatory effects of opioids on sensory neuron action potentials indicating that GM1 ganglioside may regulate Gs-linked opioid receptor functions. Brain Res. 1990 Oct 29;531(1-2):1-7. doi: 10.1016/0006-8993(90)90751-v.
PubMed 1981160
Crain SM, Shen KF. Modulation of opioid analgesia, tolerance and dependence by Gs-coupled, GM1 ganglioside-regulated opioid receptor functions. Trends Pharmacol Sci. 1998 Sep;19(9):358-65. doi: 10.1016/s0165-6147(98)01241-3.
PubMed 9786023
Richebe P, Rivat C, Laulin JP, Maurette P, Simonnet G. Ketamine improves the management of exaggerated postoperative pain observed in perioperative fentanyl-treated rats. Anesthesiology. 2005 Feb;102(2):421-8. doi: 10.1097/00000542-200502000-00028.
PubMed 15681961
Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472):1765-9. doi: 10.1126/science.288.5472.1765.
PubMed 10846153
Rivat C, Laulin JP, Corcuff JB, Celerier E, Pain L, Simonnet G. Fentanyl enhancement of carrageenan-induced long-lasting hyperalgesia in rats: prevention by the N-methyl-D-aspartate receptor antagonist ketamine. Anesthesiology. 2002 Feb;96(2):381-91. doi: 10.1097/00000542-200202000-00025.
PubMed 11818772
Simonnet G, Rivat C. Opioid-induced hyperalgesia: abnormal or normal pain? Neuroreport. 2003 Jan 20;14(1):1-7. doi: 10.1097/00001756-200301200-00001. No abstract available.
PubMed 12544821
Richebe P, Capdevila X, Rivat C. Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations. Anesthesiology. 2018 Sep;129(3):590-607. doi: 10.1097/ALN.0000000000002238.
PubMed 29738328

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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?
ClinicalTrials.gov ID: NCT00454259
Acronym / sponsor ID: FENTANULD / CHUBX 2006/08
Conditions: Pain, Postoperative
Keywords: Postoperative Hyperalgesia, Human volunteer, Fentanyl, Randomized Controlled Trial, Pain chronicisation, Predictive test
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: University Hospital, BordeauxUniversity, hospital or other
Study start: Mar 2007
Primary completion: Aug 2007 (actual)
Study completion: Aug 2007 (actual)
First posted: 30 Mar 2007 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Health services research
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
1	Experimental	Drug: Fentanyl/Placebo injection0,5 µg/kg
2	Experimental	Drug: Fentanyl/Placebo injection0,05 µg/kg
3	Experimental	Drug: Fentanyl/Placebo injection0,005 µg/kg
4	Placebo comparator	Drug: Fentanyl/Placebo injectionNaCl 0,9 %

Who may qualify

Ages: 18 to 40 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

18-40 years old male volunteer
Weight: 60 to 85 kg
ASA score: 1
Informed consent obtained from the patient
At least one history of peripheral surgery under general anesthesia with opioid in the past five years.

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Fentanyl/Placebo injectionUltra low dose intravenous injection	Drug	1, 2, 3, 4

Primary outcome

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

1 secondary outcome

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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
Background: PubMed 16129988Hsu YW, Somma J, Hung YC, Tsai PS, Yang CH, Chen CC. Predicting postoperative pain by preoperative pressure pain assessment. Anesthesiology. 2005 Sep;103(3):613-8. doi: 10.1097/00000542-200509000-00026.
Background: PubMed 14527702Kalkman JC, Visser K, Moen J, Bonsel JG, Grobbee ED, Moons MKG. Preoperative prediction of severe postoperative pain. Pain. 2003 Oct;105(3):415-423. doi: 10.1016/S0304-3959(03)00252-5.
Background: PubMed 11020770Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology. 2000 Oct;93(4):1123-33. doi: 10.1097/00000542-200010000-00038. No abstract available.
Background: PubMed 16698416Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.
Background: PubMed 11356895Celerier E, Laulin JP, Corcuff JB, Le Moal M, Simonnet G. Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration: a sensitization process. J Neurosci. 2001 Jun 1;21(11):4074-80. doi: 10.1523/JNEUROSCI.21-11-04074.2001.
Background: PubMed 7681556Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain. 1993 Mar;52(3):259-285. doi: 10.1016/0304-3959(93)90161-H.
Background: PubMed 1981160Shen KF, Crain SM. Cholera toxin-B subunit blocks excitatory effects of opioids on sensory neuron action potentials indicating that GM1 ganglioside may regulate Gs-linked opioid receptor functions. Brain Res. 1990 Oct 29;531(1-2):1-7. doi: 10.1016/0006-8993(90)90751-v.
Background: PubMed 9786023Crain SM, Shen KF. Modulation of opioid analgesia, tolerance and dependence by Gs-coupled, GM1 ganglioside-regulated opioid receptor functions. Trends Pharmacol Sci. 1998 Sep;19(9):358-65. doi: 10.1016/s0165-6147(98)01241-3.
Background: PubMed 15681961Richebe P, Rivat C, Laulin JP, Maurette P, Simonnet G. Ketamine improves the management of exaggerated postoperative pain observed in perioperative fentanyl-treated rats. Anesthesiology. 2005 Feb;102(2):421-8. doi: 10.1097/00000542-200502000-00028.
Background: PubMed 10846153Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472):1765-9. doi: 10.1126/science.288.5472.1765.
Background: PubMed 11818772Rivat C, Laulin JP, Corcuff JB, Celerier E, Pain L, Simonnet G. Fentanyl enhancement of carrageenan-induced long-lasting hyperalgesia in rats: prevention by the N-methyl-D-aspartate receptor antagonist ketamine. Anesthesiology. 2002 Feb;96(2):381-91. doi: 10.1097/00000542-200202000-00025.
Background: PubMed 12544821Simonnet G, Rivat C. Opioid-induced hyperalgesia: abnormal or normal pain? Neuroreport. 2003 Jan 20;14(1):1-7. doi: 10.1097/00001756-200301200-00001. No abstract available.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Philippe RICHEBE, Dr study director

University Hospital, Bordeaux

Gérard JANVIER, PHD principal investigator

University Hospital, Bordeaux

Claude DUBRAY, PHD principal investigator

University Hospital, Bordeaux

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study of Pain, Postoperative, run by University Hospital, Bordeaux at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00454259, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.