Fentanyl Ultra Low Doses Effects on the Nociceptive Threshold (FENTANULD)
Primary Purpose
Pain, Postoperative
Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Fentanyl/Placebo injection
Sponsored by
About this trial
This is an interventional health services research trial for Pain, Postoperative focused on measuring Postoperative Hyperalgesia, Human volunteer, Fentanyl, Randomized Controlled Trial, Pain chronicisation, Predictive test
Eligibility 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
Sites / Locations
- CHU de Bordeaux Département d'Anesthésie-Réanimation II
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
1
2
3
4
Arm Description
0,5 µg/kg
0,05 µg/kg
0,005 µg/kg
NaCl 0,9 %
Outcomes
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.
Secondary Outcome Measures
Non invasive blood pressure (SBP, DBP), heart rate, respiratory rate, pulse oxymetry and cognitive functions evaluation (sedation score).
Full Information
NCT ID
NCT00454259
First Posted
March 29, 2007
Last Updated
June 2, 2015
Sponsor
University Hospital, Bordeaux
1. Study Identification
Unique Protocol Identification Number
NCT00454259
Brief Title
Fentanyl Ultra Low Doses Effects on the Nociceptive Threshold
Acronym
FENTANULD
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?
Study Type
Interventional
2. Study Status
Record Verification Date
March 2007
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
August 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
University Hospital, Bordeaux
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative
Keywords
Postoperative Hyperalgesia, Human volunteer, Fentanyl, Randomized Controlled Trial, Pain chronicisation, Predictive test
7. Study Design
Primary Purpose
Health Services Research
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
0,5 µg/kg
Arm Title
2
Arm Type
Experimental
Arm Description
0,05 µg/kg
Arm Title
3
Arm Type
Experimental
Arm Description
0,005 µg/kg
Arm Title
4
Arm Type
Placebo Comparator
Arm Description
NaCl 0,9 %
Intervention Type
Drug
Intervention Name(s)
Fentanyl/Placebo injection
Intervention Description
Ultra low dose intravenous injection
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Non invasive blood pressure (SBP, DBP), heart rate, respiratory rate, pulse oxymetry and cognitive functions evaluation (sedation score).
Time Frame
all along the experimentation
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe RICHEBE, Dr
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Gérard JANVIER, PHD
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Claude DUBRAY, PHD
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alain ESCHALIER, PHD
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
jean DUALE CHRISTIAN, Dr
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gisèle PICKERING, Dr
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Bordeaux Département d'Anesthésie-Réanimation II
City
PESSAC Cedex
State/Province
Hôpital cardiologique
ZIP/Postal Code
33604
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
16129988
Citation
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.
Results Reference
background
PubMed Identifier
14527702
Citation
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.
Results Reference
background
PubMed Identifier
11020770
Citation
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.
Results Reference
background
PubMed Identifier
16698416
Citation
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.
Results Reference
background
PubMed Identifier
11356895
Citation
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.
Results Reference
background
PubMed Identifier
7681556
Citation
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.
Results Reference
background
PubMed Identifier
1981160
Citation
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.
Results Reference
background
PubMed Identifier
9786023
Citation
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.
Results Reference
background
PubMed Identifier
15681961
Citation
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.
Results Reference
background
PubMed Identifier
10846153
Citation
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.
Results Reference
background
PubMed Identifier
11818772
Citation
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.
Results Reference
background
PubMed Identifier
12544821
Citation
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.
Results Reference
background
Learn more about this trial
Fentanyl Ultra Low Doses Effects on the Nociceptive Threshold
We'll reach out to this number within 24 hrs