- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01992146
Effect of High-dose Naloxone Infusion on Pain and Hyperalgesia in Patients Following Groin-Hernia Repair.
Effect of High-dose Naloxone Infusion on Pain and Hyperalgesia in Patients Following Groin-Hernia Repair. A Randomized, Placebo-controlled, Double-blind Crossover Study
Recent studies have focused on the role of endogenous opioids on central sensitization. Central sensitization is known to be impaired or altered in chronic pain conditions, as fibromyalgia or chronic tension headache.
Animal studies have shown reinstatement of mechanical hypersensitivity following naloxone administration after resolution of an injury. This suggests latent sensitization.
In the present study, investigators hypothesize that a high-dose target-controlled naloxone infusion (total dose: 3.25 mg/kg) can reinstate pain and hyperalgesia 6-8 weeks after a unilateral primary open groin hernia repair procedure. Investigators aim to show that latent sensitization is present in humans and is modulated by endogenous opioids.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Mads U Werner, M.D., D.M.Sc.
- Phone Number: +45 3545 7618
- Email: mads.u.werner@gmail.com
Study Contact Backup
- Name: Anne Willum, A.P.R.N
- Phone Number: +45 3545 7623
- Email: anne.willum@hotmail.com
Study Locations
-
-
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Copenhagen, Denmark, 2100
- Multidisciplinary Pain Center, 7612, HOC, Rigshospitalet
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age ≥ 18 years and ≤ 65 years
- Signed informed consent
- Patients submitted to unilateral, primary inguinal, open herniotomy 6-8 weeks prior to study start.
- Open operating procedure a.m. Lichtenstein.
- Urin sample without traces of opioids (morphine, methadon, buprenorphine, codeine, tramadol, ketobemidone, oxycodone, hydromorphine, dextromethorphan)
- ASA I-II
- Body mass index (BMI): 18 < BMI < 30
Exclusion Criteria:
- Volunteers , who do not speak or understand Danish
- Patients, who cannot cooperate with the investigation
- Patients who have had previous surgery in the groin region
- Patients with pain at rest > 3 (NRS)
- Activity-related pain in the surgical field > 5
- Allergic reaction against morphine or other opioids (including naloxone),
- Abuse of alcohol or drugs - according to investigator's evaluation
- Use of psychotropic drugs (exception of SSRI)
- Neurologic or psychiatric disease
- Chronic pain condition
- Regular use of analgesic drugs
- Skin lesions and tattoos in the assessment areas
- Nerve lesions in the assessment sites (for instance, after trauma, disc herniation, etc.)
- Use of prescription drugs 1 week before the trial
- Use of over-the-counter drugs 48 hours before the trial
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Change in Pain Ratings (NRS) at the surgical site and at the mirror-site in the contralateral groin six to eight weeks after unilateral herniotomy following administration of placebo.
|
|
Experimental: Target-controlled naloxone-infusion (total dose: 3.25 mg/kg)
Change in Pain Ratings (NRS) at the surgical site and at the mirror-site in the contralateral groin six to eight weeks after unilateral herniotomy following administration of naloxone.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Summated pain intensity
Time Frame: 1st session: 6-8 weeks after surgery; 2nd session: one week later
|
Change in pain ratings ([NRS,0-10] pain at rest + pain during transition from supine to standing position + pain during pressure (100 kPa) at injury site), assessed 6-8 weeks after unilateral, primary, open groin hernia repair following administration of naloxone/placebo.
|
1st session: 6-8 weeks after surgery; 2nd session: one week later
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Secondary hyperalgesia/allodynia
Time Frame: 1st session: 6-8 weeks after surgery; 2nd session: one week later
|
Change in secondary hyperalgesia area/allodynia at surgical site and at the mirror-site in the contralateral groin assessed 6-8 weeks after unilateral, primary, open groin hernia repair following administration of naloxone/placebo.
|
1st session: 6-8 weeks after surgery; 2nd session: one week later
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Pressure pain thresholds
Time Frame: 1st session: 6-8 weeks; 2nd session: one week later
|
Change in pressure pain thresholds at surgical site and at the mirror-site in the contralateral groin assessed 6-8 weeks after unilateral, primary, open groin hernia repair following administration of naloxone/placebo.
|
1st session: 6-8 weeks; 2nd session: one week later
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pain Catastrophizing Scale
Time Frame: in the 1st session: 6-8 weeks after surgery
|
Patients fill out Pain Catastrophizing Scale before assessments on the first study day
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in the 1st session: 6-8 weeks after surgery
|
Hospital Anxiety and Depression Scale
Time Frame: in the 1st session: 6-8 weeks after surgery
|
Patients fill out Hospital Anxiety and Depression Scale before assessments on the first study day
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in the 1st session: 6-8 weeks after surgery
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Clinical Opiate Withdrawal Scale
Time Frame: 1st session: 6-8 weeks after surgery; 2nd session: one week later
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Clinical Opiate Withdrawal Scale is filled out before and during naloxone/placebo administration in each experimental session
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1st session: 6-8 weeks after surgery; 2nd session: one week later
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mads U Werner, M.D., D.M.Sc., Rigshospitalet, Denmark
- Study Director: Mads U Werner, M.D., D.M.Sc., Rigshospitalet, Denmark
Publications and helpful links
General Publications
- Papathanasiou T, Springborg AD, Kongstad KT, Staerk D, Moller K, Taylor BK, Lund TM, Werner MU. High-dose naloxone, an experimental tool uncovering latent sensitisation: pharmacokinetics in humans. Br J Anaesth. 2019 Aug;123(2):e204-e214. doi: 10.1016/j.bja.2018.12.007. Epub 2019 Jan 18.
- Pereira MP, Werner MU, Dahl JB. Effect of a high-dose target-controlled naloxone infusion on pain and hyperalgesia in patients following groin hernia repair: study protocol for a randomized controlled trial. Trials. 2015 Nov 10;16:511. doi: 10.1186/s13063-015-1021-6. Erratum In: Trials. 2016;17:41. Pereira, Manuel Pedro; Utke Werner, Mads and Berg Dahl, Joergen [Corrected to Pereira, M P; Werner, M U and Dahl, J B].
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neurologic Manifestations
- Pathological Conditions, Anatomical
- Hernia, Abdominal
- Sensation Disorders
- Somatosensory Disorders
- Hernia
- Hernia, Inguinal
- Hyperalgesia
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Sensory System Agents
- Narcotic Antagonists
- Naloxone
Other Study ID Numbers
- MP_SM01_2013
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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