Effect of High-dose Naloxone Infusion on Pain and Hyperalgesia in Patients Following Groin-Hernia Repair.

February 21, 2024 updated by: Mads Werner, Rigshospitalet, Denmark

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

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

      • Copenhagen, Denmark, 2100
        • Multidisciplinary Pain Center, 7612, HOC, Rigshospitalet

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

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: 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
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
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
in the 1st session: 6-8 weeks after surgery
Clinical Opiate Withdrawal Scale
Time Frame: 1st session: 6-8 weeks after surgery; 2nd session: one week later
Clinical Opiate Withdrawal Scale is filled out before and during naloxone/placebo administration in each experimental session
1st session: 6-8 weeks after surgery; 2nd session: one week later

Collaborators and Investigators

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

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

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

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 (Actual)

November 11, 2015

Primary Completion (Actual)

December 14, 2015

Study Completion (Actual)

May 11, 2018

Study Registration Dates

First Submitted

November 7, 2013

First Submitted That Met QC Criteria

November 18, 2013

First Posted (Estimated)

November 25, 2013

Study Record Updates

Last Update Posted (Estimated)

February 22, 2024

Last Update Submitted That Met QC Criteria

February 21, 2024

Last Verified

February 1, 2024

More Information

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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