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

NCT01992146 | Completed Phase 2 DMC

• 1 other identifier: MP_SM01_2013
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Central Nervous System Sensitization; Pain; Hyperalgesia

Keywords

central sensitization; endogenous opioids; humans; latent sensitization; naloxone; open groin hernia repair; pain; randomized controlled trial; secondary hyperalgesia; target-controlled infusion

Outcome Measures

Primary Outcomes (1)

• Summated pain intensity

  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 Outcomes (2)

• Secondary hyperalgesia/allodynia

  1st session: 6-8 weeks after surgery; 2nd session: one week later

• Pressure pain thresholds

  1st session: 6-8 weeks; 2nd session: one week later

Other Outcomes (3)

• Pain Catastrophizing Scale

  in the 1st session: 6-8 weeks after surgery

• Hospital Anxiety and Depression Scale

  in the 1st session: 6-8 weeks after surgery

• Clinical Opiate Withdrawal Scale

  1st session: 6-8 weeks after surgery; 2nd session: one week later

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Target-controlled naloxone-infusion (total dose: 3.25 mg/kg)

EXPERIMENTAL

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.

Drug: Target-controlled naloxone-infusion

Interventions

Target-controlled naloxone-infusion DRUG

Target-controlled naloxone-infusion (total dose: 3.25 mg/kg)

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• University of Kentucky: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Multidisciplinary Pain Center, 7612, HOC, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (2)

• 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.

  PMID: 30915992 DERIVED

• 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.

  PMID: 26554360 DERIVED

MeSH Terms

Conditions

Pain; Hyperalgesia

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Nervous System Diseases

Study Officials

• Mads U Werner, M.D., D.M.Sc.

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Mads U Werner, M.D., D.M.Sc.

  Rigshospitalet, Denmark

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: November 7, 2013
• First Posted: November 25, 2013
• Study Start: November 11, 2015
• Primary Completion: December 14, 2015
• Study Completion: May 11, 2018
• Last Updated: February 22, 2024

Record last verified: 2024-02

Locations

DK (1)