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

Primary Purpose

Central Nervous System Sensitization, Pain, Hyperalgesia

Status

Unknown status

Phase

Phase 2

Locations

Denmark

Study Type

Interventional

Intervention

Target-controlled naloxone-infusion

Placebo

About this trial

This is an interventional basic science trial for Central Nervous System Sensitization focused on measuring central sensitization, endogenous opioids, humans, latent sensitization, naloxone, open groin hernia repair, pain, randomized controlled trial, secondary hyperalgesia, target-controlled infusion

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Multidisciplinary Pain Center, 7612, HOC, RigshospitaletRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

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

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Secondary hyperalgesia/allodynia

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.

Pressure pain thresholds

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.

Full Information

NCT ID

NCT01992146

First Posted

November 7, 2013

Last Updated

November 23, 2015

Sponsor

Rigshospitalet, Denmark

Collaborators

University of Kentucky, National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT01992146

Brief Title

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

Official Title

Effect of High-dose Naloxone Infusion on Pain and Hyperalgesia in Patients Following Groin-Hernia Repair. A Randomized, Placebo-controlled, Double-blind Crossover Study

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Unknown status

Study Start Date

November 2015 (undefined)

Primary Completion Date

July 2016 (Anticipated)

Study Completion Date

December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Rigshospitalet, Denmark

Collaborators

University of Kentucky, National Institute on Drug Abuse (NIDA)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

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

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Target-controlled naloxone-infusion

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Summated pain intensity

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Secondary hyperalgesia/allodynia

Description

Time Frame

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

Title

Pressure pain thresholds

Description

Time Frame

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

Other Pre-specified Outcome Measures:

Title

Pain Catastrophizing Scale

Description

Patients fill out Pain Catastrophizing Scale before assessments on the first study day

Time Frame

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

Title

Hospital Anxiety and Depression Scale

Description

Patients fill out Hospital Anxiety and Depression Scale before assessments on the first study day

Time Frame

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

Title

Clinical Opiate Withdrawal Scale

Description

Clinical Opiate Withdrawal Scale is filled out before and during naloxone/placebo administration in each experimental session

Time Frame

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

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mads U Werner, M.D., D.M.Sc.

Phone

+45 3545 7618

mads.u.werner@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Anne Willum, A.P.R.N

Phone

+45 3545 7623

anne.willum@hotmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mads U Werner, M.D., D.M.Sc.

Organizational Affiliation

Rigshospitalet, Denmark

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Mads U Werner, M.D., D.M.Sc.

Organizational Affiliation

Rigshospitalet, Denmark

Official's Role

Study Director

Facility Information:

Facility Name

Multidisciplinary Pain Center, 7612, HOC, Rigshospitalet

City

Copenhagen

ZIP/Postal Code

2100

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mads U Werner, M.D., D.M.Sc

Phone

+45 3545 7618

mads.u.werner@gmail.com

First Name & Middle Initial & Last Name & Degree

Anne Willum, A.P.R.N

Phone

+45 3545 7623

anne.willum@hotmail.com

First Name & Middle Initial & Last Name & Degree

Anne Willum, R.N.

First Name & Middle Initial & Last Name & Degree

Anders Springborg, M.S.

12. IPD Sharing Statement

Citations:

PubMed Identifier

30915992

Citation

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.

Results Reference

derived

PubMed Identifier

26554360

Citation

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].

Results Reference

derived

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

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