Central Nervous System SensitizationPhase 2NCT01992146

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

A Phase 2 study of Central Nervous System Sensitization and Pain, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years, men only
Conditions the study is for: Central Nervous System Sensitization, Pain, Hyperalgesia
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 9 participants
Where: 1 siteDenmark
Study dates: 11 Nov 2015to 11 May 2018
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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),

Show all 15Show fewer

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

Trial locations and contacts

1 site in 1 country.

Denmark1 site

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

Other trials in Denmark

About this study

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

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
Being tested: Target-controlled naloxone-infusion, Placebo
Keywords: central sensitization, endogenous opioids, humans, latent sensitization, naloxone, open groin hernia repair, pain, randomized controlled trial, secondary hyperalgesia, target-controlled infusion
Medical subject headings: Pain, Hyperalgesia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Target-controlled naloxone-infusionDrug
PlaceboDrug

Study groups in NCT01992146
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Target-controlled naloxone-infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (2)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Nov 201511 May 2018

First posted25 Nov 2013 (estimated)
Study start11 Nov 2015
Primary completion14 Dec 2015
Study completion11 May 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Central Nervous System SensitizationStudies of the same condition, open and under way.
More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 9 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01992146
Sponsor's protocol ID: MP_SM01_2013
Status last verified: Feb 2024
First submitted: 7 Nov 2013
Last updated: 22 Feb 2024
Results posted: No
Data monitoring committee: Yes

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.
PubMed 30915992
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.
PubMed 26554360

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01992146
Acronym / sponsor ID: MP_SM01_2013
Conditions: Central Nervous System Sensitization, Pain, Hyperalgesia
Keywords: central sensitization, endogenous opioids, humans, latent sensitization, naloxone, open groin hernia repair, pain, randomized controlled trial
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 9 participants (actual)
Lead sponsor: Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
Collaborators: University of Kentucky, National Institute on Drug Abuse (NIDA)
Study start: 11 Nov 2015 (actual)
Primary completion: 14 Dec 2015 (actual)
Study completion: 11 May 2018 (actual)
First posted: 25 Nov 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Animal studies have shown reinstatement of mechanical hypersensitivity following naloxone administration after resolution of an injury. This suggests latent sensitization.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboChange 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.
Target-controlled naloxone-infusion (total dose: 3.25 mg/kg)	Experimental	Drug: Target-controlled naloxone-infusionChange 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.

Who may qualify

Ages: 18 to 65 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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)

Key exclusion criteria (15 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Target-controlled naloxone-infusion	Drug	Target-controlled naloxone-infusion (total dose: 3.25 mg/kg)
Placebo	Drug	Placebo

Primary outcome

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.

2 secondary outcomes

Secondary hyperalgesia/allodynia
Time frame: 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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2024.
Derived from this study: PubMed 30915992Papathanasiou 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.
Derived from this study: PubMed 26554360Pereira 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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

Copenhagen University Hospital, Rigshospitalet

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

Copenhagen University Hospital, Rigshospitalet

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study of Central Nervous System Sensitization and Pain, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Summated pain intensity (time frame: 1st session: 6-8 weeks after surgery; 2nd session: one week later). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01992146, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024.