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.
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
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
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
- 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 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.
- 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)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- University of Kentucky, National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Mads Werner, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Mads U Werner, M.D., D.M.Sc., Principal investigator, Copenhagen University Hospital, RigshospitaletMads U Werner, M.D., D.M.Sc., Study director, Copenhagen University Hospital, Rigshospitalet
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 30915992Pereira 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
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.
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 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.