Effect of high-dose naloxone - an antidote to morphine - on pain sensitivity after removal of a wisdom tooth.

"Effect of High-dose Target-controlled Naloxone Infusion on Pain and Hyperalgesia in Patients following Recovery from Impacted Mandibular Third Molar Extraction. A Randomized, Placebo-controlled, Double-blind Crossover Study." - HighNxTME

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-005426-19-DK

Enrollment

Registered

2015-12-10

Start date

2016-02-09

Completion date

Unknown

Last updated

2024-02-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy volunteers (n = 94) are included. The main study includes 14 subjects who have had an uncomplicated, impacted mandibular, third molar extraction 4-5 weeks prior to participation in the study. The sub-study includes 80 subjects who will receive a first degree heat injury. MedDRA version: 18.1 Level: LLT Classification code 10049475 Term: Chronic pain System Organ Class: 100000004867

Interventions

Trade Name: Naloxon "B. Braun" Product Name: Not applicable Product Code: Not applicable Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: NALOXONE CAS Number: 465-65-6 Concent

Eligibility

Sex/Gender

Male

Inclusion criteria

Inclusion criteria: • Healthy male • Age above 18 yrs and below 65 yrs • Signed informed consent • Participants submitted to unilateral, primary, impacted, uncomplicated mandibular third molar extraction 4 weeks (+ 3 days) prior to examination Day 1 (main study). • Standardized surgical procedure (main study). • Urin-sample without traces of opioids (morphine, methadon, buprenorphine, codeine, tramadol, ketobemidone, oxycodone, hydromorphone, dextromethorphan) • ASA I-II • Body mass index (BMI): 18 =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: • Participants, who cannot cooperate with the investigation • Participants, who have had previous surgery in the mandibular region (main study) • Participants with pain at rest > 3 (NRS [0: no pain; 10: worst perceivable pain]) • Activity-related pain in the surgical field > 5 (NRS) • 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 • Nerve lesions in the assessment sites (e.g., after trauma, dental surgery) • Use of prescription drugs one week before the trial • Use of over-the-counter (OTC) drugs 48 hours before the trial • Scarring or tattoos in the examination areas

Design outcomes

Primary

Measure	Time frame
Main Objective: The principal aim of the study is to investigate whether the administration of naloxone, a selective mu-opioid receptor (MOR) antagonist, can re-introduce pain (at rest, during mastication and during pressure-evoked condition) and hyperalgesia four to five weeks after unilateral, uncomplicated, impacted mandibular, third molar extraction (TME; n = 14). A three-step the target-controlled-infusion (TCI) model is employed.;Secondary Objective: Secondary objectives are assessments of: oSecondary hyperalgesia/allodynia area assessed by a polyamide monofilament at mandibular skin sites directly overlying surgical and contralateral side oOnline Reaction Time oHospital Anxiety and Depression Scale (HADS; only pre-infusion) oPain Catastrophizing Scale (PCS; only pre-infusion) oClinical Opiate Withdrawal Scale ;Primary end point(s): (Abbreviations: BL = baseline; NX = naloxone; NRS = numerical rating scale; PL = placebo; TCI = during target-controlled-infusion): 1.a primary outcome based on a summed measure (SM) of resting pain (RP), masticatory pain (MP; (movement-related) and pressure-evoked pain (PM; pressure algometry [100 kPa]). NRS-SM = NRS-RP + NRS-MP + NRS-PM. 2.the summed pain intensities (SPIs) are calculated as: (BL-SPINX) and (TCI-SPINX), and, (BL-SPIPL) and (TCI-SPIPL), where (TCI-SPI) indicates SM-value at highest obtainable TCI-step (Fig. 2). 3.the summed pain intensity differences (SPIDs) are the differences: SPIDNX = (TCI-SPINX) – (BL-SPINX) and SPIDPL = (TCI-SPIPL) - (BL-SPIPL) 4. the primary endpoint is: ?SPID = SPIDNX - SPIDPL (MIREDIF = 45%) For the sub-study: 1. secondary hyperalgesia areas (SHAs) are measured at BL and during highest obtainable TCI-level 2. Differences are calculated: (TCI-SHANX – BL-SHANX) and (TCI-SHAPL - BLSHAPL) 3. the primary endpoint is: ? SHA = (TCI-SHANX – BL-SHANX) - (TCI-SHAPL - BLSHAPL). MIREDIF is not possible to calculate due to the exploratory nature of the sub-study. ;Timepoint(s) of evaluation	—

Measure

Time frame

Main Objective: The principal aim of the study is to investigate whether the administration of naloxone, a selective mu-opioid receptor (MOR) antagonist, can re-introduce pain (at rest, during mastication and during pressure-evoked condition) and hyperalgesia four to five weeks after unilateral, uncomplicated, impacted mandibular, third molar extraction (TME; n = 14). A three-step the target-controlled-infusion (TCI) model is employed.;Secondary Objective: Secondary objectives are assessments of: oSecondary hyperalgesia/allodynia area assessed by a polyamide monofilament at mandibular skin sites directly overlying surgical and contralateral side oOnline Reaction Time oHospital Anxiety and Depression Scale (HADS; only pre-infusion) oPain Catastrophizing Scale (PCS; only pre-infusion) oClinical Opiate Withdrawal Scale ;Primary end point(s): (Abbreviations: BL = baseline; NX = naloxone; NRS = numerical rating scale; PL = placebo; TCI = during target-controlled-infusion): 1.a primary outcome based on a summed measure (SM) of resting pain (RP), masticatory pain (MP; (movement-related) and pressure-evoked pain (PM; pressure algometry [100 kPa]). NRS-SM = NRS-RP + NRS-MP + NRS-PM. 2.the summed pain intensities (SPIs) are calculated as: (BL-SPINX) and (TCI-SPINX), and, (BL-SPIPL) and (TCI-SPIPL), where (TCI-SPI) indicates SM-value at highest obtainable TCI-step (Fig. 2). 3.the summed pain intensity differences (SPIDs) are the differences: SPIDNX = (TCI-SPINX) – (BL-SPINX) and SPIDPL = (TCI-SPIPL) - (BL-SPIPL) 4. the primary endpoint is: ?SPID = SPIDNX - SPIDPL (MIREDIF = 45%) For the sub-study: 1. secondary hyperalgesia areas (SHAs) are measured at BL and during highest obtainable TCI-level 2. Differences are calculated: (TCI-SHANX – BL-SHANX) and (TCI-SHAPL - BLSHAPL) 3. the primary endpoint is: ? SHA = (TCI-SHANX – BL-SHANX) - (TCI-SHAPL - BLSHAPL). MIREDIF is not possible to calculate due to the exploratory nature of the sub-study. ;Timepoint(s) of evaluation

—

Secondary

Measure	Time frame
Secondary end point(s): * Pressure pain thresholds (PPT) and secondary hyperalgesia/allodynia areas are assessed at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion1: 15 to 25 min); Step 2 (TCI-infusion 2: 39 to 49 min); Step 3 (TCI-infusion 3: 65 to 75 min). * Clinical Opiate Withdrawal Scale (COWS) and Online Reaction Time assessments are made at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion 1: 13 to 15 min); Step 2 (TCI-infusion 2: 37 to 39 min); Step 3 (TCI-infusion 3: 63 to 65 min). * Psychometrics (Hospital Anxiety and Depression Scale [HADS], Pain Catastrophizing Scale [PCS]) are only assessed at Baseline (pre-infusion; 0 min). For the sub-study: * Pain during FTI (NRS; 0,1,2,3,4,5,6 and 7 min after thermal injury). * Pin-prick pain thresholds (PPT) assessed by weighted-pin instruments at primary and secondary hyperalgesia areas (0, 1, 2, 165 and 165-169 hrs (during TCI [time; 15 to 25 min; 44 to 4 min'; and 70 to 75 min]) after TFI. * Clinical Opiate Withdrawal Scale (COWS) and Online Reaction Time assessments are made at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion 1: 13 to 15 min); Step 2 (TCI-infusion 2: 37 to 39 min); Step 3 (TCI-infusion 3: 63 to 65 min). * Hospital Anxiety and Depression Scale (HADS; only pre-FTI) * Pain Catastrophizing Scale (PCS; only pre-FTI);Timepoint(s) of evaluation of this end point: * Pressure pain thresholds (PPT) and secondary hyperalgesia/allodynia areas are assessed at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion1: 15 to 25 min); Step 2 (TCI-infusion 2: 39 to 49 min); Step 3 (TCI-infusion 3: 65 to 75 min). * Clinical Opiate Withdrawal Scale (COWS) and Online Reaction Time assessments are made at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion 1: 13 to 15 min); Step 2 (TCI-infusion 2: 37 to 39 min); Step 3 (TCI-infusion 3: 63 to 65 min). * Psychometrics (Hospital Anxiety and Depression Scale [HADS], Pain Catastrophizing Scale [PCS]) are only assessed at Baseline (pre-infusion; 0 min).	—

Measure

Time frame

Secondary end point(s): * Pressure pain thresholds (PPT) and secondary hyperalgesia/allodynia areas are assessed at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion1: 15 to 25 min); Step 2 (TCI-infusion 2: 39 to 49 min); Step 3 (TCI-infusion 3: 65 to 75 min). * Clinical Opiate Withdrawal Scale (COWS) and Online Reaction Time assessments are made at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion 1: 13 to 15 min); Step 2 (TCI-infusion 2: 37 to 39 min); Step 3 (TCI-infusion 3: 63 to 65 min). * Psychometrics (Hospital Anxiety and Depression Scale [HADS], Pain Catastrophizing Scale [PCS]) are only assessed at Baseline (pre-infusion; 0 min). For the sub-study: * Pain during FTI (NRS; 0,1,2,3,4,5,6 and 7 min after thermal injury). * Pin-prick pain thresholds (PPT) assessed by weighted-pin instruments at primary and secondary hyperalgesia areas (0, 1, 2, 165 and 165-169 hrs (during TCI [time; 15 to 25 min; 44 to 4 min'; and 70 to 75 min]) after TFI. * Clinical Opiate Withdrawal Scale (COWS) and Online Reaction Time assessments are made at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion 1: 13 to 15 min); Step 2 (TCI-infusion 2: 37 to 39 min); Step 3 (TCI-infusion 3: 63 to 65 min). * Hospital Anxiety and Depression Scale (HADS; only pre-FTI) * Pain Catastrophizing Scale (PCS; only pre-FTI);Timepoint(s) of evaluation of this end point: * Pressure pain thresholds (PPT) and secondary hyperalgesia/allodynia areas are assessed at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion1: 15 to 25 min); Step 2 (TCI-infusion 2: 39 to 49 min); Step 3 (TCI-infusion 3: 65 to 75 min). * Clinical Opiate Withdrawal Scale (COWS) and Online Reaction Time assessments are made at Baseline (pre-infusion; 0 min); Step 1 (TCI-infusion 1: 13 to 15 min); Step 2 (TCI-infusion 2: 37 to 39 min); Step 3 (TCI-infusion 3: 63 to 65 min). * Psychometrics (Hospital Anxiety and Depression Scale [HADS], Pain Catastrophizing Scale [PCS]) are only assessed at Baseline (pre-infusion; 0 min).

—

Countries

Denmark

Contacts

Public ContactMultidisciplinary Pain Center 7612,

Rigshospitalet, Copenhagen University Hospitals

anne.willum@regionh.dk+4535457618

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026