Healthy Subjects Clinical Trial
— TMEOfficial title:
Effect of High-dose Target-controlled Naloxone Infusion on Pain and Hyperal-gesia in Patients Following Recovery From Impacted Mandibular Third Molar Extraction. A Randomized, Placebo-controlled, Double-blind Crossover Study.
Verified date | February 2024 |
Source | University of Copenhagen |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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, the 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. The investigators aim to show that latent sensitization is present in humans and is modulated by endogenous opioids.
Status | Completed |
Enrollment | 23 |
Est. completion date | December 27, 2023 |
Est. primary completion date | November 27, 2023 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 18 Years to 65 Years |
Eligibility | INCLUSION CRITERIA: - Healthy male - Age, minimum 18 yrs and maximum 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. - Standardized surgical procedure. - Urin-sample without traces of opioids (morphine, methadon, buprenorphine, codeine, tramadol, ketobemidone, oxycodone, hydromorphone, dextromethorphan) - ASA I-II - Body mass index (BMI): 18 < BMI < 30 kg/m2 EXCLUSION CRITERIA: - Participants, who do not speak or understand Danish - Participants, who cannot cooperate with the investigation - Participants, who have had previous surgery in the mandibular region - 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 - Skin lesions or tattoos in the assessment areas - 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 |
Country | Name | City | State |
---|---|---|---|
Denmark | Neuroscience Center, Copenhagen University Hospital | Copenhagen |
Lead Sponsor | Collaborator |
---|---|
mads u werner | University of Kentucky |
Denmark,
Brennum J, Kaiser F, Dahl JB. Effect of naloxone on primary and secondary hyperalgesia induced by the human burn injury model. Acta Anaesthesiol Scand. 2001 Sep;45(8):954-60. doi: 10.1034/j.1399-6576.2001.450806.x. — View Citation
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Pereira MP, Werner MU, Ringsted TK, Rowbotham MC, Taylor BK, Dahl JB. Does naloxone reinstate secondary hyperalgesia in humans after resolution of a burn injury? A placebo-controlled, double-blind, randomized, cross-over study. PLoS One. 2013 May 31;8(5): — View Citation
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* Note: There are 13 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in the composite measure of pain (numerical rating scale (NRS); 0 = no pain; 10 = worst perceivable pain) | during rest + masticatory pain + pain during external algometry (100 kPa) at the injury site | 1st session: 4 weeks after TME-surgery; 2nd session: 1 week later. At each session assessments are made at: -20 to -8 min; 15 to 25 min (TCI-step 1); 40 to 50 min (TCI-step 2); and 65 to 75 min (TCI-step 3) relative to start of TCI. | |
Secondary | Secondary hyperalgesia/allodynia area at mandibular skin sites directly overlying surgical and contralateral side | Hyperalgesia/allodynia assessments with nylon monofilament (nominal value 4.93 [bending force: mean +/- SD = 69 +/- 14 mN] | 1st session: 4 weeks after TME-surgery; 2nd session: 1 week later. At each session assessments are made at: -20 to -8 min; 15 to 25 min (TCI-step 1); 40 to 50 min (TCI-step 2); and 65 to 75 min (TCI-step 3) relative to start of TCI. | |
Secondary | Online Reaction Time | measured using http://getyourwebsiteherecom/jswb/rttest01.htm. This computer-application shows a red-green traffic light. Participants are instructed to press the button when the light changes from red to green. Three measurements are used and the median value is used as a representative estimate of reaction time. | 1st session: 4 weeks after TME-surgery; 2nd session: 1 week later. At each session assessments are made at: -20 to -8 min; 15 to 25 min (TCI-step 1); 40 to 50 min (TCI-step 2); and 65 to 75 min (TCI-step 3) relative to start of TCI. | |
Secondary | Hospital Anxiety and Depression Scale (HADS) | HADS is used to assess anxiety and signs of depression. Based on 14 questions about the subject's status in the previous week, HADS measures agitation/anxiety and depression via two subscales (each containing seven questions). Participants have to answer each question on a scale of 0 to 3. The two subscales are summed separately. The maximum score of each subscale is 21 points and a score of 11 or more points suggests that the participant might be suffering from anxiety or depression. In case of score > 11 points in the depression subscale of the HADS, a physician will decide if there are clinical signs of depression. If there are signs of depression, this diagnosis will be told to the participant. The participant will be informed that the diagnosis of depression is based on clinical assessments - the HADS scale can be included in the diagnostic procedure. If it is the participants wish, he should visit his general practitioner for diagnosis and eventual treatment. | 1st session: 4 weeks after TME-surgery; 2nd session: 1 week later. Only pre-infusion | |
Secondary | Pain Catastrophizing Scale (PCS) | PCS consists of 13 questions divided into three sections: rumination, exaggeration and helplessness. The questions are answered in accordance to a scale of 0 to 4. There is evidence of catastrophizing thoughts at a total score > 30 points. | 1st session: 4 weeks after TME-surgery; 2nd session: 1 week later. Only pre-infusion | |
Secondary | Clinical Opiate Withdrawal Scale (COWS) | The Clinical Opiate Withdrawal Scale (COWS) is an examiner-based scale evaluating signs of opioid-withdrawal. Grading of symptoms, i.e. heart rate changes, sweating, restlessness, pupil size, bone or joint aches, running nose or tearing, nausea, vomiting, diarrhea, tremor, yawning, anxiety or irritability and "goose-flesh", are made in 11 categories. COWS-scores are divided into: 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe ;> 36 = severe withdrawal reactions. | 1st session: 4 weeks after TME-surgery; 2nd session: 1 week later. At each session assessments are made at: -20 to -8 min; 15 to 25 min (TCI-step 1); 40 to 50 min (TCI-step 2); and 65 to 75 min (TCI-step 3) relative to start of TCI. |
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