Comparison of A Single Dose Combination of Methadone and Morphine With Morphine Alone for Treating Post-operative Pain

Study Overview
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Brief Summary
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This is a randomized Phase II study testing the effectiveness of the combination of morphine and methadone versus morphine alone in relieving pain. A second goal is to further evaluate any side effects of the combination of morphine and methadone.

Detailed Description
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Rationale: Experimental data demonstrates a profound analgesic synergy between morphine and methadone when co-administered systemically in mice. If this type of synergy can be demonstrated in clinical pain, it will be a relatively unique example of translating concepts of fundamental aspects of opioid actions seen in the laboratory to the clinical area, and provide a basis for offering new and scientifically- based analgesic regimens. This may provide better pain relief with less opioid related side effects in clinical practice. Purpose: This is a randomized, double blind, parallel arm Phase II study comparing a single dose of 1:1 combination of methadone and morphine with morphine alone in patients with post-operative pain. The primary objective of this randomized, double blind, parallel arm Phase II study is to compare the analgesic effects of a combination of morphine and methadone with morphine alone to determine synergistic activity of mu opioid analgesics in patients with post-operative pain. A second goal is to further evaluate any side effects of the combination of morphine and methadone.

Official Title
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Translational Studies in Analgesic Pharmacology: Analgesic Synergy in Clinical Pain. A Phase 2 Study Comparing a Single Dose of a 1:1 Combination of Methadone and Morphine With Morphine Alone in Patients With Post-operative Pain.

Conditions
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Pain

Intervention / Treatment
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* Drug: Methadone
* Drug: methadone and morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Retroperitoneal lymph node dissection Planned post-operative analgesia with PCA at 1 mg continuous infusion and 1 mg every 10 minutes 18 years of age or older English-speaking Give informed consent to participate in this study Exclusion Criteria: Known hypersensitivity to methadone or morphine Patients with past or present history of substance abuse Patients with a history of methadone treatment Patients with a history of chronic pain requiring daily analgesic use for more than 3 months Patients treated with opioids within one month from the scheduled surgery Creatinine clearance less than 50 mg/kg (using Cockcroft-Gault Equation). Neurologic or psychiatric disease sufficient, in the doctor's opinion, to compromise data collection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>methadone | Drug: Methadone<br>* Upon the 1st request for analgesic medication morphine 2 mg, upon the 2nd request for analgesic medication morphine 2 mg<br>|
| Experimental: 2<br>methadone and morphine | Drug: methadone and morphine<br>* Upon the 1st request for analgesic medication morphine 2 mg, upon the 2nd request for analgesic medication morphine 1 mg and methadone 1 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Goal of This Study is to Compare the Analgesic Effects of a Combination of Morphine and Methadone With Morphine Alone to Determine Synergistic Activity of mu Opioid Analgesics in Patients With Post-operative Pain. |  | Time to the third request for the pain medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine if There Are Any Side Effects From the Combination of Morphine and Methadone When Given Together. |  | assessed every 10 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Analgesics, Retroperitoneal lymph node dissection