Clinical Trial: Pharmacogenomics of Methadone in Spine Fusion Surgery

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: The Influence of Pharmacogenetics on Methadone Dose, Safety, and Outcomes After Spine Fusion

Brief Summary: The overall objective is to develop a patient oriented research program to efficiently evaluate the effects of pharmacogenetic variants on the dose-response relationships and safety of opioids and non-opioid analgesics. If an opioid regimen can be created that produces excellent opioid analgesia with minimal toxicity related to supratherapeutic opioid concentrations (i.e., ventilatory depression), other non-opioid analgesics (i.e., gabapentin/pregabalin, ketamine, lidocaine, cyclooxygenase inhibitors, etc.) that may decrease preoperative opioid requirements can be more efficiently and safely evaluated. These interventions may limit the opioid related toxicities related to effect site concentrations that are below those required when opioids are the predominant analgesic, such as opioid related ileus. Methadone's slow elimination clearance and limited pharmacokinetic drug-drug interactions make it an attractive perioperative opioid. The first step towards personalized opioid analgesia is to determine the effect of common pharmacogenetic variants that affect either methadone metabolism (CYP2B6) or opioid elimination.

Detailed Summary: This study is being done to find the optimal dose of methadone (a long acting pain medication) that decreases the amount of pain that people have after spine surgery. Five different doses of methadone will be compared to each other, while keeping the remainder of the anesthetic routine for surgery. The investigators will determine the analgesic dose-response of methadone. The investigators will also determine the effect of methadone on the incidence of opioid related side effects, the quality of outcome of recovery, and the change in the 3-month opioid use.
Sponsor: Northwestern University

Current Primary Outcome: Time until initial request for postoperative analgesic. [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The determination of minimum effective analgesic concentration of methadone. [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Postoperative pain at rest and with movement (numerical rating scale, NRS) [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • The number of occurrences of ventilatory depression during each evaluation interval [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale) [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Occurence of pruritis [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Algometry to assess pain tolerance [ Time Frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS) [ Time Frame: 24, 48, and 72 hours after methadone administration ]
  • Quality of Recovery: Quality of Recovery-40 score [ Time Frame: 24, 48, and 72 hours after methadone administration ]
  • Patient analgesic satisfaction [ Time Frame: 24, 48, and 72 hours after methadone administration ]
  • Assessment of back condition pre and post-operatively [ Time Frame: Pre-operatively, 6 weeks and 3 months post-operatively ]
  • Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects [ Time Frame: Preoperatively ]

    CYP2B6 Polymorphism effect on

    1. Time to first request for analgesia
    2. Secondary outcomes
  • Pupillometry for assessment of sedation [ Time Frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]


Original Secondary Outcome:

  • The determination of minimum effective analgesic concentration of methadone. [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Postoperative pain at rest and with movement (numerical rading scale, NRS) [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • The number of occurrences of ventilatory depression during each evaluation interval [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale) [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Occurence of pruritis [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Algometry to assess pain tolerance [ Time Frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
  • Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS) [ Time Frame: 24, 48, and 72 hours after methadone administration ]
  • Quality of Recovery: Quality of Recovery-40 score [ Time Frame: 24, 48, and 72 hours after methadone administration ]
  • Patient analgesic satisfaction [ Time Frame: 24, 48, and 72 hours after methadone administration ]
  • Assessment of back condition pre and post-operatively [ Time Frame: Pre-operatively, 6 weeks and 3 months post-operatively ]
  • Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects [ Time Frame: Preoperatively ]
    From preoperative baseline blood sample
  • Pupillometry for assessment of sedation [ Time Frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]


Information By: Northwestern University

Dates:
Date Received: August 30, 2012
Date Started: March 2014
Date Completion: January 2015
Last Updated: April 21, 2015
Last Verified: April 2015