Clinical trial NCT01677650: Pharmacogenomics of Methadone in Spine Fusion Surgery
Official title: The Influence of Pharmacogenetics on Methadone Dose, Safety, and Outcomes After Spine Fusion
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Scoliosis
Kyphosis
Keywords: Spinal Fusion
Opioid Analgesia
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2012-09-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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.

Eligibility criteria: Inclusion Criteria:

* ASA physical status I, II, and III
* male and non-pregnant female
* English-speaking
* undergoing elective \< 3 vertebral level lumbar spine fusion (with and without interbody fusion)

Exclusion Criteria:

* Use of more than the equivalent of 20 mg of IV morphine/24 hr in the past 2 weeks
* history of substance abuse at any time in the past
* known QT prolongation
* Non-elective operations (i.e., cancer or trauma)
* severe hepatic impairment (serum albumin \<3.0 g/dL, history of liver disease)
* pregnancy

Primary outcomes:
measure: Time until initial request for postoperative analgesic.
timeFrame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Secondary outcomes:
measure: The determination of minimum effective analgesic concentration of methadone.
timeFrame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Postoperative pain at rest and with movement (numerical rating scale, NRS)
timeFrame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: The number of occurrences of ventilatory depression during each evaluation interval
timeFrame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis
timeFrame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale)
timeFrame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Occurence of pruritis
timeFrame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Algometry to assess pain tolerance
timeFrame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
measure: Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS)
timeFrame: 24, 48, and 72 hours after methadone administration
measure: Quality of Recovery: Quality of Recovery-40 score
timeFrame: 24, 48, and 72 hours after methadone administration
measure: Patient analgesic satisfaction
timeFrame: 24, 48, and 72 hours after methadone administration
measure: Assessment of back condition pre and post-operatively
timeFrame: Pre-operatively, 6 weeks and 3 months post-operatively
measure: Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects
timeFrame: Preoperatively
measure: Pupillometry for assessment of sedation
timeFrame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
affiliation: Northwestern University Feinberg School of Medicine
name: Dhanesh K. Gupta, M.D.
role: PRINCIPAL_INVESTIGATOR
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