Pharmacogenomics of Methadone in Spine Fusion Surgery
Information source: Northwestern University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Scoliosis; Kyphosis
Intervention: Methadone (Drug)
Phase: Phase 1
Status: Withdrawn
Sponsored by: Northwestern University Official(s) and/or principal investigator(s): Dhanesh K. Gupta, M.D., Principal Investigator, Affiliation: Northwestern University Feinberg School of Medicine
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.
Clinical Details
Official title: The Influence of Pharmacogenetics on Methadone Dose, Safety, and Outcomes After Spine Fusion
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Time until initial request for postoperative analgesic.
Secondary outcome: The determination of minimum effective analgesic concentration of methadone.Postoperative pain at rest and with movement (numerical rating scale, NRS) The number of occurrences of ventilatory depression during each evaluation interval Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis Level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale) Occurence of pruritis Algometry to assess pain tolerance Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS) Quality of Recovery: Quality of Recovery-40 score Patient analgesic satisfaction Assessment of back condition pre and post-operatively Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects Pupillometry for assessment of sedation
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
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
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
Locations and Contacts
Northwestern Memorial Hospital, Chicago, Illinois 60611, United States
Additional Information
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Starting date: March 2014
Last updated: April 21, 2015
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