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Pharmacogenomics of Methadone in Spine Fusion Surgery

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ClinicalTrials.gov Identifier: NCT01677650
Recruitment Status : Withdrawn (Investigator moved to new institution)
First Posted : September 3, 2012
Last Update Posted : April 22, 2015
Sponsor:
Information provided by (Responsible Party):
Dhanesh Gupta, Northwestern University

Tracking Information
First Submitted Date  ICMJE August 30, 2012
First Posted Date  ICMJE September 3, 2012
Last Update Posted Date April 22, 2015
Study Start Date  ICMJE March 2014
Estimated Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2012)
Time until initial request for postoperative analgesic. [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2012)
  • 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 Measures  ICMJE
 (submitted: August 31, 2012)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacogenomics of Methadone in Spine Fusion Surgery
Official Title  ICMJE 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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Scoliosis
  • Kyphosis
Intervention  ICMJE Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Other Name: Dolophine
Study Arms  ICMJE
  • Active Comparator: Methadone 0.5 mg/kg
    Methadone 0.5 mg/kg
    Intervention: Drug: Methadone
  • Experimental: Methadone 0.4 mg/kg
    Methadone 0.4 mg/kg
    Intervention: Drug: Methadone
  • Active Comparator: Methadone 0.3 mg/kg
    Methadone 0.3 mg/kg
    Intervention: Drug: Methadone
  • Active Comparator: Methadone 0.2 mg/kg
    Methadone 0.2 mg/kg
    Intervention: Drug: Methadone
  • Active Comparator: Methadone 0.15 mg/kg
    Methadone 0.15 mg/kg
    Intervention: Drug: Methadone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: April 21, 2015)
0
Original Estimated Enrollment  ICMJE
 (submitted: August 31, 2012)
95
Estimated Study Completion Date  ICMJE January 2015
Estimated Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01677650
Other Study ID Numbers  ICMJE STU00064915
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dhanesh Gupta, Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dhanesh K. Gupta, M.D. Northwestern University Feinberg School of Medicine
PRS Account Northwestern University
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP