Pharmacogenomics of Methadone in Spine Fusion Surgery

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Dhanesh Gupta, Northwestern University
ClinicalTrials.gov Identifier:
NCT01677650
First received: August 30, 2012
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

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.

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.


Condition Intervention Phase
Spinal Fusion
Drug: Methadone
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Influence of Pharmacogenetics on Methadone Dose, Safety, and Outcomes After Spine Fusion

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Time until initial request for postoperative analgesic. [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The determination of minimum effective analgesic concentration of methadone. [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Occurence of pruritis [ Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ] [ Designated as safety issue: No ]
  • Algometry to assess pain tolerance [ Time Frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Quality of Recovery: Quality of Recovery-40 score [ Time Frame: 24, 48, and 72 hours after methadone administration ] [ Designated as safety issue: No ]
  • Patient analgesic satisfaction [ Time Frame: 24, 48, and 72 hours after methadone administration ] [ Designated as safety issue: No ]
  • Assessment of back condition pre and post-operatively [ Time Frame: Pre-operatively, 6 weeks and 3 months post-operatively ] [ Designated as safety issue: No ]
  • Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects [ Time Frame: Preoperatively ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 95
Study Start Date: March 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Methadone 0.5 mg/kg
Methadone 0.5 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Experimental: Methadone 0.4 mg/kg
Methadone 0.4 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Active Comparator: Methadone 0.3 mg/kg
Methadone 0.3 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Active Comparator: Methadone 0.2 mg/kg
Methadone 0.2 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Active Comparator: Methadone 0.15 mg/kg
Methadone 0.15 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01677650

Locations
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Dhanesh K. Gupta, M.D. Northwestern University Feinberg School of Medicine
  More Information

Publications:

Responsible Party: Dhanesh Gupta, Associate Professor of Anesthesiology & Neurological Surgery, Northwestern University
ClinicalTrials.gov Identifier: NCT01677650     History of Changes
Other Study ID Numbers: STU00064915
Study First Received: August 30, 2012
Last Updated: January 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
Spinal Fusion
Opioid Analgesia

Additional relevant MeSH terms:
Methadone
Analgesics
Analgesics, Opioid
Antitussive Agents
Central Nervous System Agents
Central Nervous System Depressants
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014