Pharmacogenomics of Methadone in Spine Fusion Surgery

April 21, 2015 updated by: Dhanesh Gupta, Northwestern University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Methadone 0.5 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Other Names:
  • Dolophine
Experimental: Methadone 0.4 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Other Names:
  • Dolophine
Active Comparator: Methadone 0.3 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Other Names:
  • Dolophine
Active Comparator: Methadone 0.2 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Other Names:
  • Dolophine
Active Comparator: Methadone 0.15 mg/kg
Drug: Methadone
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg
Other Names:
  • Dolophine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Time until initial request for postoperative analgesic.
Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
60 minutes after extubation, 24, 48, and 72 hours after methadone administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The determination of minimum effective analgesic concentration of methadone.
Time Frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
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
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
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
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
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
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
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
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
24, 48, and 72 hours after methadone administration
Patient analgesic satisfaction
Time Frame: 24, 48, and 72 hours after methadone administration
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
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
Preoperatively
Pupillometry for assessment of sedation
Time Frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Northwestern University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dhanesh K. Gupta, M.D., Northwestern University Feinberg School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2015

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 31, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 3, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STU00064915

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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