Pharmacogenomics of Methadone in Spine Fusion Surgery

Northwestern University

Status and phase: Withdrawn; Phase 1

Conditions: Scoliosis; Kyphosis

Treatments: Drug: Methadone

Study type: Interventional

Funder types: Other

Identifiers

NCT01677650

STU00064915

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 5 patient groups

Methadone 0.5 mg/kg

Active Comparator group

Description:

Methadone 0.5 mg/kg

Treatment:

Drug: Methadone

Methadone 0.4 mg/kg

Experimental group

Description:

Methadone 0.4 mg/kg

Treatment:

Drug: Methadone

Methadone 0.3 mg/kg

Active Comparator group

Description:

Methadone 0.3 mg/kg

Treatment:

Drug: Methadone

Methadone 0.2 mg/kg

Active Comparator group

Description:

Methadone 0.2 mg/kg

Treatment:

Drug: Methadone

Methadone 0.15 mg/kg

Active Comparator group

Description:

Methadone 0.15 mg/kg

Treatment:

Drug: Methadone