Multicenter Perioperative Opioid Pharmacogenetic Study

January 30, 2017 updated by: Children's Hospital Medical Center, Cincinnati

Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children: A Multicenter Pharmacogenetic Study

The purpose of this research study is to identify factors and genes (the DNA material that determines the makeup of the human body) that may be associated with how children respond to pain medication. Specifically, the investigators want to study factors that may be associated with pain sensitivity, morphine requirement after surgery and side-effects from morphine and other pain medications. The investigators expect that the information obtained in this research study will help us to develop more effective, safe, and tailored treatment options in the future.

Study Overview

Status

Completed

Conditions

Detailed Description

Opioid drugs as a group have withstood the test of time in their ability to relieve pain. Morphine is the most frequently used "gold standard" opioid for managing surgical pain. Like other opioids, morphine has a narrow therapeutic index and a large inter-patient variability in response. Certain genetic and non-genetic factors are believed to be responsible for variations in analgesic responses and side effects with morphine. Genetic factors determining an individual's pain sensitivity and regulating morphine's pharmacokinetics (transporters) and pharmacodynamics (receptors and signal transduction elements) are likely contributors to such variability. Frequent variations in analgesic response are unfortunately clinically significant with inadequate pain relief at one end of the spectrum of responses and major side effects including potentially fatal respiratory depression due to relative overdosing at the other end. Much of the inter-individual variability in response to a dose of morphine following surgical procedures can be explained by single nucleotide polymorphisms (SNPs) in a subset of the genes that encode proteins involved in pain perception, opioid transport and opioid receptor signaling. The genetic variants of mu opioid receptor (OPRM1), Catechol-O-methyltransferase (COMT), the Multi Drug Resistance Transport protein gene ABC B1, have been associated in small adult studies with varying levels of pain sensitivity, analgesic response to opioids and susceptibility to serious side-effects of opioids such as respiratory depression, sedation and vomiting. Effective and safe acute postoperative pain relief in a subset of children is clinically difficult due to frequent clinical variations in perceptions of pain and responses to opioids. To the investigator's knowledge, there is no other study attempting to individualize perioperative analgesia in children. The investigator's long term goal is to identify factors that modify pain sensitivity and responses to morphine in order to develop more effective, safe and tailored therapies. The overall objective of this application is to evaluate the contribution of individual and combined affects of genetic polymorphisms in OPRM1, COMT and ABC B1 genes and their association with postoperative pain relief and adverse effects with morphine. The investigator's central hypothesis is that specific genetic polymorphisms in genes involved in pain perception, opioid transport and opioid receptor signaling pathways contribute significantly to pain sensitivity, morphine consumption, and morphine's side-effects in children.

This study will also explore a set of other important SNPs that might influence pain perception and responses to morphine in children. The data will be analyzed looking at pain scores, morphine doses, incidence of side-effects of morphine including respiratory depression, sedation, vomiting and itching.

Study Type

Observational

Enrollment (Actual)

1000

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
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital of Los Angeles
      • Palo Alto, California, United States, 94304
        • Stanford University Medical Center
    • Colorado
      • Denver, Colorado, United States, 80045
        • The Children's Hospital, Denver
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami - Miller School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center for Children
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • C.S. Mott Children's Hospital
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • St. Louis Children's Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19134
        • St. Christopher's Hospital for Children
    • Texas
      • Houston, Texas, United States, 77094
        • Texas Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • UW Health-American Family Children's 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

Ages Eligible for Study

6 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Children undergoing adenotonsillectomy in the United States.

Description

Inclusion Criteria:

  • children 6-17 years of age
  • ASA physical status 1 and 2
  • scheduled for tonsillectomy (T) and tonsillectomy and adenoidectomy (T and A)
  • Children with obstructive sleep apnea will also be included.

Exclusion Criteria:

  • children with developmental delay
  • liver and renal diseases,
  • preoperative pain requiring analgesics (e.g. chronic tonsillitis).

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Outcomes
Time Frame: Post-anesthetic recovery room, an expected average of 2 hours
Incidence of serious opioid related adverse effects including respiratory depression, excessive sedation, nausea and vomiting in recovery room.
Post-anesthetic recovery room, an expected average of 2 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy Outcome Measures - Opioid interventions
Time Frame: Post-anesthetic recovery room, an expected average of 2 hours
Number of opioid interventions required in the recovery room
Post-anesthetic recovery room, an expected average of 2 hours
Efficacy Outcome Measures - Opioid requirement
Time Frame: Post-anesthetic recovery room, an expected average of 2 hours
Total opioid requirement will be measured
Post-anesthetic recovery room, an expected average of 2 hours
Efficacy Outcome Measures - Pain Scores
Time Frame: Post-anesthetic recovery room, an expected average of 2 hours
Pain scores as measured by the Numerical Rating Scale (NRS) and the Facial expression, Leg movement, Activity, Cry, and Consolability (FLACC) Scale
Post-anesthetic recovery room, an expected average of 2 hours

Collaborators and Investigators

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

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

Johns Hopkins University
Baylor College of Medicine
University of Miami
University of Michigan
Children's Hospital Colorado
Boston Children's Hospital
University of Wisconsin, Madison
Seattle Children's Hospital
Stanford University
Ann & Robert H Lurie Children's Hospital of Chicago
University of Utah
Children's Hospital Los Angeles
St. Louis Children's Hospital
Shanghai Children's Hospital
Phoenix Children's Hospital
C.S. Mott Children's Hospital
Ochsner Health System
St. Christopher's Hospital for Children

Investigators

  • Principal Investigator: Senthilkumar Sadhasivam, Children's Hospital Medical Center, Cincinnati

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 (Actual)

November 1, 2010

Primary Completion (Actual)

January 1, 2016

Study Completion

April 30, 2017

Study Registration Dates

First Submitted

December 12, 2011

First Submitted That Met QC Criteria

December 16, 2011

First Posted (Estimate)

December 20, 2011

Study Record Updates

Last Update Posted (Estimate)

January 31, 2017

Last Update Submitted That Met QC Criteria

January 30, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 2010-1353

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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