Multicenter Perioperative Opioid Pharmacogenetic Study

NCT ID: NCT01495611

Last Updated: 2017-01-31

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2017-04-30

Brief Summary

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.

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.

Conditions

Pain

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

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).

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

Ochsner Health System

OTHER

Sponsor Role: collaborator

Children's Hospital Colorado

OTHER

Sponsor Role: collaborator

Children's Hospital Los Angeles

OTHER

Sponsor Role: collaborator

C.S. Mott Children's Hospital

OTHER

Sponsor Role: collaborator

St. Christopher's Hospital for Children

OTHER

Sponsor Role: collaborator

St. Louis Children's Hospital

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

Seattle Children's Hospital

OTHER

Sponsor Role: collaborator

Ann & Robert H Lurie Children's Hospital of Chicago

OTHER

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

Phoenix Children's Hospital

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: collaborator

Shanghai Children's Hospital

OTHER

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Senthilkumar Sadhasivam

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

Children's Hospital of Los Angeles

Los Angeles, California, United States

Stanford University Medical Center

Palo Alto, California, United States

The Children's Hospital, Denver

Denver, Colorado, United States

University of Miami - Miller School of Medicine

Miami, Florida, United States

Children's Memorial Hospital

Chicago, Illinois, United States

Ochsner Medical Center for Children

New Orleans, Louisiana, United States

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Boston Children's Hospital

Boston, Massachusetts, United States

C.S. Mott Children's Hospital

Ann Arbor, Michigan, United States

St. Louis Children's Hospital

St Louis, Missouri, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Texas Children's Hospital

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

UW Health-American Family Children's Hospital

Madison, Wisconsin, United States

Countries

United States

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Other Identifiers

2010-1353

Identifier Type: -

Identifier Source: org_study_id