Multicenter Perioperative Opioid Pharmacogenetic Study

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Texas Children's Hospital
Ochsner Medical Center for Children
Children's Hospital Colorado
Children's Hospital Los Angeles
C.S. Mott Children's Hospital
St. Christopher's Hospital for Children
St. Louis Children's Hospital
Children's Hospital Boston
Seattle Children's Hospital
Ann & Robert H Lurie Children's Hospital of Chicago
UW Health American Family Children's Hospital
University of Miami
Johns Hopkins University
Stanford University
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01495611
First received: December 12, 2011
Last updated: September 17, 2013
Last verified: September 2013
  Purpose

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.


Condition
Pain

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children: A Multicenter Pharmacogenetic Study

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Safety Outcomes [ Time Frame: Post-anesthetic recovery room, an expected average of 2 hours ] [ Designated as safety issue: Yes ]
    Incidence of serious opioid related adverse effects including respiratory depression, excessive sedation, nausea and vomiting in recovery room.


Secondary Outcome Measures:
  • Efficacy Outcome Measures - Opioid interventions [ Time Frame: Post-anesthetic recovery room, an expected average of 2 hours ] [ Designated as safety issue: No ]
    Number of opioid interventions required in the recovery room

  • Efficacy Outcome Measures - Opioid requirement [ Time Frame: Post-anesthetic recovery room, an expected average of 2 hours ] [ Designated as safety issue: No ]
    Total opioid requirement will be measured

  • Efficacy Outcome Measures - Pain Scores [ Time Frame: Post-anesthetic recovery room, an expected average of 2 hours ] [ Designated as safety issue: No ]
    Pain scores as measured by the Numerical Rating Scale (NRS) and the Facial expression, Leg movement, Activity, Cry, and Consolability (FLACC) Scale


Biospecimen Retention:   Samples With DNA

A database/ repository will be constructed for future research, analysis, and recruitment. De-identified study subjects' genetic information and their responses to pain and pain medications, side-effects will be included in the database. Blood specimens will be included in the repository for exploring potentially important SNPs and biomarkers in future. No patient identifiers will be included in the repository and there will be a confidential (access limited to investigators only) code or link between the repository/database and other information about the participant.


Estimated Enrollment: 1000
Study Start Date: November 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Children undergoing adenotonsillectomy in the United States.

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).
  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: NCT01495611

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

Publications:
Seid M, Varni J. Pediatric day surgery outcomes management: The role of preoperative anxiety and a home pain management protocol. JCOM 1999;6:24-30.

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01495611     History of Changes
Other Study ID Numbers: 2010-1353
Study First Received: December 12, 2011
Last Updated: September 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Medical Center, Cincinnati:
postoperative,
pediatric
pharmacogenetic
opioid
morphine
perioperative
respiratory depression

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

ClinicalTrials.gov processed this record on August 21, 2014