Clinical trial NCT01495611: Multicenter Perioperative Opioid Pharmacogenetic Study
Official title: Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children: A Multicenter Pharmacogenetic Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pain
Keywords: postoperative,
pediatric
pharmacogenetic
opioid
morphine
perioperative
respiratory depression
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Baylor College of Medicine
name: Ochsner Health System
name: Children's Hospital Colorado
name: Children's Hospital Los Angeles
name: C.S. Mott Children's Hospital
name: St. Christopher's Hospital for Children
name: St. Louis Children's Hospital
name: Boston Children's Hospital
name: Seattle Children's Hospital
name: Ann & Robert H Lurie Children's Hospital of Chicago
name: University of Wisconsin, Madison
name: University of Miami
name: Johns Hopkins University
name: Stanford University
name: Phoenix Children's Hospital
name: University of Michigan
name: University of Utah
name: Shanghai Children's Hospital
First posted: 2011-12-20
Enrollment: 1000
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children undergoing adenotonsillectomy in the United States.

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.

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).

Primary outcomes:
measure: Safety Outcomes
timeFrame: Post-anesthetic recovery room, an expected average of 2 hours
Secondary outcomes:
measure: Efficacy Outcome Measures - Opioid interventions
timeFrame: Post-anesthetic recovery room, an expected average of 2 hours
measure: Efficacy Outcome Measures - Opioid requirement
timeFrame: Post-anesthetic recovery room, an expected average of 2 hours
measure: Efficacy Outcome Measures - Pain Scores
timeFrame: Post-anesthetic recovery room, an expected average of 2 hours
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: The Children's Hospital, Denver
state: Colorado
city: Miami
country: United States
facility: University of Miami - Miller School of Medicine
state: Florida
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Medical Center for Children
state: Louisiana
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: St. Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: UW Health-American Family Children's Hospital
state: Wisconsin
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Senthilkumar Sadhasivam
role: PRINCIPAL_INVESTIGATOR
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