Multicenter Perioperative Opioid Pharmacogenetic Study
- Conditions
- Pain
- Registration Number
- NCT01495611
- Lead Sponsor
- Children's Hospital Medical Center, Cincinnati
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1000
- 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.
- children with developmental delay
- liver and renal diseases,
- preoperative pain requiring analgesics (e.g. chronic tonsillitis).
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety Outcomes 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.
- Secondary Outcome Measures
Name Time Method Efficacy Outcome Measures - Pain Scores 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
Efficacy Outcome Measures - Opioid requirement Post-anesthetic recovery room, an expected average of 2 hours Total opioid requirement will be measured
Efficacy Outcome Measures - Opioid interventions Post-anesthetic recovery room, an expected average of 2 hours Number of opioid interventions required in the recovery room
Trial Locations
- Locations (15)
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Miami - Miller School of Medicine
🇺🇸Miami, Florida, United States
C.S. Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Children's Memorial Hospital
🇺🇸Chicago, Illinois, United States
Ochsner Medical Center for Children
🇺🇸New Orleans, Louisiana, United States
The Children's Hospital, Denver
🇺🇸Denver, Colorado, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
UW Health-American Family Children's Hospital
🇺🇸Madison, Wisconsin, United States
St. Louis Children's Hospital
🇺🇸St. Louis, Missouri, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States