Multicenter Perioperative Opioid Pharmacogenetic Study

Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01495611
• Other study ID #: 2010-1353
• Status: Completed
• Phase: N/A
• First received: December 12, 2011
• Last updated: January 30, 2017
• Start date: November 2010
• Est. completion date: April 30, 2017

Study information

• Verified date: January 2017
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: April 30, 2017
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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).

Related Conditions & MeSH terms

• Pain

Locations

Country	Name	City	State
United States	C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	The Children's Hospital, Denver	Denver	Colorado
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	UW Health-American Family Children's Hospital	Madison	Wisconsin
United States	University of Miami - Miller School of Medicine	Miami	Florida
United States	Ochsner Medical Center for Children	New Orleans	Louisiana
United States	Stanford University Medical Center	Palo Alto	California
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington
United States	St. Louis Children's Hospital	St. Louis	Missouri

Sponsors (19)

Lead Sponsor

Collaborator

Children's Hospital Medical Center, Cincinnati

Ann & Robert H Lurie Children's Hospital of Chicago, Boston Children’s Hospital, C.S. Mott Children's Hospital, Children's Hospital Colorado, Children's Hospital Los Angeles, Johns Hopkins University, Ochsner Health System, Phoenix Children's Hospital, Seattle Children's Hospital, Shanghai Children's Hospital, St. Christopher's Hospital for Children, St. Louis Children's Hospital, Stanford University, Texas Children's Hospital, University of Miami, University of Michigan, University of Utah, UW Health American Family Children's Hospital/University of Wisconsin

Country where clinical trial is conducted

United States, 

References & Publications (41)

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* Note: There are 41 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Outcomes	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	Efficacy Outcome Measures - Opioid interventions	Number of opioid interventions required in the recovery room	Post-anesthetic recovery room, an expected average of 2 hours
Secondary	Efficacy Outcome Measures - Opioid requirement	Total opioid requirement will be measured	Post-anesthetic recovery room, an expected average of 2 hours
Secondary	Efficacy Outcome Measures - Pain Scores	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