Pharmacogenomics Analysis of Morphine Pharmacokinetics in Pediatric Tonsillectomy and Adenoidectomy
|ClinicalTrials.gov Identifier: NCT00836264|
Recruitment Status : Suspended (Enrollment is on hold dependent upon funding)
First Posted : February 4, 2009
Last Update Posted : January 20, 2017
Intravenous (IV) morphine requirement for immediate postoperative pain control depends upon the complex interplay of patient history, wound severity, environment, and genetics. Even for relatively uniform stimulus intensity, such as that associated with tonsillectomy and adenoidectomy (T&A), there can be marked individual variability in response to morphine. Some patients are refractory to standard doses and need increased amounts. Others are sensitive, require less drug to attain acceptable pain levels, and/or experience unwanted side effects that limit dosing. A significant number must be switched to different analgesics altogether. Despite the long clinical history of morphine as a postoperative analgesic, researchers have only begun to examine the origins of response variability.
The investigators will look at 2000 retrospective Tonsillectomy and Adenoidectomy cases and using this data and incorporating additional patient, surgical, and environmental factors that may contribute to response variability, the investigators then propose a prospective genome-wide association (GWA) study of 1500 children ages 4 to 18 y treated with IV morphine sulfate for day surgery T&A.
|Condition or disease|
|Tonsillectomy Adenoidectomy Pharmacokinetics|
Morphine Tonsilectomy and Adenoidectomy (T&A) Pharmacokinetics (PK) study will be done as a part of the larger institutional Center for Applied Genomics (CAG) project entitled "A Study of the Genetic Causes of Complex Pediatric Disorders" (GCPD study), as approved by the Children's Hospital of Philadelphia (CHOP) IRB, 2006-7-4886. By combining Genome Wide Association (GWA) and PK data, we wish to conduct a Pharmacogenomic (PG) study of IV morphine administered as standard of care during and after pediatric day surgery T&A. Because we expect several genes to play a role in the morphine response, we must use a large, relatively uniform pediatric surgical population such that for T&A. Through observation and minimal-risk blood sampling of this cohort of children, we hope to identify genetic variants that predict analgesic response to (and serum levels of) morphine sulfate. Pediatric patients ages 4-18 y, presenting with significant tonsillar/adenoidal tissue hypertrophy, sleep disordered breathing and/or recurrent infection, and requiring T&A are eligible. Morphine is the most common IV analgesic used for T&A at CHOP. As is necessary for accurately defining analgesic response phenotype, morphine will be administered in a structured manner consistent with standard of care at this institution. As defined below, children resistant to morphine (MR) and those sensitive to it (MS) will be identified as specific phenotypes to be compared with normal responders (NR) in a GWA study.
This study begins with a retrospective electronic database query of 2000 day surgery T&A cases between 11/1/2005 and 10/31/2008 in which morphine was used as the sole IV analgesic. Data from this portion of the study will help us refine phenotype parameters, should robust subpopulations of response types emerge, and provide background information required for eventual project funding by the National Institutes of Health (NIH). The prospective portion of the study will follow an additional 1650 children newly enrolled in the CAG study and now presenting for T&A.
|Study Type :||Observational|
|Estimated Enrollment :||1650 participants|
|Official Title:||Pharmacogenomic Analysis of Morphine Pharmacokinetics and Response Variability Following Pediatric Tonsillectomy and Adenoidectomy: A Genome-Wide Association Approach|
|Actual Study Start Date :||December 2015|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||June 2019|
Morphine T & A
Subjects ages 4-18 years of age who have a Tonsillectomy and Adenoidectomy and receive morphine for pain control and who have also enrolled in the CAG study at CHOP, "A Study of the Genetic Causes of Complex Pediatric Disorders" (GCPD study), as approved by the CHOP IRB, 2006-7-4886.
- The primary endpoint will be to identify genetic variants that contribute to the variability of morphine analgesic response following pediatric day surgery T&A. [ Time Frame: 2 years ]
Biospecimen Retention: Samples Without DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00836264
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Scott Cook-Sather, MD||Children's Hospital of Philadelphia|