Trial record 2 of 16 for:    Open Studies | "Adenoidectomy"

Pharmacogenomics Analysis of Morphine Pharmacokinetics in Pediatric Tonsillectomy and Adenoidectomy

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by Children's Hospital of Philadelphia
Sponsor:
Collaborator:
Children's Anesthesiology Associates, Ltd.
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00836264
First received: February 2, 2009
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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
Tonsillectomy
Adenoidectomy
Pharmacokinetics

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacogenomic Analysis of Morphine Pharmacokinetics and Response Variability Following Pediatric Tonsillectomy and Adenoidectomy: A Genome-Wide Association Approach

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

PK plasma samples will be obtained


Estimated Enrollment: 1650
Study Start Date: December 2014
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   4 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Children having Tonsillectomy and Adenoidectomy procedures done at The Children's Hospital of Philadelphia, at the Main Hospital and also at the satellite surgical centers, who have also consented to participate in "A Study of the Genetic Causes of Complex Pediatric Disorders" (GCPD study), as approved by the CHOP IRB, 2006-7-4886.

Criteria

Inclusion Criteria:

  1. Concurrent enrollment in the GCPD study (IRB 2006-7-4886)
  2. Scheduled for day surgery T&A with expected same day discharge at CHOP Main in Philadelphia, Pennsylvania (PA) or the CHOP Ambulatory Surgical Facilities (ASFs) in Chalfont, PA; Exton, PA; or Voorhees, New Jersey (NJ)
  3. Male or female, age 4 - 18 y, all races and ethnic backgrounds
  4. Able to self-report pain on the Faces Pain Scale - Revised (FPS-R).
  5. Informed consent as addendum to GCPD consent document
  6. Assent for children ≥7 y of age

Exclusion Criteria:

  1. Parents/guardians or subjects who, in the opinion of the investigator, may be non-compliant with study schedules or procedures
  2. Non-English speaking subjects or parents. The reliability of the morphine analgesic requirement phenotype could be adversely affected by subtle communication differences between subjects and nursing staff assessing pain and administering morphine during patient recovery should language barriers exist. Parents must also be fluent in English as they will be at the bedside shortly after their child's arrival in recovery and could influence how their child understands pain scoring and how they interact with the nursing and research staff.
  3. Those parents/guardian or subjects not consenting to, or willing to participate in the GCPD study (IRB 2006-7-4886)
  4. Patients < 4 y of age were excluded to improve phenotype reliability. Due to a higher empirical risk of postoperative obstruction following T&A, children < 4 y of age are admitted for overnight observation. The titration of morphine is more difficult in these patients as clinicians generally follow more restrictive dosing regimens and the total morphine dose is drawn out over an extended period. Furthermore, the self-report Faces Pain Scale - Revised (FPS-R) has been validated for children ≥ 4 y and will be used to corroborate the morphine response phenotypes that are primarily based on morphine doses administered to achieve low Face, Legs, Activity, Cry, Consolability (FLACC) scores. The latter behavioral scoring is required for early morphine administration as children and adolescents emerging from anesthesia may have difficulty expressing themselves in the first 30 min. In addition, it is important for our statistical analysis to have a sequential scoring system over time that is applicable to all ages. Finally, the incidence of emergence agitation/delirium, a clinical phenomenon that shares some features of pain, but becomes distinct over 15-30 min, is higher in younger patients. (Sikich, 2004; Vlajkovic, 2007) By excluding children < 4 y we decrease the proportion of subjects whose FLACC scores may be high on the basis of emergence agitation/delirium.
  5. Significant comorbid conditions requiring a non-standard anesthetic regimen such as a history of severe post-operative nausea and vomiting requiring propofol infusion, a total intravenous anesthestic (TIVA) technique and/or mandating planned post-operative hospital admission
  6. Documented allergy or adverse reaction to morphine in the patient
  7. Use of opioids (e.g. codeine, oxycodone, morphine, hydromorphone) within the previous month
  8. Use of non-steroidal anti-inflammatory agents or acetaminophen in the 3 days preceding the T&A. No acetaminophen will be included in the premedication regimen on the day of surgery.
  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: NCT00836264

Contacts
Contact: Scott Cook-Sather, MD 215-590-1447 Sather@email.chop.edu
Contact: Theodora K. Goebel, RN, BSN 215-590-4925 goebelt@email.chop.edu

Locations
United States, Pennsylvania
The Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Scott Cook-Sather, MD    215-590-1447    sather@email.chop.edu   
Principal Investigator: Scott Cook-Sather, MD         
Sponsors and Collaborators
Children's Hospital of Philadelphia
Children's Anesthesiology Associates, Ltd.
Investigators
Principal Investigator: Scott Cook-Sather, MD Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00836264     History of Changes
Other Study ID Numbers: 2008-12-7023
Study First Received: February 2, 2009
Last Updated: July 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
Morphine
Phenotype
Genotype
Tonsillectomy
Adenoidectomy
Opioid Receptors
Genome-Wide Association
Pharmacokinetics

Additional relevant MeSH terms:
Morphine
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 September 18, 2014