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Personalizing Perioperative Analgesia in Children

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ClinicalTrials.gov Identifier: NCT01140724
Recruitment Status : Active, not recruiting
First Posted : June 9, 2010
Last Update Posted : December 20, 2017
Sponsor:
Collaborators:
Children's Hospital Medical Center, Cincinnati
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Senthilkumar Sadhasivam, MD, MPH, Indiana University

Brief Summary:
In the United States alone, each year approximately 5 million children undergo painful surgery, many of them experience serious side-effects with opioids and inadequate pain relief. Safe and effective analgesia is an important unmet critical medical need in children and its continued existence is an important perioperative safety and economic problem. Inadequate pain relief and serious side effects from perioperative opioids occur frequently in up to 50% of children. Morphine, the most commonly used perioperative opioid, has a narrow therapeutic index and large inter-patient variations in analgesic response and serious side effects. Frequent inter-individual variations in responses to morphine have significant clinical and economic impact with inadequate pain relief at one end of the spectrum of responses and serious adverse effects such as respiratory depression 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 mechanisms and opioid pathway.

Condition or disease
Postoperative Pain

Detailed Description:

Measures and Procedures: Participants will receive standard care, standard anesthetic and an intraoperative dose of morphine per the clinical team.

Research procedures will include:

  1. Blood draws for genotyping candidate genes and exploratory genes
  2. Standardized PACU (post anesthesia care unit) Protocol: Subjective pain assessments: Numerical Rating Scale (NRS) 0 to 10. Objective assessment with FLACC (facial expression; leg movement; activity; cry; and consolability) scale, 0-10.
  3. Significant postoperative pain will be managed in the PACU with rescue doses of morphine and opioids by the clinical team. Analgesic interventions and morphine requirements are collected
  4. Effects of opioids on pupil measures
  5. Respiratory response to 5% carbon dioxide preoperatively and postoperatively (first 350 patients only). Another measure of end tidal carbon dioxide will be implemented when the device is clinically available.
  6. Serial blood draws for morphine pharmacokinetic modeling (through subject #351).
  7. Opioid adverse effects in PACU and at home.

Study Type : Observational
Estimated Enrollment : 1200 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children
Study Start Date : April 2008
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2018



Primary Outcome Measures :
  1. Look at polymorphisms in genes that regulate pain perception, opioid transport and opioid receptor signaling to see if there is a higher susceptibility to pain and morphine requirement. [ Time Frame: After tonsillectomy surgery (duration of post anesthesia care unit stay) ]
    Look at polymorphisms in genes that regulate pain perception, opioid transport and opioid receptor signaling to see if there is a relationship to more pain and need for a higher morphine requirement.


Secondary Outcome Measures :
  1. Evaluate relationship of pupil reaction and response to 5% carbon dioxide to adverse effects of morphine [ Time Frame: After tonsillectomy surgery (duration of post anesthesia care unit stay) ]

Other Outcome Measures:
  1. Evaluate contribution of polymorphisms in genes to variability in codeine response in children with CYP2D6 genotypes predictive of extensive metabolizer or ultra-extensive metabolizer phenotypes [ Time Frame: During tonsilectomies ]
    Evaluate contribution of polymorphisms in genes that regulate pain perception, opioid transport and opioid receptor signaling to variability in codeine response in children with CYP2D6 genotypes predictive of extensive metabolizer or ultra-extensive metabolizer phenotypes

  2. Evaluate whether machine learning techniques can be used to predict pain response, opioid responses and morphine usage requirements in patients [ Time Frame: After tonsilectomy surgery data collection ]
    Evaluate whether machine learning techniques can be used to predict pain response, opioid responses and morphine usage requirements in patients solely using information extracted from the medical record as well as in combination with other genetic information


Biospecimen Retention:   Samples With DNA
DNA from blood is obtained and analyzed for genetic varaiations


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Ages Eligible for Study:   6 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Children, 6-15 years of age, undergoing tonsillectomy or adenotonsillectomy at the Riley Hospital for Children, who have consented to participate in an observational clinical study as approved by the IU IRB, protocol # 1707325115.
Criteria

Inclusion Criteria:

  • boys and girls,
  • 6-15 years of age,
  • all races,
  • American Society of Anesthesiologists (ASA) physical status 1 and 2,
  • children with history of significant snoring suggestive of obstructive sleep apnea (OSA.)

Exclusion Criteria:

  • allergic to study medications
  • developmental delay,
  • liver and renal diseases,
  • preoperative pain requiring analgesics,
  • children who have problems with pupil or pupillary reaction due to disease
  • preoperative medications influencing pupillary size
  • non-English speaking participants and families
  • Body Mass Index ≥30
  • Participants undergoing additional procedures during surgery
  • Children with certain cardiac conditions
  • Children with severe lung disease
  • Children with a history of seizures currently treated on medication
  • Children with psychiatric/psychological conditions for which patient currently takes medication

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01140724


Locations
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Indiana University
Children's Hospital Medical Center, Cincinnati
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Senthilkumar Sadhasivam, MD, MPH Indiana University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Senthilkumar Sadhasivam, MD, MPH, anesthesiologist in chief at Riley Hospital for Children, Indiana University
ClinicalTrials.gov Identifier: NCT01140724     History of Changes
Other Study ID Numbers: 1707325115
7R01HD089458-02 ( U.S. NIH Grant/Contract )
First Posted: June 9, 2010    Key Record Dates
Last Update Posted: December 20, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Senthilkumar Sadhasivam, MD, MPH, Indiana University:
pain
genes
morphine
respiratory depression
tonsillectomy
children
Opioid adverse effects
Pharmacogenetics of morphine
Pharmacokinetics of morphine
Personalizing analgesia

Additional relevant MeSH terms:
Pain, Postoperative
Pain
Neurologic Manifestations
Nervous System Diseases
Postoperative Complications
Pathologic Processes
Signs and Symptoms
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents