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| ID | Type | Description | Link |
|---|---|---|---|
| 7R01HD089458-02 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Children's Hospital Medical Center, Cincinnati | OTHER |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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Each year, in the U.S. alone, >6 million children undergo painful surgery; up to 50% of them experience significant and serious side effects with opioids and inadequate pain relief. Though 60% of this inter-individual variability in responses results from genetic variations, there is an almost complete lack of understanding of how specific genetic variability affects pain and of the adverse effects of opioids, especially in children. In this project the investigators will focus on oxycodone, a standard and preferred post-surgical oral analgesic in children
The purpose of this research is to study serious immediate and long-term clinical problems from both surgical pain and oxycodone use in children and adolescents to improve the safety and effectiveness of surgical pain relief.
The long-term goals are to improve the safety and effectiveness of surgical pain relief with opioids (a class of drugs/pain relievers) and to minimize the societal burden of disabling Chronic Persistent Surgical Pain (CPSP, which is pain that persists even after the expected healing time from surgery) and Opioid Dependence (OD) by preoperative risk predictions and personalized care with the right dose of the right pain medication for each child.
The overall objective is to determine the impact of risk factors on oxycodone's immediate and long-term negative postoperative outcomes and to personalize dosing in children undergoing outpatient and major inpatient surgery.
Research procedures will include:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Major Inpatient Surgeries | Children ages 8-17.9 undergoing pectus excavatum or idiopathic scoliosis spinal fusion at Riley Hospital for Children, who have consented to participate in an observational clinical study as approved by the IU IRB, protocol #1707525204. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxycodone | Drug | Post-op pain management medication |
|
| Measure | Description | Time Frame |
|---|---|---|
| Look at genetic factors predisposing children to immediate postoperative opioid-adverse effects (RD and PONV). | The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience RD, and PONV in the immediate post-surgical period (4 days) in the hospital and at home. | Immediately post-surgery during hospital stay and at home up to 1 year post-surgery |
| Look at genetic factors predisposing children to inadequate surgical pain relief with oxycodone. | The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience poor pain relief in the immediate post-surgical period (4 days) in the hospital and at home. | Immediately post-surgery during hospital stay and at home up to 1 year post-surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Look at the impact of CYP2D6 variants on oxycodone's clinical dosing in children to see if specific variants correlate with a need for lower or higher doses of analgesic. | The investigators will look at CYP2D6 variants to find correlations in oxycodone's PK variability and the need for dose adjustments that lead to desired clinical outcomes in children undergoing major inpatient surgeries. | Pre-operative to post-operative day 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Look at genetic oxycodone-related perioperative and bio-psychological factors predisposing children to long-term adverse outcomes such as chronic persistant surgical pain and opioid dependence. | The investigators will look at OPRM1 epigenetics and OPRM1, FAAH, GCH1, DRD2 variants to find correlations with chronic persistent surgical pain and opioid dependence up to 1 year post-surgery. Children will also be asked to complete psychological questionnaires pre-surgery, and at 4 time points post-surgery to assess psycho-psychological factors that may correlate with chronic persistent surgical pain or opioid dependence. |
Inclusion Criteria:
Exclusion Criteria:
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Pectus excavatum repair and spinal fusions are two of the most painful surgery children and adolescents undergo. Therefore, the investigators aim to recruit 500 children and adolescents, 8-17.9 years of age, undergoing inpatient pectus excavatum repair or idiopathic scoliosis spinal fusions at Riley Hospital for Children.
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| Name | Affiliation | Role |
|---|---|---|
| Senthilkumar Sadhasivam, MD, MPH | University of Pittsburgh, UPMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Riley Hospital for Children | Indianapolis | Indiana | 46202 | United States | ||
| UPMC Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36946298 | Derived | Aruldhas BW, Quinney SK, Packiasabapathy S, Overholser BR, Raymond O, Sivam S, Sivam I, Velu S, Montelibano A, Sadhasivam S. Effects of oxycodone pharmacogenetics on postoperative analgesia and related clinical outcomes in children: a pilot prospective study. Pharmacogenomics. 2023 Mar;24(4):187-197. doi: 10.2217/pgs-2022-0149. Epub 2023 Mar 22. | |
| 34100292 | Derived | Packiasabapathy S, Aruldhas BW, Zhang P, Overholser BR, Quinney SK, Sadhasivam S. Novel associations between CYP2B6 polymorphisms, perioperative methadone metabolism and clinical outcomes in children. Pharmacogenomics. 2021 Jul;22(10):591-602. doi: 10.2217/pgs-2021-0039. Epub 2021 Jun 8. |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D010098 | Oxycodone |
| ID | Term |
|---|---|
| D003061 | Codeine |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
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DNA from blood is obtained and analyzed for genetic variations
| Pre-operative to 12 months post-operative |
| Pittsburgh |
| Pennsylvania |
| 15224 |
| United States |
| 33481403 | Derived | Sadhasivam S, Aruldhas BW, Packiasabapathy S, Overholser BR, Zhang P, Zang Y, Renschler JS, Fitzgerald RE, Quinney SK. A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects. Anesth Analg. 2021 Aug 1;133(2):327-337. doi: 10.1213/ANE.0000000000005366. |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| D000470 |
| Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |