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| ID | Type | Description | Link |
|---|---|---|---|
| TR003719 | Other Grant/Funding Number | National Institutes of Health |
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| Name | Class |
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| National Institute on Drug Abuse (NIDA) | NIH |
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The purpose of this collaborative CTSA application is to develop an innovative perioperative precision analgesia platform (PPAP) to improve analgesia and reduce serious immediate and long-term adverse outcomes of perioperative opioids in children undergoing painful surgery.
Aim 1. Develop and implement a perioperative precision analgesia platform (PPAP) by linking genomics to opioid metabolism, CPIC guidelines, precision dosing, clinical safety, and personalizing analgesia.
Aim 2. Implement and evaluate PPAP in children undergoing major inpatient surgery, posterior spinal fusion (PSF)
Determine genetic factors predisposing children to immediate and long-term postoperative methadone and oxycodone related adverse effects including RD, PONV, opioid dependence, and CPSP
The PI postulate that specific CYP2B6, ABCB1, OPRM1, FAAH, and CYP2D6 variants identify children at risk for poor pain relief, RD, PONV, opioid dependence, and CPSP in the postoperative period.
Determine genetic variants-based perioperative dosing and outpatient prescribing of opioids
The PI hypothesize that CYP2B6 and CYP2D6 variants will explain pharmacokinetic variations of methadone and oxycodone, determine the right doses, and implement precision opioid use for optimal clinical outcomes
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Children undergoing Spine Fusion Surgery | Other | This arm will include approximately 300 children undergoing spine fusion surgery
Postoperative Analgesia Dose and PK Sampling Schedule: Clinical care providers are blinded to CYP2D6/CYP2B6 when prescribing oxycodone/methadone; and genetic analysis of proposed targeted genes. Results of these samples will be used to determine personalized analgesia plan. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Preoperative Genotyping | Diagnostic Test | Genotype based risk prediction and personalized pain management |
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| Measure | Description | Time Frame |
|---|---|---|
| Look at genetic factors predisposing children to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (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 | Immediately post-surgery up to 4 days in patient |
| Look at genetic factors predisposing children to postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV) 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 RD and PONV in the post-surgical period at home up to 1-year | 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. Poor pain relief will be determined using the Numerical Rating Scale (NRS) which runs on a 0-10 scale; 0 being no pain at all, 10 being the worst pain imaginable. | Immediately 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 post-surgical period at home up to 1-year. Poor pain relief will be determined using the Numerical Rating Scale (NRS) which runs on a 0-10 scale; 0 being no pain at all, 10 being the worst pain imaginable. | 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 sampling and the need for dose adjustments that lead to desired clinical outcomes in children undergoing major inpatient surgeries. Oxycodone will be measured by the IU CTSI's Clinical Pharmacology Analytical Core (CPAC) laboratory using a validated LC/MS/MS as-say,201 and plasma alpha-1 acid glycoprotein (AAG) will be measured using a HPLC/UV assay. Study team will track the subjects choices from their signed consent form regarding PK collections. |
| Measure | Description | Time Frame |
|---|---|---|
| Look at OPRM1 epigenetics and OPRM1, FAAH, GCH1, DRD2 variants to find correlations with chronic persistent surgical pain (CPSP) up to 1-year post-surgery | Children will be asked to complete psychological questionnaires post-surgery to assess psycho-psychological factors that may correlate with CPSP. CPSP is defined as pain that develops after a surgical procedure and lasts at least 3 months and significantly affects health-related quality of life. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Senthilkumar Sadhasivam, MD, MPH | Contact | 4126472994 | sadhasivams@upmc.edu | |
| Dayana Alsamsam, BSPS, MSc | Contact | alsamsamd@upmc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Senthilkumar Sadhasivam, MD, MPH | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California | Recruiting | San Francisco | California | 38456 | United States |
No current IPD sharing plan anticipated
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PK sampling and genetic testing will determine the type of analgesia medication treatment the patient receives
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| Pre-operative to post-operative day 2 |
| Post-operative up to 1-year |
| Look at OPRM1 epigenetics and OPRM1, FAAH, GCH1, DRD2 variants to find correlations with opioid dependence (OD) up to 1-year post-surgery | Children will be asked to complete psychological questionnaires post-surgery to assess psycho-psychological factors that may correlate with opioid dependence (OD). OD will be determined using the validated Sophia Observation Withdrawal Symptoms Scale and the Clinical Opiate Withdrawal Scale (COWS). The Sophia Observation Withdrawal Symptoms Scale is based on a 15-point scale. The COWS is based on a scale with a minimum score of 5 and maximum score of 48; 5-12 = mild, 13-24 = moderate, 25-36 = moderately severe, more than 36 = severe withdrawal | Post-operative up to 1-year |
| Children's Orthopaedic and Scoliosis Surgery Associates, LLP | Not yet recruiting | St. Petersburg | Florida | 33701 | United States |
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| Johns Hopkins All Children's Hospital | Not yet recruiting | St. Petersburg | Florida | 33701 | United States |
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| Riley Children's Hospital | Recruiting | Indianapolis | Indiana | 46202 | United States |
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| UPMC Children's Hospital | Recruiting | Pittsburgh | Pennsylvania | 15224 | United States |
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