Personalized Perioperative Analgesia Platform (PPAP) for Pediatric Spine Fusion Surgery (sIRB) (PPAP Spine)

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.

Study Overview

• Status: Recruiting
• Conditions: Spine Fusion; PPAP
• Intervention / Treatment: Diagnostic test: Preoperative Genotyping

Detailed Description

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)

1. 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.

2. 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

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Senthilkumar Sadhasivam, MD, MPH; Phone Number: 4126472994; Email: sadhasivams@upmc.edu
• Study Contact Backup: Name: Dayana Alsamsam, BSPS, MSc; Email: alsamsamd@upmc.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 38456
      • Recruiting
      • University of California
      • Contact: Ridhima Jain; Email: Ridhma.jain@ucsf.edu
      • Principal Investigator: Anshuman Sharma
  • Florida
    • St. Petersburg, Florida, United States, 33701
      • Not yet recruiting
      • Johns Hopkins All Children's Hospital
      • Contact: Frederick Kuo, MD; Phone Number: 410-929-2123; Email: frederick.kuo@jhmi.edu
      • Contact: Janelle Maddox-Regis, MS, CIP; Phone Number: 443-927-1476; Email: Jmaddox3@jhmi.edu
      • Principal Investigator: Frederick Kuo, MD
    • St. Petersburg, Florida, United States, 33701
      • Not yet recruiting
      • Children's Orthopaedic and Scoliosis Surgery Associates, LLP
      • Contact: Ryan E. Fitzgerald, MD; Phone Number: 813-506-5511; Email: rfitzgerald@chortho.com
      • Contact: Priscilla Martinez; Phone Number: 813-506-5511; Email: pmartinez@chortho.com
      • Principal Investigator: Ryan E. Fitzgerald, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Riley Children's Hospital
      • Contact: Senthil Packiasabhapathy, MD; Email: sepack@iu.edu
      • Principal Investigator: Senthil Packiasabhapathy, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • UPMC Children's Hospital
      • Contact: Senthilkumar Sadhasivam, MD, MPH; Phone Number: 412-647-2994; Email: sadhasivams@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children ages 10 to 21
• ASA physical status 1 to 3
• Undergoing Posterior-Lateral Spinal Fusion
• Receives in-patient opioids
• Prescribed opioids at discharge

Exclusion Criteria:

• Serious illness
• Preoperative severe pain
• Preoperative opioid use or misuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Children undergoing Spine Fusion Surgery; This arm will include approximately 300 children undergoing spine fusion surgery; Pharmacokinetic (PK): collection of 10-13 serial blood samples to determine serum levels of methadone/oxycodone and its metabolites; Pharmacogenetic (PG): Preoperative CYP2D6 genotyping (for preferential recruitment of CYP2D6 PMs and UMs). This will be collected in the pre-operative clinic via blood if there are clinical labs needed for standard of care. If no blood is needed in the pre-op clinic, the investigators will collect this via saliva. 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.

Diagnostic test: Preoperative Genotyping; Genotype based risk prediction and personalized pain management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	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.	Pre-operative to post-operative day 2

Other Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Senthil Sadhasivam
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Senthilkumar Sadhasivam, MD, MPH, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2022
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: May 4, 2022
• First Posted (Actual): May 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Pediatric; PPAP; Spine Fusion Surgery
• Other Study ID Numbers: STUDY21090075; TR003719 (Other Grant/Funding Number: National Institutes of Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No current IPD sharing plan anticipated

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No