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

Spine Fusion Clinical Trial

— PPAP Spine  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05367609
• Other study ID #: STUDY21090075
• Secondary ID: TR003719
• Status: Recruiting
• Phase: N/A
• Start date: September 20, 2022
• Est. completion date: September 2025

Study information

• Verified date: November 2023
• Source: University of Pittsburgh
• Contact: Senthilkumar Sadhasivam, MD, MPH
• Phone: 4126472994
• Email: sadhasivams[@]upmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 investigators 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 investigators 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: September 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Spine Fusion

Intervention

Diagnostic Test:
• Preoperative Genotyping
Genotype based risk prediction and personalized pain management

Locations

Country	Name	City	State
United States	Riley Children's Hospital	Indianapolis	Indiana
United States	UPMC Children's Hospital	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Senthil Sadhasivam	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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
Primary	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
Primary	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
Secondary	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