Personalized Pain Management for Spinal Fusion

(PPAP Spine Trial)

Recruiting at 3 trial locations

Overseen By Carly Riedmann, MPH

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Senthilkumar Sadhasivam

Must be taking: Opioids

Disqualifiers: Serious illness, Preoperative severe pain, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to create a personalized pain management plan for children undergoing spinal fusion surgery. It focuses on a tailored approach to pain relief to reduce opioid use and potential side effects. Researchers will collect blood or saliva samples to understand how each child processes pain medication through Preoperative Genotyping (genetic testing for pain management). Children aged 10 to 21 who require spinal fusion surgery and will receive opioids afterward might be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to innovative pain management strategies for future pediatric patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who are using opioids before surgery.

What prior data suggests that the Personalized Perioperative Analgesia Platform (PPAP) and Preoperative Genotyping are safe for children undergoing spine fusion surgery?

Earlier studies have shown that personalized pain management methods, such as the Personalized Perioperative Analgesia Platform (PPAP), can improve pain relief and reduce the risks associated with opioid use after surgery. Research suggests that genetic testing before surgery can help customize pain medication doses, aiming to make pain treatment more effective and safer for each child.

While specific information on PPAP's side effects is not available, the focus on personalizing treatment indicates a careful approach to safety. Treatments in early research stages are still being tested for safety, so this trial likely collects important data to ensure it is safe and effective. If this personalized method proves successful, it could lead to better pain management with fewer side effects for children undergoing spinal surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Personalized Perioperative Analgesia Platform (PPAP) because it offers a tailored approach to pain management for children undergoing spinal fusion surgery. Unlike standard treatments that use a one-size-fits-all method for prescribing pain medications like methadone or oxycodone, PPAP customizes pain relief based on each child's genetic makeup (specifically, their CYP2D6 genotype). This personalized strategy aims to optimize pain control while minimizing side effects, potentially enhancing recovery and overall patient experience. By leveraging pharmacogenetics, PPAP represents a significant advancement in targeting pain management more precisely and effectively.

What evidence suggests that the Personalized Perioperative Analgesia Platform (PPAP) could be effective for pain management in children undergoing spinal fusion surgery?

Research has shown that personalized pain management can significantly enhance pain relief after surgery. This trial tests the Personalized Perioperative Analgesia Platform (PPAP) to tailor pain treatment for each child undergoing spinal fusion surgery, potentially reducing the need for opioids and their side effects. By examining genes that affect drug metabolism, the PPAP can more accurately adjust doses of pain medications such as methadone and oxycodone. Early evidence suggests this personalized method can lead to improved pain control and fewer complications. Although this approach is new, it holds promising benefits for children undergoing spinal fusion surgery. ^{1 3 4 6 7}

Who Is on the Research Team?

Senthilkumar Sadhasivam, MD, MPH

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for children aged 10 to nearly 18, in good to moderate health (ASA status 1-3), who will need opioids during and after a specific back surgery called Posterior-Lateral Spinal Fusion. They can't join if they have serious illnesses, already suffer from severe pain before the operation, or use/misuse opioids beforehand.

Inclusion Criteria

I was prescribed opioids when I was discharged.

I am between 10 and 17 years old.

I am currently receiving opioids in a hospital.

Exclusion Criteria

I experience severe pain before surgery.

You have a severe medical condition.

You have been using or misusing opioids before your surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative

Preoperative CYP2D6 genotyping and collection of pharmacogenetic data

1 week

1 visit (in-person)

Surgery and Immediate Post-operative

Children undergo spine fusion surgery and immediate post-operative monitoring for opioid-adverse effects

4 days

Inpatient stay

Post-operative

Monitoring of genetic factors and personalized analgesia plan implementation

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of chronic persistent surgical pain and opioid dependence

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Personalized Perioperative Analgesia Platform (PPAP)
• Preoperative Genotyping

Trial Overview The study is developing a personalized pain management system for kids having spine fusion surgery. It involves preoperative genotyping—testing their genes—to tailor pain treatment and minimize opioid-related risks.

How Is the Trial Designed?

Group I: Children undergoing Spine Fusion Surgery Experimental Treatment 1 Intervention

This arm will include approximately 300 children undergoing spine fusion surgery 1. Pharmacokinetic (PK): collection of 10-13 serial blood samples to determine serum levels of methadone/oxycodone and its metabolites 2. 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.

Who Is Running the Clinical Trial?

Senthilkumar Sadhasivam

Lead Sponsor

Trials

5

Recruited

3,200+

Senthil Sadhasivam

Lead Sponsor

Trials

7

Recruited

4,200+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study of 93 children and adolescents aged 8 to 21 who underwent spinal fusion, patient-controlled analgesia (PCA) with morphine sulfate did not significantly reduce pain levels over the first four postoperative days, with many reporting moderate-to-severe pain.

Despite the use of PCA, patient satisfaction with pain relief was only rated as 'fair' to 'good', suggesting that effective pain management may require a combination of pharmacologic and nonpharmacologic therapies rather than relying solely on high-tech solutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Children's use of PCA following spinal fusion. Kotzer, AM., Foster, R.[2019]

Patient-controlled epidural analgesia (PCEA) provided better pain relief on the first and second postoperative days compared to patient-controlled intravenous analgesia (PCIA) after spinal fusion surgery, as indicated by lower Visual Analog Scale (VAS) scores.

However, patients using PCEA experienced a higher incidence of side effects such as pruritus and paresthesia compared to those using PCIA, suggesting a trade-off between improved pain management and increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of patient-controlled epidural analgesia and patient-controlled intravenous analgesia after spinal fusion surgery: a meta-analysis of randomized controlled trials. Tian, P., Fu, X., Li, ZJ., et al.[2018]

In a study of 72 patients undergoing spinal fusion surgery, patient-controlled epidural analgesia (PCEA) significantly reduced pain levels compared to patient-controlled IV analgesia (PCIA) throughout the recovery period.

Patients using PCEA not only experienced lower pain levels but also achieved functional milestones, like turning in bed, faster and reported higher satisfaction with their pain management compared to those using PCIA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative analgesia after major spine surgery: patient-controlled epidural analgesia versus patient-controlled intravenous analgesia. Schenk, MR., Putzier, M., Kügler, B., et al.[2006]

A patient-controlled analgesia (PCA) ratio of demands to deliveries ≥1.5 can predict higher morphine requirements and greater pain scores in the first 24 hours after scoliosis surgery, based on a study of 147 adolescents.

Patients with a PCA ratio ≥1.5 also experienced more opioid-related side effects and had longer hospital stays, indicating that this ratio could be a useful tool for identifying those at risk for severe postoperative pain and complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early postoperative patient-controlled analgesia ratio predicts 24-hour morphine consumption and pain in children undergoing scoliosis surgery. Matava, CT., Crawford, MW., Pehora, C., et al.[2014]

Effective management of acute pain in orthopedic and trauma patients requires individualized approaches, especially in postoperative settings where pain can change rapidly.

Patient-controlled analgesia (PCA) enhances patient satisfaction by allowing individuals to actively participate in their pain management, and combining different analgesic classes can improve efficacy while reducing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acute pain therapy in orthopedics/trauma surgery]. Rehart, S., Henniger, M., Arndt, M.[2019]

Patient Controlled Analgesia (PCA) allows patients to manage their own pain relief by self-administering opioids, which leads to improved pain control and reduced overall opioid consumption, as patients can titrate their doses based on their individual needs.

While PCA is effective, it carries risks such as respiratory depression and potential user errors, highlighting the importance of proper programming and monitoring to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient-controlled analgesia]. Scherpereel, P.[2011]

In a study involving 10 adolescents undergoing spinal fusion for idiopathic scoliosis, patient-controlled analgesia (PCA) provided significantly better pain control compared to conventional intramuscular analgesia, as measured on a 10-point pain scale (p < 0.02).

Both PCA and intramuscular analgesia resulted in similar levels of sedation and no side effects, suggesting that PCA is a safe and effective option for postoperative pain relief in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-controlled versus conventional analgesia for postsurgical pain relief in adolescents. Walson, PD., Graves, PS., Mortensen, ME., et al.[2019]

Epidural administration of meperidine through a patient-controlled analgesia (PCA) system provided effective postoperative pain relief for patients undergoing high abdominal surgery, with no significant side effects reported.

Patients using epidural meperidine required less additional analgesia compared to those receiving subcutaneous meperidine, indicating higher satisfaction and better pain management with the epidural method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Continuous epidural perfusion with meperidine on demand for the treatment of postoperative pain]. Balust, J., Boada, J., Taurà, P., et al.[2013]

The cold pack test can effectively identify male patients who are likely to experience higher levels of postoperative pain after third molar surgery, with significant differences in pain scores observed between low and high pain tolerance groups.

Patients with low pain tolerance not only reported higher pain levels at various time points post-surgery but also consumed significantly more ibuprofen, indicating that assessing pain tolerance can help tailor analgesia strategies for better pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Predictive Value of Cold Pack Test for Pain After Third Molar Surgery. Kıraç Can, SB., Berkel, G., Can, S.[2023]

Patient-controlled analgesia (PCA) is an effective method for managing acute pain in various situations, including postoperative recovery, labor, and chronic pain, allowing patients to control their own pain relief through an infusion pump.

While PCA is generally safe and effective, common side effects include nausea, vomiting, and respiratory depression, which can be influenced by human factors like pharmacy preparation and device programming.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Update on Patient-Controlled Analgesia for Acute Postoperative Pain. Motamed, C.[2022]

The PCoA Acute patient-controlled analgesic dispenser was found to be safe and effective, with no severe adverse events reported during the study involving 70 patients across three medical centers.

Patients using the PCoA Acute took their pain medication significantly faster and reported lower pain scores compared to those receiving traditional nurse-dispensed opioids, indicating improved compliance and satisfaction with the new system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of a Novel Technology for Oral Patient-Controlled Analgesia, the PCoA&#174; Acute Device, for Hospitalized Patients with Postoperative Pain, in Pilot Feasibility Study. Wirz, S., Conrad, S., Shtrichman, R., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05367609

Personalized Perioperative Analgesia Platform (PPAP) for ... The purpose of this collaborative CTSA application is to develop an innovative perioperative precision analgesia platform (PPAP) to improve analgesia and reduce ...

2. withpower.com withpower.com/trial/phase-ppap-5-2022-12f37

Personalized Pain Management for Spinal Fusion What data supports the effectiveness of the Personalized Perioperative Analgesia Platform (PPAP) treatment for pain management in spinal fusion surgery?

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05367609

Personalized Perioperative Analgesia Platform (PPAP) for ... The purpose of this collaborative CTSA application is to develop an innovative perioperative precision analgesia platform (PPAP) to improve analgesia and ...

4. research-studies.allinforhealth.info research-studies.allinforhealth.info/us/en/listing/12398/personalized-perioperative-analgesia-platform-2/

Personalized Perioperative Analgesia Platform (PPAP) for ... The purpose of this collaborative CTSA application is to develop an innovative perioperativegesia platform (PPAP) to improve analgesia and reduce serious ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9029065/

Artificial Intelligence-Driven Prediction Modeling and Decision ... The database contains longitudinal data on spinal cord injury cases in Austria and includes clinical data with patient-related outcome measures ...

6. ctv.veeva.com ctv.veeva.com/study/personalized-perioperative-analgesia-platform-ppap-for-pediatric-spine-fusion-surgery-sirb

Personalized Perioperative Analgesia Platform (PPAP) for ... The purpose of this collaborative CTSA application is to develop an innovative perioperative precision analgesia platform (PPAP) to improve ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05367609?tab=history&a=5

Record History | ver. 5: 2023-11-09 | NCT05367609 The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome ...