Postoperative and Chronic Pain Genetic Spine Surgery Study

Active, not recruiting

• Conditions: Scoliosis; Kyphosis; Kyphoscoliosis

• Registration Number: NCT02998138
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

This will be an open label, prospective study to determine the association between specific genotypes, epigenetics and behavioral factors, with the phenotypes, defined by pain perception, postoperative pain, analgesic and side effect responses to perioperative opioids, chronic postoperative pain and gene expression in adolescents following major spine surgery.

Detailed Description

Safe and effective analgesia is an important unmet medical need in children. Despite efforts to promote non-pharmacologic interventions, drug treatment remains the standard of care for children experiencing severe pain following surgery. Inadequate pain relief after invasive surgery, and side effects from analgesics such as morphine occur frequently in up to 50% of children. A study of patient controlled analgesia (PCA) morphine use after spine surgery in adolescents observed a 45% incidence of postoperative nausea and vomiting and 7% incidence of respiratory depression. Presently, evidence-based dosing guidelines for opioid therapy have not been ascertained in the pediatric patient population, and remains a trial and error method. Despite aggressive pain management after spine surgery, findings showed that neither children's pain nor their analgesic use diminished significantly over time. As such, there is a critical knowledge gap in the medical literature that significantly impacts the pediatric pain management. Moreover, chronic postsurgical pain (CPSP, defined as pain attributable to the surgical procedure lasting for more than 2 months after surgery critically impacts 13-30% of children having surgery, and leads to chronic pain as adults imposing extraordinary annual costs on the health care system ($560-635 billion). It has been recently shown that pain unpleasantness predicts the transition from acute to moderate/severe persistent post-surgical pain, whereas anxiety sensitivity predicts the maintenance of moderate/severe post-surgical pain from 6 to 12 months after surgery. Spine fusion in adolescents is a particularly painful surgery with 15% incidence of pain even 5 years after surgery, and hence will serve as a good surgical model to evaluate the behavioral and genetic predictors of chronic postoperative pain. In recognition of this therapeutic challenge the investigators plan to evaluate the determinants of inter-individual differences in opioid analgesic responsiveness, adverse effects, pain perception and predictors of chronic postoperative pain in children.

Study Timeline

• Study First Submitted: 2016-03-07
• Study Start: 2016-12
• Study First Submitted QC: 2016-12-15
• Study First Posted: 2016-12-20
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-20
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 880

Inclusion Criteria

1. Children aged 10 to 18, inclusive, years of age
2. Diagnosis of Idiopathic scoliosis, kyphosis and/or kyphoscoliosis
3. Scheduled for spine fusion.

Exclusion Criteria

1. Patients on chronic pain medication (opioid use over 6 months prior to surgery)
2. Pregnant or breastfeeding females.
3. Children with a history of or active renal or liver disease.
4. Non-English speaking patients.
5. Developmental delay
6. Body Mass Index ≥ 30
7. Currently taking tricyclic, selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI) class of medications (within the last month)
8. Cardiac conditions including, but not limited to, cyanotic heart disease, Hypoplastic Left Ventricle, arrhythmia, hypertension with ongoing treatment, Kawasaki Disease, cardiomyopathies. Patients with asymptomatic valvular lesions or defects may be included.
9. Severe lung disease such as cystic fibrosis, pulmonary fibrosis, pneumonia within the last month
10. History of seizures currently treated on medication (patients off medication and seizure free for greater than one year may be included)
11. Other known genetic diseases including but not limited to Ehlers Danlos, Downs' etc.
12. History of Obstructive sleep apnea by history (pauses during sleep, significant snoring, use of CPAP)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Occurrences of respiratory depression	Data will be collected for 48 hours postoperatively	Respiratory rate (RR) \<10 on POD 1 and 2
Occurrences of post-operative nausea/vomiting (PONV)	Data will be collected for 48 hours postoperatively
Numeric rating scale (NRS) pain scores	Data will be collected for 48 hours postoperatively

Secondary Outcome Measures

Name	Time	Method
Persistent pain postoperatively	10 - 12 months postoperatively	Participants will complete questionnaires regarding pain since surgery was completed
Opioid addiction by history on follow-up	1 year postoperatively
Amount of morphine (or equivalent) used by patient	Data will be collected for 48 hours postoperative
Chronic pain postoperatively	2 - 6 months postoperatively	Participants will complete questionnaires regarding pain since surgery was completed

Trial Locations

Locations (5)

Duke Children's Hospital; 🇺🇸 Durham, North Carolina, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Stanford University Hospital; 🇺🇸 Stanford, California, United States