Postoperative and Chronic Pain Genetic Spine Surgery Study

Scoliosis Clinical Trial

Official title:

A Multi-center Study of Genomic and Psychological Factors Affecting Postoperative and Chronic Pain in Children Undergoing Invasive (Spine) Surgery

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02998138
• Other study ID #: 2015-8339
• Secondary ID: 2015-8633
• Status: Enrolling by invitation
• Start date: December 2016
• Est. completion date: December 2026

Study information

• Verified date: July 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 880
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Pain
• Kyphoscoliosis
• Kyphosis
• Scoliosis

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Duke Children's Hospital	Durham	North Carolina
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

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numeric rating scale (NRS) pain scores		Data will be collected for 48 hours postoperatively
Primary	Occurrences of respiratory depression	Respiratory rate (RR) <10 on POD 1 and 2	Data will be collected for 48 hours postoperatively
Primary	Occurrences of post-operative nausea/vomiting (PONV)		Data will be collected for 48 hours postoperatively
Secondary	Amount of morphine (or equivalent) used by patient		Data will be collected for 48 hours postoperative
Secondary	Chronic pain postoperatively	Participants will complete questionnaires regarding pain since surgery was completed	2 - 6 months postoperatively
Secondary	Persistent pain postoperatively	Participants will complete questionnaires regarding pain since surgery was completed	10 - 12 months postoperatively
Secondary	Opioid addiction by history on follow-up		1 year postoperatively