Clinical trial NCT02998138: Postoperative and Chronic Pain Genetic Spine Surgery Study
Official title: A Multi-center Study of Genomic and Psychological Factors Affecting Postoperative and Chronic Pain in Children Undergoing Invasive (Spine) Surgery
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Scoliosis
Kyphosis
Kyphoscoliosis
Keywords: Chronic Pain
Pain, Postoperative
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2016-12-20
Enrollment: 880
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The investigators will recruit a total of 200 subjects over the study period to acquire the data necessary to derive a predictive model matching phenotype to genotype. They will be recruited from the population of children ages 10 to 18, inclusive, years scheduled for spinal surgical procedures.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Numeric rating scale (NRS) pain scores
timeFrame: Data will be collected for 48 hours postoperatively
measure: Occurrences of respiratory depression
timeFrame: Data will be collected for 48 hours postoperatively
measure: Occurrences of post-operative nausea/vomiting (PONV)
timeFrame: Data will be collected for 48 hours postoperatively
Secondary outcomes:
measure: Amount of morphine (or equivalent) used by patient
timeFrame: Data will be collected for 48 hours postoperative
measure: Chronic pain postoperatively
timeFrame: 2 - 6 months postoperatively
measure: Persistent pain postoperatively
timeFrame: 10 - 12 months postoperatively
measure: Opioid addiction by history on follow-up
timeFrame: 1 year postoperatively
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Hospital
state: California
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Durham
country: United States
facility: Duke Children's Hospital
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Vidya Chidambaran, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Narayanasamy S, Yang F, Ding L, Geisler K, Glynn S, Ganesh A, Sathyamoorthy M, Garcia V, Sturm P, Chidambaran V. Pediatric Pain Screening Tool: A Simple 9-Item Questionnaire Predicts Functional and Chronic Postsurgical Pain Outcomes After Major Musculoskeletal Surgeries. J Pain. 2022 Jan;23(1):98-111. doi: 10.1016/j.jpain.2021.06.014. Epub 2021 Jul 17.