<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02998138</url>
  </required_header>
  <id_info>
    <org_study_id>2015-8339</org_study_id>
    <secondary_id>2015-8633</secondary_id>
    <nct_id>NCT02998138</nct_id>
  </id_info>
  <brief_title>Postoperative and Chronic Pain Genetic Spine Surgery Study</brief_title>
  <official_title>A Multi-center Study of Genomic and Psychological Factors Affecting Postoperative and Chronic Pain in Children Undergoing Invasive (Spine) Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be an open label, prospective study to determine the association between specific&#xD;
      genotypes, epigenetics and behavioral factors, with the phenotypes, defined by pain&#xD;
      perception, postoperative pain, analgesic and side effect responses to perioperative opioids,&#xD;
      chronic postoperative pain and gene expression in adolescents following major spine surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Safe and effective analgesia is an important unmet medical need in children. Despite efforts&#xD;
      to promote non-pharmacologic interventions, drug treatment remains the standard of care for&#xD;
      children experiencing severe pain following surgery. Inadequate pain relief after invasive&#xD;
      surgery, and side effects from analgesics such as morphine occur frequently in up to 50% of&#xD;
      children. A study of patient controlled analgesia (PCA) morphine use after spine surgery in&#xD;
      adolescents observed a 45% incidence of postoperative nausea and vomiting and 7% incidence of&#xD;
      respiratory depression. Presently, evidence-based dosing guidelines for opioid therapy have&#xD;
      not been ascertained in the pediatric patient population, and remains a trial and error&#xD;
      method. Despite aggressive pain management after spine surgery, findings showed that neither&#xD;
      children's pain nor their analgesic use diminished significantly over time. As such, there is&#xD;
      a critical knowledge gap in the medical literature that significantly impacts the pediatric&#xD;
      pain management. Moreover, chronic postsurgical pain (CPSP, defined as pain attributable to&#xD;
      the surgical procedure lasting for more than 2 months after surgery critically impacts 13-30%&#xD;
      of children having surgery, and leads to chronic pain as adults imposing extraordinary annual&#xD;
      costs on the health care system ($560-635 billion). It has been recently shown that pain&#xD;
      unpleasantness predicts the transition from acute to moderate/severe persistent post-surgical&#xD;
      pain, whereas anxiety sensitivity predicts the maintenance of moderate/severe post-surgical&#xD;
      pain from 6 to 12 months after surgery. Spine fusion in adolescents is a particularly painful&#xD;
      surgery with 15% incidence of pain even 5 years after surgery, and hence will serve as a good&#xD;
      surgical model to evaluate the behavioral and genetic predictors of chronic postoperative&#xD;
      pain. In recognition of this therapeutic challenge the investigators plan to evaluate the&#xD;
      determinants of inter-individual differences in opioid analgesic responsiveness, adverse&#xD;
      effects, pain perception and predictors of chronic postoperative pain in children.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Numeric rating scale (NRS) pain scores</measure>
    <time_frame>Data will be collected for 48 hours postoperatively</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrences of respiratory depression</measure>
    <time_frame>Data will be collected for 48 hours postoperatively</time_frame>
    <description>Respiratory rate (RR) &lt;10 on POD 1 and 2</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrences of post-operative nausea/vomiting (PONV)</measure>
    <time_frame>Data will be collected for 48 hours postoperatively</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Amount of morphine (or equivalent) used by patient</measure>
    <time_frame>Data will be collected for 48 hours postoperative</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic pain postoperatively</measure>
    <time_frame>2 - 6 months postoperatively</time_frame>
    <description>Participants will complete questionnaires regarding pain since surgery was completed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistent pain postoperatively</measure>
    <time_frame>10 - 12 months postoperatively</time_frame>
    <description>Participants will complete questionnaires regarding pain since surgery was completed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Opioid addiction by history on follow-up</measure>
    <time_frame>1 year postoperatively</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">880</enrollment>
  <condition>Scoliosis</condition>
  <condition>Kyphosis</condition>
  <condition>Kyphoscoliosis</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples will be analyzed for a defined set of SNPs using PCR (TaqMan, ABI)/and Omni5M&#xD;
      GWAS chip testing. DNA will be isolated from blood samples and also be used for&#xD;
      pyrosequencing studies to obtain DNA methylation information for a specified set of genes or&#xD;
      use of the MethylationEPIC array. The SNP sets were chosen using the adult studies cited in&#xD;
      the Background and Significance section as evidence of potential importance. Given that the&#xD;
      pain response in children and adolescents may involve a novel or different set of SNPs and&#xD;
      additional SNPs of the above genes, the DNA samples gathered will be held for future&#xD;
      analysis.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The investigators will recruit a total of 200 subjects over the study period to acquire the&#xD;
        data necessary to derive a predictive model matching phenotype to genotype. They will be&#xD;
        recruited from the population of children ages 10 to 18, inclusive, years scheduled for&#xD;
        spinal surgical procedures.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Children aged 10 to 18, inclusive, years of age&#xD;
&#xD;
          2. Diagnosis of Idiopathic scoliosis, kyphosis and/or kyphoscoliosis&#xD;
&#xD;
          3. Scheduled for spine fusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients on chronic pain medication (opioid use over 6 months prior to surgery)&#xD;
&#xD;
          2. Pregnant or breastfeeding females.&#xD;
&#xD;
          3. Children with a history of or active renal or liver disease.&#xD;
&#xD;
          4. Non-English speaking patients.&#xD;
&#xD;
          5. Developmental delay&#xD;
&#xD;
          6. Body Mass Index ≥ 30&#xD;
&#xD;
          7. Currently taking tricyclic, selective serotonin reuptake inhibitor (SSRI),&#xD;
             serotonin-norepinephrine reuptake inhibitor (SNRI) class of medications (within the&#xD;
             last month)&#xD;
&#xD;
          8. Cardiac conditions including, but not limited to, cyanotic heart disease, Hypoplastic&#xD;
             Left Ventricle, arrhythmia, hypertension with ongoing treatment, Kawasaki Disease,&#xD;
             cardiomyopathies. Patients with asymptomatic valvular lesions or defects may be&#xD;
             included.&#xD;
&#xD;
          9. Severe lung disease such as cystic fibrosis, pulmonary fibrosis, pneumonia within the&#xD;
             last month&#xD;
&#xD;
         10. History of seizures currently treated on medication (patients off medication and&#xD;
             seizure free for greater than one year may be included)&#xD;
&#xD;
         11. Other known genetic diseases including but not limited to Ehlers Danlos, Downs' etc.&#xD;
&#xD;
         12. History of Obstructive sleep apnea by history (pauses during sleep, significant&#xD;
             snoring, use of CPAP)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vidya Chidambaran, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University Hospital</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Children's Hospital</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>March 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic Pain</keyword>
  <keyword>Pain, Postoperative</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scoliosis</mesh_term>
    <mesh_term>Kyphosis</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02998138
org study id: 2015-8339
secondary id: 2015-8633
nct id: NCT02998138
lead sponsor: 
has dmc: No
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.
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.
observational model: Cohort
time perspective: Prospective
measure: Numeric rating scale (NRS) pain scores
time frame: Data will be collected for 48 hours postoperatively
measure: Occurrences of respiratory depression
time frame: Data will be collected for 48 hours postoperatively
description: Respiratory rate (RR) <10 on POD 1 and 2
measure: Occurrences of post-operative nausea/vomiting (PONV)
time frame: Data will be collected for 48 hours postoperatively
measure: Amount of morphine (or equivalent) used by patient
time frame: Data will be collected for 48 hours postoperative
measure: Chronic pain postoperatively
time frame: 2 - 6 months postoperatively
description: Participants will complete questionnaires regarding pain since surgery was completed
measure: Persistent pain postoperatively
time frame: 10 - 12 months postoperatively
description: Participants will complete questionnaires regarding pain since surgery was completed
measure: Opioid addiction by history on follow-up
time frame: 1 year postoperatively
Blood samples will be analyzed for a defined set of SNPs using PCR (TaqMan, ABI)/and Omni5M
      GWAS chip testing. DNA will be isolated from blood samples and also be used for
      pyrosequencing studies to obtain DNA methylation information for a specified set of genes or
      use of the MethylationEPIC array. The SNP sets were chosen using the adult studies cited in
      the Background and Significance section as evidence of potential importance. Given that the
      pain response in children and adolescents may involve a novel or different set of SNPs and
      additional SNPs of the above genes, the DNA samples gathered will be held for future
      analysis.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 10 Years
maximum age: 18 Years
healthy volunteers: No
last name: Vidya Chidambaran, MD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Scoliosis
mesh term: Kyphosis
mesh term: Chronic Pain
sharing ipd: No