<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/NCT02219373</url>
  </required_header>
  <id_info>
    <org_study_id>P00008001</org_study_id>
    <nct_id>NCT02219373</nct_id>
  </id_info>
  <brief_title>Gabapentin and Oxcarbazepine for Chronic Neuropathic Pain in Children and Adolescents: A Clinical Effectiveness Study</brief_title>
  <official_title>Gabapentin and Oxcarbazepine for Chronic Neuropathic Pain in Children and Adolescents: A Double-Blind, Randomized Clinical Effectiveness Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boston Children's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Given the widespread use of anticonvulsants in the pediatric chronic pain population and the&#xD;
      absence of scientific data supporting their use, the investigators propose a randomized,&#xD;
      double blind, two group parallel design in which a broad group of children and adolescents&#xD;
      with chronic neuropathic pain would be randomized to receive either Gabapentin or&#xD;
      Oxcarbazepine.&#xD;
&#xD;
      The Primary Aim of the Study is to assess the frequencies of successful treatment of&#xD;
      pediatric patients with neuropathic pain treated with either Gabapentin or Oxcarbazepine.&#xD;
&#xD;
      The Primary Hypotheses are as follows:&#xD;
&#xD;
      Hypothesis I: Both Gabapentin and Oxcarbazepine will result in significant reduction in pain&#xD;
      scores when compared to each patient's baseline.&#xD;
&#xD;
      Hypothesis II: Patients who continue on active drug (Gabapentin or Oxcarbazepine) during the&#xD;
      second phase of the trial will report greater pain reduction relative to baseline than&#xD;
      patients who are randomized onto placebo at this randomization point.&#xD;
&#xD;
      Secondary Aims of the Study are to compare groups treated initially with Gabapentin or&#xD;
      Oxcarbazepine with regard to reduction in pain scores (both at rest and with evoked&#xD;
      maneuvers), functional disability scores, tolerability, and measures of mood and cognitive&#xD;
      functioning.&#xD;
&#xD;
      Secondary Hypotheses are that Gabapentin and Oxcarbazepine differ in their effects on:&#xD;
&#xD;
        1. Pain scores at rest and with evoked maneuvers&#xD;
&#xD;
        2. Functional disability scores&#xD;
&#xD;
        3. Tolerability (frequencies of side-effects)&#xD;
&#xD;
        4. Depression and anxiety scales&#xD;
&#xD;
        5. Neuropsychological measures of cognitive processing speed, working memory, and&#xD;
           attention.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">August 2023</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>As a primary outcome, success will be defined by clinically and statistically significant within subject reductions in pain scores</measure>
    <time_frame>0 (baseline), 2, 4, 6, 8 weeks (post-assignment of intervention)</time_frame>
    <description>2 point reduction in average daily pain scores&#xD;
30% reduction relative to baseline&#xD;
Global overall impression of strong benefit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Scores at rest and evoked maneuvers</measure>
    <time_frame>0 (baseline) and 4 and 8 weeks (post assignment of intervention)</time_frame>
    <description>The investigators will assess pain scores at rest and with evoked maneuvers through exam and quantitative sensory test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of side effects- Tolerability</measure>
    <time_frame>1, 2, 4, 6, 8 weeks (post assignment of intervention)</time_frame>
    <description>Common side effects include headaches and feeling sleepier in the morning and having less energy. Side effects that can occur, but are not common, include gastrointestinal side effects (upset stomach or throwing up, diarrhea or constipation, and weight gain), feeling lightheaded, having blurred eyesight, shakiness or changes in balance.&#xD;
Very rarely, patients taking these medicines may experience memory problems, sadness, nervousness, and Serious Adverse Events (SAEs).&#xD;
Routine laboratory testing will be conducted as part of the safety profile assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Disability Scores</measure>
    <time_frame>0 (baseline), 4, and 8 weeks (post-assignment of intervention)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Side effects- Depression and Anxiety</measure>
    <time_frame>Baseline, Week 4 and 8 (post assignment of the intervention)</time_frame>
    <description>As both study medicines may be associated with mood changes and as pain itself sometimes is co-morbid with anxiety and depression, the investigators will perform self-report measures of anxiety and depression (Children's Depressive Inventory and The Revised Children's Manifest Anxiety Scale) pre and post-assigment of the intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Side Effects- Neuropsychological Measures</measure>
    <time_frame>Baseline, weeks 4 and 8 (post-assignment of the intervention).</time_frame>
    <description>Both study medicines may be associated with the emergence of cognitive side effects to include difficulties with concentration and cognitive slowing. The investigators will assess for cognitive processing speed, working memory and attention difficulties during the course of treatment using the NIH toobox Cognitive Battery.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Pediatric Chronic Neuropathic Pain</condition>
  <arm_group>
    <arm_group_label>Gabapentin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Oxcarbazepine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients taking placebo will have placebo dose escalated using similar frequency, periods of time, and volumes as those for the active drugs.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gabapentin</intervention_name>
    <description>Patients will be randomized to receive either Gabapentin or Oxcarbazepine. The assignment of the medications will be randomized and blinded to both the study investigators and the patient. If patients exhibit &gt;30% pain reduction on receiving the medication evaluated after 4 weeks, then they may continue to receive either the same medication or placebo. If patients exhibit &lt;30% pain reduction, the patient will crossover to the other medication option in the protocol.</description>
    <arm_group_label>Gabapentin</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxcarbazepine</intervention_name>
    <description>Patients will be randomized to receive either Gabapentin or Oxcarbazepine. The assignment of the medications will be randomized and blinded to both the study investigators and the patient. If patients exhibit &gt;30% pain reduction on receiving the medication evaluated after 4 weeks, then they may continue to receive either the same medication or placebo. If patients exhibit &lt;30% pain reduction, the patient will crossover to the other medication option in the protocol.</description>
    <arm_group_label>Oxcarbazepine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patients taking placebo will have placebo dose escalated using similar frequency, periods of time, and volumes as those for the active drugs.</description>
    <arm_group_label>Gabapentin</arm_group_label>
    <arm_group_label>Oxcarbazepine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients between the ages of 8 and 18 at the time of the study with history of chronic&#xD;
             (lasting ≥ 4 weeks) neuropathic pain that includes a known injury to a peripheral&#xD;
             nerve and/or a pattern of pain responses that includes allodynia, burning,&#xD;
             paresthesias or dysesthesias will be included in this study, provided that informed&#xD;
             consent has been given by parents.&#xD;
&#xD;
          2. Patient's whose pain rates between moderate to severe at the time of inclusion&#xD;
             (ranging from 4-10 in a numeric pain rating scale)&#xD;
&#xD;
          3. Eligible diagnoses include Complex Regional Pain Syndrome, Fibromyalgia, Lumbar&#xD;
             Radiculopathy, Spinal Cord Injury, Erythromelalgia, Small Fiber Neuropathies,&#xD;
             Traumatic or Post-surgical Peripheral Nerve or Plexus Injuries, and Extremity Pain&#xD;
             with severe pain to light touch (allodynia).&#xD;
&#xD;
          4. Child has age-appropriate spoken and written knowledge of English.&#xD;
&#xD;
          5. Parent may be able to utilize an interpreter if need be.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unstable psychiatric illness (suicidal ideation, disorganized behavior)&#xD;
&#xD;
          2. Uncontrolled Seizure disorder&#xD;
&#xD;
          3. Chronic Headaches only&#xD;
&#xD;
          4. Abdominal Pain only&#xD;
&#xD;
          5. Prior experience with anticonvulsants for pain treatment.&#xD;
&#xD;
          6. Patients with Syndrome of Inappropriate Secretion of Antidiuretic Hormone&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Monique Ribeiro, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston Children's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Monique Ribeiro, MD</last_name>
    <phone>(617) 355-7040</phone>
    <email>Monique.Ribeiro@childrens.harvard.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kimberly Lobo, MPH</last_name>
    <phone>(857) 218-3556</phone>
    <email>Kimberly.Lobo@childrens.harvard.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <investigator>
      <last_name>Monique Ribeiro, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 8, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Boston Children's Hospital</investigator_affiliation>
    <investigator_full_name>Monique Ribeiro</investigator_full_name>
    <investigator_title>Physician</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxcarbazepine</mesh_term>
    <mesh_term>Gabapentin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02219373
org study id: P00008001
nct id: NCT02219373
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Given the widespread use of anticonvulsants in the pediatric chronic pain population and the
      absence of scientific data supporting their use, the investigators propose a randomized,
      double blind, two group parallel design in which a broad group of children and adolescents
      with chronic neuropathic pain would be randomized to receive either Gabapentin or
      Oxcarbazepine.

      The Primary Aim of the Study is to assess the frequencies of successful treatment of
      pediatric patients with neuropathic pain treated with either Gabapentin or Oxcarbazepine.

      The Primary Hypotheses are as follows:

      Hypothesis I: Both Gabapentin and Oxcarbazepine will result in significant reduction in pain
      scores when compared to each patient's baseline.

      Hypothesis II: Patients who continue on active drug (Gabapentin or Oxcarbazepine) during the
      second phase of the trial will report greater pain reduction relative to baseline than
      patients who are randomized onto placebo at this randomization point.

      Secondary Aims of the Study are to compare groups treated initially with Gabapentin or
      Oxcarbazepine with regard to reduction in pain scores (both at rest and with evoked
      maneuvers), functional disability scores, tolerability, and measures of mood and cognitive
      functioning.

      Secondary Hypotheses are that Gabapentin and Oxcarbazepine differ in their effects on:

        1. Pain scores at rest and with evoked maneuvers

        2. Functional disability scores

        3. Tolerability (frequencies of side-effects)

        4. Depression and anxiety scales

        5. Neuropsychological measures of cognitive processing speed, working memory, and
           attention.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: As a primary outcome, success will be defined by clinically and statistically significant within subject reductions in pain scores
time frame: 0 (baseline), 2, 4, 6, 8 weeks (post-assignment of intervention)
description: 2 point reduction in average daily pain scores
30% reduction relative to baseline
Global overall impression of strong benefit.
measure: Pain Scores at rest and evoked maneuvers
time frame: 0 (baseline) and 4 and 8 weeks (post assignment of intervention)
description: The investigators will assess pain scores at rest and with evoked maneuvers through exam and quantitative sensory test.
measure: Frequency of side effects- Tolerability
time frame: 1, 2, 4, 6, 8 weeks (post assignment of intervention)
description: Common side effects include headaches and feeling sleepier in the morning and having less energy. Side effects that can occur, but are not common, include gastrointestinal side effects (upset stomach or throwing up, diarrhea or constipation, and weight gain), feeling lightheaded, having blurred eyesight, shakiness or changes in balance.
Very rarely, patients taking these medicines may experience memory problems, sadness, nervousness, and Serious Adverse Events (SAEs).
Routine laboratory testing will be conducted as part of the safety profile assessment.
measure: Functional Disability Scores
time frame: 0 (baseline), 4, and 8 weeks (post-assignment of intervention)
measure: Frequency of Side effects- Depression and Anxiety
time frame: Baseline, Week 4 and 8 (post assignment of the intervention)
description: As both study medicines may be associated with mood changes and as pain itself sometimes is co-morbid with anxiety and depression, the investigators will perform self-report measures of anxiety and depression (Children's Depressive Inventory and The Revised Children's Manifest Anxiety Scale) pre and post-assigment of the intervention.
measure: Frequency of Side Effects- Neuropsychological Measures
time frame: Baseline, weeks 4 and 8 (post-assignment of the intervention).
description: Both study medicines may be associated with the emergence of cognitive side effects to include difficulties with concentration and cognitive slowing. The investigators will assess for cognitive processing speed, working memory and attention difficulties during the course of treatment using the NIH toobox Cognitive Battery.
arm group label: Gabapentin
arm group type: Experimental
arm group label: Oxcarbazepine
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients taking placebo will have placebo dose escalated using similar frequency, periods of time, and volumes as those for the active drugs.
intervention type: Drug
intervention name: Gabapentin
description: Patients will be randomized to receive either Gabapentin or Oxcarbazepine. The assignment of the medications will be randomized and blinded to both the study investigators and the patient. If patients exhibit >30% pain reduction on receiving the medication evaluated after 4 weeks, then they may continue to receive either the same medication or placebo. If patients exhibit <30% pain reduction, the patient will crossover to the other medication option in the protocol.
arm group label: Gabapentin
arm group label: Placebo
intervention type: Drug
intervention name: Oxcarbazepine
description: Patients will be randomized to receive either Gabapentin or Oxcarbazepine. The assignment of the medications will be randomized and blinded to both the study investigators and the patient. If patients exhibit >30% pain reduction on receiving the medication evaluated after 4 weeks, then they may continue to receive either the same medication or placebo. If patients exhibit <30% pain reduction, the patient will crossover to the other medication option in the protocol.
arm group label: Oxcarbazepine
arm group label: Placebo
intervention type: Other
intervention name: Placebo
description: Patients taking placebo will have placebo dose escalated using similar frequency, periods of time, and volumes as those for the active drugs.
arm group label: Gabapentin
arm group label: Oxcarbazepine
arm group label: Placebo
criteria: 
gender: All
minimum age: 8 Years
maximum age: 18 Years
healthy volunteers: No
last name: Monique Ribeiro, MD
role: Principal Investigator
affiliation: Boston Children's Hospital
last name: Monique Ribeiro, MD
phone: (617) 355-7040
email: Monique.Ribeiro@childrens.harvard.edu
last name: Kimberly Lobo, MPH
phone: (857) 218-3556
email: Kimberly.Lobo@childrens.harvard.edu
facility: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Boston Children's Hospital
investigator full name: Monique Ribeiro
investigator title: Physician
mesh term: Neuralgia
mesh term: Oxcarbazepine
mesh term: Gabapentin