<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/NCT03838107</url>
  </required_header>
  <id_info>
    <org_study_id>2018-1565</org_study_id>
    <nct_id>NCT03838107</nct_id>
  </id_info>
  <brief_title>Markers of Trajectory in Pediatric CRPS</brief_title>
  <official_title>Identifying Markers of Trajectory in Pediatric Complex Regional Pain Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chapman Family Donation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Complex Regional Pain Syndrome (CRPS) is a severe and complex chronic pain condition in&#xD;
      children. Many psychosocial factors impact its development and recovery. CRPS has a strong&#xD;
      central component, which is reflected by structural and functional changes in the brain.&#xD;
      However, the interaction between these cerebral changes and trajectory of recovery has been&#xD;
      seldom investigated to date. Furthermore, interactions between cerebral changes and&#xD;
      psychosocial factors, which might affect trajectory of recovery, are unknown. The aim of this&#xD;
      study is to identify the psychosocial factors and cerebral changes that predict the&#xD;
      trajectory of recovery from CRPS.&#xD;
&#xD;
      Children between the ages of 10 and 17 years will be enrolled with one of their parents or&#xD;
      legal guardians for this study. Three populations will be recruited: patients with CRPS&#xD;
      undergoing treatment at the Functional Independence Restoration Program (FIRST), patients&#xD;
      with CRPS undergoing treatment at the Pain Management Center and matching healthy controls.&#xD;
      Participants will undergo three sessions: the first session will be scheduled immediately&#xD;
      before or as soon as possible at the beginning of the patients' treatment; the second session&#xD;
      will take place at the end of the patients' treatment; the last session will be scheduled six&#xD;
      months post-treatment. The timing of the sessions of the healthy participants will follow a&#xD;
      schedule similar to the FIRST patients. Each session will last approximately three hours and&#xD;
      include acquisition of psychosocial, psychophysical, and brain imaging data in the child&#xD;
      participants, as well as acquisition of psychosocial data in the parent participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a basic science investigation of potential psychosocial, sensory, and brain markers&#xD;
      predicting trajectory of short-term and long-term recovery in pediatric CRPS following both&#xD;
      inpatient and outpatient treatment.&#xD;
&#xD;
      The usual inpatient treatment lasts on average three weeks and includes physical,&#xD;
      occupational, and recreational therapy, as well as psychotherapy, while patients keep their&#xD;
      regular pharmacological treatment. The usual outpatient treatment lasts on average several&#xD;
      months and includes physical therapy and psychotherapy, in addition to pharmacotherapy. For&#xD;
      both inpatients and outpatients, the primary anti-neuropathic pharmacotherapy typically&#xD;
      includes gabapentin, pregabalin, or amitriptyline, or, less frequently, duloxetine. It is&#xD;
      important to note that this study is not designed to investigate the efficacy of treatment&#xD;
      per se, instead it aims to predict trajectory during the course of treatment as usual. This&#xD;
      study is primarily mechanistic and does not include any intervention or modification of&#xD;
      treatments. Therefore, patients, who are scheduled for regular inpatient or outpatient&#xD;
      treatment of CRPS, are free to refuse to enroll without any consequences for the scheduled&#xD;
      treatment.&#xD;
&#xD;
      The investigated markers will be assessed in patients undergoing inpatient or outpatient&#xD;
      treatments. To define potentially relevant markers, measurements in patients will be compared&#xD;
      to the same measurements in healthy children. For this purpose, participants will undergo a&#xD;
      testing session just before the beginning of their treatment or as close as possible from the&#xD;
      beginning of their treatment.&#xD;
&#xD;
      To establish the influence of potential markers on short-term recovery, patients will undergo&#xD;
      an additional session upon completion of their treatment. To investigate the effect of the&#xD;
      previously defined markers on long-term recovery, patients will complete a third session at&#xD;
      six months after treatment. For comparison purposes, healthy control children will undergo&#xD;
      sessions following the same schedule as the patients. To assess the association between&#xD;
      symptoms of CRPS in children and social environment, at least one parent of each enrolled&#xD;
      child will be asked to complete three sessions following the same schedule as their child.&#xD;
&#xD;
      Each testing session will include self-reported questionnaires for the children and their&#xD;
      parents and a brain imaging session for the children.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 27, 2018</start_date>
  <completion_date type="Anticipated">August 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>changes in pain perception</measure>
    <time_frame>before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants</time_frame>
    <description>changes in ratings of spontaneous pain intensity and unpleasantness assessed on non-numerical visual analog scales, ranging from 'no pain sensation'/'not at all unpleasant' to 'most intense pain sensation imaginable'/'most unpleasant imaginable'</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in functional disability</measure>
    <time_frame>before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants</time_frame>
    <description>Changes in scores on the self-reported Functional Disability Inventory investigates disabilities associated with pain which might impact on everyday functioning of children. It includes 15 questions assessing the children's capacity to perform everyday tasks, such as doing chores, walking, or eating regular meals. Participants evaluate their capacity to perform these tasks on Likert-type scale, ranging from &quot;No Trouble&quot; to &quot;Impossible&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in functional Magnetic Resonance Imaging (fMRI) BOLD (Blood Oxygenation Level Dependent) and pCASL (pseudo-Continuous Arterio-Spin Labeling) resting-state and task-related brain signal</measure>
    <time_frame>before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants</time_frame>
    <description>fMRI BOLD and PCASL will be used to measure changes in brain activation at rest and during a multisensory task</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in fMRI BOLD and pCASL resting-state functional connectivity</measure>
    <time_frame>before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants</time_frame>
    <description>fMRI BOLD and pCASL will be used measure of changes in functional connectivity at rest</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in DTI (Diffusion Tensor Imaging) structural connectivity</measure>
    <time_frame>before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants</time_frame>
    <description>Diffusion tensor imaging will be used to measure changes in structural connectivity</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">126</enrollment>
  <condition>Complex Regional Pain Syndromes</condition>
  <arm_group>
    <arm_group_label>Inpatients</arm_group_label>
    <description>Observation and measure of trajectory of recovery in CRPS. This group will include children diagnosed with CRPS and undergoing regular therapy at the inpatient FIRST clinic at CCHMC and one of their parents or legal guardian.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Outpatients</arm_group_label>
    <description>Observation and measure of trajectory of recovery in CRPS. This group will include children diagnosed with CRPS and undergoing regular therapy at the outpatient Pain Management Center at CCHMC and one of their parents or legal guardian.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <description>For comparison purposes, healthy controls and one of their parents or legal guardian will be enrolled in this study as well.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>observation and measure of trajectory of recovery in CRPS</intervention_name>
    <description>Child participants enrolled in this study will undergo three sessions, which will include psychosocial measures, brain imaging, and quantitative sensory testing. Parent participants will also complete three sessions, which only include psychosocial measures.</description>
    <arm_group_label>Healthy Controls</arm_group_label>
    <arm_group_label>Inpatients</arm_group_label>
    <arm_group_label>Outpatients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Participants to this study may be part of one of the following groups: children diagnosed&#xD;
        with CRPS undergoing inpatient treatment at the FIRST clinic (CCHMC), children diagnosed&#xD;
        with CRPS underdoing outpatient treatment at the pain management clinic (CCHMC or&#xD;
        comparable outpatient programs), or healthy children. The investigator's groups will be&#xD;
        matched as well as possible for BMI, sex, and age. In addition, one parent will be&#xD;
        recruited with each child.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All Children:&#xD;
&#xD;
          -  Age between 10 and 17 years old&#xD;
&#xD;
          -  Fluent in English&#xD;
&#xD;
        Inpatients:&#xD;
&#xD;
          -  Diagnosis of CRPS&#xD;
&#xD;
          -  Former unsuccessful treatment for CRPS&#xD;
&#xD;
          -  Scheduled for or beginning the usual inpatient treatment for CRPS at the FIRST clinic&#xD;
             at CCHMC.&#xD;
&#xD;
        Outpatients:&#xD;
&#xD;
          -  Diagnosis of CRPS&#xD;
&#xD;
          -  Scheduled for or beginning the usual outpatient treatment for CRPS at the pain&#xD;
             management clinic&#xD;
&#xD;
        Healthy children:&#xD;
&#xD;
        - No diagnosis of chronic pain.&#xD;
&#xD;
        Parents:&#xD;
&#xD;
          -  Fluent in English&#xD;
&#xD;
          -  Child participating in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        All child participants:&#xD;
&#xD;
          -  Weight/size incompatible with MRI scanner&#xD;
&#xD;
          -  Identification of brain, neurologic, or severe psychiatric abnormalities beyond those&#xD;
             normally associated with chronic pain.&#xD;
&#xD;
          -  Documented developmental delays or impairment&#xD;
&#xD;
          -  Any MRI contra-indication, including&#xD;
&#xD;
          -  Braces, stents, clips, pace-maker or other metal implants affecting the safety of the&#xD;
             participants in the scanner and/or the quality of the images&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  claustrophobia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert C Coghill, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital, Cincinnati</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marie-Eve Hoeppli, PhD</last_name>
    <phone>(513)803-1164</phone>
    <email>marie-eve.hoeppli@cchmc.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eric Leon, BSc</last_name>
    <phone>(513) 348-0850</phone>
    <email>Eric.Leon@cchmc.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eric Leon</last_name>
      <phone>513-348-0850</phone>
      <email>eric.leon@cchmc.org</email>
    </contact>
    <contact_backup>
      <last_name>Marie-Eve Hoeppli, PhD</last_name>
      <phone>(513) 803-1164</phone>
      <email>marie-eve.hoeppli@cchmc.org</email>
    </contact_backup>
    <investigator>
      <last_name>Sara E Williams, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kenneth R Goldschneider, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>John B Rose, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 24, 2018</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>February 8, 2019</last_update_submitted>
  <last_update_submitted_qc>February 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pediatric complex regional pain syndrome</keyword>
  <keyword>fMRI</keyword>
  <keyword>psychosocial</keyword>
  <keyword>quantitative sensory testing</keyword>
  <keyword>markers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Complex Regional Pain Syndromes</mesh_term>
    <mesh_term>Reflex Sympathetic Dystrophy</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03838107/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03838107
org study id: 2018-1565
nct id: NCT03838107
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Complex Regional Pain Syndrome (CRPS) is a severe and complex chronic pain condition in
      children. Many psychosocial factors impact its development and recovery. CRPS has a strong
      central component, which is reflected by structural and functional changes in the brain.
      However, the interaction between these cerebral changes and trajectory of recovery has been
      seldom investigated to date. Furthermore, interactions between cerebral changes and
      psychosocial factors, which might affect trajectory of recovery, are unknown. The aim of this
      study is to identify the psychosocial factors and cerebral changes that predict the
      trajectory of recovery from CRPS.

      Children between the ages of 10 and 17 years will be enrolled with one of their parents or
      legal guardians for this study. Three populations will be recruited: patients with CRPS
      undergoing treatment at the Functional Independence Restoration Program (FIRST), patients
      with CRPS undergoing treatment at the Pain Management Center and matching healthy controls.
      Participants will undergo three sessions: the first session will be scheduled immediately
      before or as soon as possible at the beginning of the patients' treatment; the second session
      will take place at the end of the patients' treatment; the last session will be scheduled six
      months post-treatment. The timing of the sessions of the healthy participants will follow a
      schedule similar to the FIRST patients. Each session will last approximately three hours and
      include acquisition of psychosocial, psychophysical, and brain imaging data in the child
      participants, as well as acquisition of psychosocial data in the parent participants.
This is a basic science investigation of potential psychosocial, sensory, and brain markers
      predicting trajectory of short-term and long-term recovery in pediatric CRPS following both
      inpatient and outpatient treatment.

      The usual inpatient treatment lasts on average three weeks and includes physical,
      occupational, and recreational therapy, as well as psychotherapy, while patients keep their
      regular pharmacological treatment. The usual outpatient treatment lasts on average several
      months and includes physical therapy and psychotherapy, in addition to pharmacotherapy. For
      both inpatients and outpatients, the primary anti-neuropathic pharmacotherapy typically
      includes gabapentin, pregabalin, or amitriptyline, or, less frequently, duloxetine. It is
      important to note that this study is not designed to investigate the efficacy of treatment
      per se, instead it aims to predict trajectory during the course of treatment as usual. This
      study is primarily mechanistic and does not include any intervention or modification of
      treatments. Therefore, patients, who are scheduled for regular inpatient or outpatient
      treatment of CRPS, are free to refuse to enroll without any consequences for the scheduled
      treatment.

      The investigated markers will be assessed in patients undergoing inpatient or outpatient
      treatments. To define potentially relevant markers, measurements in patients will be compared
      to the same measurements in healthy children. For this purpose, participants will undergo a
      testing session just before the beginning of their treatment or as close as possible from the
      beginning of their treatment.

      To establish the influence of potential markers on short-term recovery, patients will undergo
      an additional session upon completion of their treatment. To investigate the effect of the
      previously defined markers on long-term recovery, patients will complete a third session at
      six months after treatment. For comparison purposes, healthy control children will undergo
      sessions following the same schedule as the patients. To assess the association between
      symptoms of CRPS in children and social environment, at least one parent of each enrolled
      child will be asked to complete three sessions following the same schedule as their child.

      Each testing session will include self-reported questionnaires for the children and their
      parents and a brain imaging session for the children.
observational model: Case-Control
time perspective: Prospective
measure: changes in pain perception
time frame: before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants
description: changes in ratings of spontaneous pain intensity and unpleasantness assessed on non-numerical visual analog scales, ranging from 'no pain sensation'/'not at all unpleasant' to 'most intense pain sensation imaginable'/'most unpleasant imaginable'
measure: Changes in functional disability
time frame: before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants
description: Changes in scores on the self-reported Functional Disability Inventory investigates disabilities associated with pain which might impact on everyday functioning of children. It includes 15 questions assessing the children's capacity to perform everyday tasks, such as doing chores, walking, or eating regular meals. Participants evaluate their capacity to perform these tasks on Likert-type scale, ranging from "No Trouble" to "Impossible".
measure: Changes in functional Magnetic Resonance Imaging (fMRI) BOLD (Blood Oxygenation Level Dependent) and pCASL (pseudo-Continuous Arterio-Spin Labeling) resting-state and task-related brain signal
time frame: before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants
description: fMRI BOLD and PCASL will be used to measure changes in brain activation at rest and during a multisensory task
measure: changes in fMRI BOLD and pCASL resting-state functional connectivity
time frame: before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants
description: fMRI BOLD and pCASL will be used measure of changes in functional connectivity at rest
measure: changes in DTI (Diffusion Tensor Imaging) structural connectivity
time frame: before treatment, at the end of the treatment (an average of 4 weeks for inpatients and 3 months for outpatients after session 1), and 6-month post treatment for patients; 1 month after session 1 and 6 months after session 2 for healthy participants
description: Diffusion tensor imaging will be used to measure changes in structural connectivity
arm group label: Inpatients
description: Observation and measure of trajectory of recovery in CRPS. This group will include children diagnosed with CRPS and undergoing regular therapy at the inpatient FIRST clinic at CCHMC and one of their parents or legal guardian.
arm group label: Outpatients
description: Observation and measure of trajectory of recovery in CRPS. This group will include children diagnosed with CRPS and undergoing regular therapy at the outpatient Pain Management Center at CCHMC and one of their parents or legal guardian.
arm group label: Healthy Controls
description: For comparison purposes, healthy controls and one of their parents or legal guardian will be enrolled in this study as well.
intervention type: Behavioral
intervention name: observation and measure of trajectory of recovery in CRPS
description: Child participants enrolled in this study will undergo three sessions, which will include psychosocial measures, brain imaging, and quantitative sensory testing. Parent participants will also complete three sessions, which only include psychosocial measures.
arm group label: Healthy Controls
arm group label: Inpatients
arm group label: Outpatients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 10 Years
maximum age: 17 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Robert C Coghill, PhD
role: Principal Investigator
affiliation: Children's Hospital, Cincinnati
last name: Marie-Eve Hoeppli, PhD
phone: (513)803-1164
email: marie-eve.hoeppli@cchmc.org
last name: Eric Leon, BSc
phone: (513) 348-0850
email: Eric.Leon@cchmc.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Complex Regional Pain Syndromes
mesh term: Reflex Sympathetic Dystrophy
mesh term: Syndrome
sharing ipd: No
provided document: 