<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/NCT04483401</url>
  </required_header>
  <id_info>
    <org_study_id>H16-00358</org_study_id>
    <nct_id>NCT04483401</nct_id>
  </id_info>
  <brief_title>Premie DCD Imaging Intervention Study</brief_title>
  <official_title>Developmental Coordination Disorder in Preterm Children: Examining Brain Changes With CO-OP Intervention</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of British Columbia</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>
      This study will leverage a current longitudinal study of brain development in preterm&#xD;
      children. In the Miller/Grunau Trajectories study, preterm children are returning for&#xD;
      follow-up at 8-9 years. At this appointment, children undergo MRI and neurodevelopmental&#xD;
      testing. Children who are identified with DCD at this appointment will be invited to&#xD;
      participate in this intervention study. Participants will have a 2nd MRI 12 weeks after the&#xD;
      first scan. They will then receive 12 weekly sessions with an occupational therapist,&#xD;
      followed by a third MRI.&#xD;
&#xD;
      Children with DCD who were born very preterm (&lt;32 weeks gestational age) who are not part of&#xD;
      the Miller/Grunau study are also eligible to participate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      RATIONALE Developmental coordination disorder (DCD) is one of the most common disorders in&#xD;
      children (Wann, 2007), affecting 5-6% of the school-age population; this is &gt; 400,000&#xD;
      children in Canada, or 1-2 children in every classroom (American Psychiatric Association,&#xD;
      2013; Statistics Canada, 2013). Compared with children born at term, preterm children (born&#xD;
      2-4 months early) are 6-8 times more likely to develop DCD (Edwards…Zwicker, 2011). DCD&#xD;
      significantly interferes with a child's ability to learn motor skills and to perform everyday&#xD;
      activities, such as getting dressed, tying shoelaces, using a knife and fork, printing,&#xD;
      playing sports, or riding a bicycle. While it was once believed that children would outgrow&#xD;
      this condition, longitudinal research has shown that functional difficulties can persist into&#xD;
      adolescence and adulthood (Cantell, Smyth, &amp; Ahonen, 2003; Cousins &amp; Smyth, 2003).&#xD;
      Furthermore, secondary psychosocial difficulties often develop, including poor self-esteem,&#xD;
      depression, anxiety, problems with peers, loneliness, and decreased participation in physical&#xD;
      and social activities (Zwicker, Harris, &amp; Klassen, 2013). Up to half of children with DCD&#xD;
      will have co-occurring attention deficit hyperactivity disorder (ADHD) (Kadesjo &amp; Gillberg,&#xD;
      1998). As a chronic health condition, DCD often interferes with an individual's function and&#xD;
      quality of life across their lifespan (Cousins &amp; Smyth, 2003; Zwicker et al., 2013)&#xD;
&#xD;
      The cause of DCD is not known, and it is under-recognized, under-diagnosed, and under-treated&#xD;
      (Blank et al., 2012). In particular, the investigators do not understand the neural basis of&#xD;
      DCD, making it difficult to understand why children with DCD struggle to learn motor skills&#xD;
      and to determine how to best intervene to optimize function.&#xD;
&#xD;
      To change the negative trajectory of children with DCD, the investigators need a better&#xD;
      understanding of the neural basis of DCD, along with further rehabilitation efforts to&#xD;
      improve outcomes. Recently, the investigators and others have conducted small neuroimaging&#xD;
      studies to begin to understand brain differences in DCD (Querne et al., 2008; Kashiwagi et&#xD;
      al., 2009, Zwicker et al., 2010, 2011, 2012b). These studies, while novel and significant in&#xD;
      advancing the field of DCD, are limited by small sample sizes. To further define the neural&#xD;
      correlates of DCD, the investigators need to perform larger studies and take advantage of new&#xD;
      neuroimaging techniques. To date, no studies have examined neural correlates of DCD in the&#xD;
      preterm population, a group that is at particularly high risk for the disorder. In addition,&#xD;
      brain imaging studies may determine whether improvements in motor function with current &quot;best&#xD;
      practice&quot; rehabilitation intervention are associated with changes in brain&#xD;
      structure/function. A greater understanding of the neural basis of DCD may result in earlier&#xD;
      diagnosis and early rehabilitation to mediate better brain development.&#xD;
&#xD;
      Currently, the investigators have a study underway that assesses whether rehabilitation&#xD;
      intervention and improved outcomes in children with DCD are associated with concurrent brain&#xD;
      changes (H14-00397). This proposed research extends this study to determine whether preterm&#xD;
      children with DCD show similar brain changes.&#xD;
&#xD;
      SPECIFIC OBJECTIVES AND HYPOTHESES&#xD;
&#xD;
      The proposed study (in conjunction with my current DCD-imaging-intervention study: H14-00397)&#xD;
      will allow us to compare brain structure and function in full-term children with DCD and in&#xD;
      preterm children with the disorder. While the investigators expect similar neural correlates&#xD;
      between the two groups, the investigators hypothesize that the preterm DCD may also show&#xD;
      unique brain differences, which may affect their response to rehabilitation. The&#xD;
      investigators will address two specific objectives as outlined below:&#xD;
&#xD;
      Objective 1: To characterize structural and functional brain differences in full-term and&#xD;
      preterm children with DCD.&#xD;
&#xD;
      Hypothesis: In our current study, the investigators hypothesized that, compared to&#xD;
      typically-developing children, children with full-term DCD will show smaller cerebellar&#xD;
      volume, differences in microstructural development in motor, sensory and cerebellar pathways,&#xD;
      and decreased strength of connectivity in resting, default mode, and motor networks. The&#xD;
      investigators expect that preterm children will show similar structural and functional brain&#xD;
      differences as full-term children with DCD, but that they may also show mild white matter&#xD;
      injury.&#xD;
&#xD;
      Approach: The investigators will use magnetic resonance (MR) imaging and advanced MR&#xD;
      techniques to characterize brain structure and function; the investigators will use&#xD;
      morphometry to measure cerebral and cerebellar volumes, diffusion tensor imaging (DTI) to&#xD;
      assess microstructural development, and functional connectivity MRI to measure connectivity&#xD;
      in different brain networks. The investigators will also explore fMRI during a mental&#xD;
      rotation task and spectroscopy of the basal ganglia.&#xD;
&#xD;
      Objective 2: To determine if current best-practice rehabilitation intervention induces&#xD;
      neuroplastic changes in brain structure/function and positive outcomes in preterm children&#xD;
      with DCD.&#xD;
&#xD;
      Hypotheses: Compared to their waitlist scan, the investigators expect that post-treatment&#xD;
      scans of preterm children will show: (1) strengthened functional connectivity in resting,&#xD;
      default mode, and motor networks; (2) increased integrity of the frontal-cerebellar pathway;&#xD;
      (3) increased gray matter volume in the dorsolateral prefrontal, motor and cerebellar&#xD;
      cortices; and (4) improved performance and satisfaction ratings of child-chosen functional&#xD;
      motor goals. The investigators also expect that there will be a positive association between&#xD;
      functional improvements and changes in brain structure/function.&#xD;
&#xD;
      Approach: The investigators will measure brain changes at three time points: once before a&#xD;
      waiting period as a baseline scan (conducted as part of the Miller-Grunau Trajectories study&#xD;
      at age 8-9 years: C05-0579), once immediately before beginning treatment (12 weeks after the&#xD;
      first scan), and once after 12 weeks of intervention. As part of treatment, children will&#xD;
      identify three functional motor goals as a target for intervention. The investigators will&#xD;
      use the Canadian Occupational Performance Measure (COPM; Law et al., 2005) to measure the&#xD;
      child's rating of their performance and satisfaction pre- and post-intervention. To&#xD;
      supplement the COPM, the investigators will videotape the child performing each of their&#xD;
      motor goals before and after intervention, and an independent occupational therapist will use&#xD;
      the Performance Quality Rating Scale (PQRS) to objectively measure performance and change in&#xD;
      performance (Miller et al., 2001). As a secondary measure, the investigators will evaluate&#xD;
      fine and gross motor skills using the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2:&#xD;
      Bruininks &amp; Bruininks, 2005).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 26, 2016</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Participants are either recruited from the Trajectories Study at their 8-year follow-up visit where the Neonatal Follow-Up Team has determined that the child has DCD and meets inclusion criteria for the study, or participants may contact the research coordinator after seeing a recruitment flyer for this study.&#xD;
Both groups will receive occupational therapy once weekly for 10 weeks using the published protocol for the CO-OP approach.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The occupational therapist assessing the filming of child performing their 3 goals at week 1 and 10 will be blinded to which week the the goals were performed.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Canadian Occupational Performance Measure (COPM)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Children will rate performance and satisfaction (10 point Likert scale) of their three motor goals. The OT calculates an average COPM performance score and satisfaction score. These typically range between 1 and 10, and 1 indicates poor performance and low satisfaction, respectively, while 10 indicates very good performance and high satisfaction. A change of 2 points indicates a clinically significant change.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Diffusion Tensor Imaging</measure>
    <time_frame>12 weeks</time_frame>
    <description>Fractional anisotrophy and diffusivity (mean, axial and radial)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bruininks Osteretsky Test of Motor Proficiency (BOT-2)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Standardized assessment of motor skills. The investigators will measures fine and gross motor skills using the short form of the BOT-2 which assesses 14 items divided between fine manual control, manual coordination, body coordination, and strength/agility. The results are both Standard Score and Percentile Rank. The higher percentile means better motor skills.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Performance Quality Rating Scale (PQRS)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Qualitative observations of movement quality. An independent occupational therapist blinded to the intervention will score the motor performance using the Performance Quality Rating Scale (PQRS) which is composed of Part A, a 10-point performance rating scale to rate actual performance, and Part B, an 11-point magnitude of change scale to rate differences in performance between pre- and post-intervention (down to -5 for worse performance, 0 for no change, and up to +5 for improved performance). A higher change score indicates more improvement. An increase of 3 points is considered clinically significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional connectivity</measure>
    <time_frame>12 weeks</time_frame>
    <description>Spatial independent components analysis of resting state networks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional magnetic resonance imaging</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patterns of brain activation during mental rotation task</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Morphometry (brain volume)</measure>
    <time_frame>12 weeks</time_frame>
    <description>White matter, cortical gray matter, deep gray matter, and total volumes for cerebrum and cerebellum</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Motor Skills Disorders</condition>
  <condition>Premature Birth</condition>
  <arm_group>
    <arm_group_label>Waitlist</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Waitlist Participants are first allocated to a waitlist condition. After the first MRI scan, participants &quot;wait&quot; for 12 weeks and have a second MRI scan.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Upon completion on the waitlist time of 12 weeks, participants then are allocated to the treatment group. Participants are assessed by an independent occupational therapist (before and after intervention) and participate in 10 treatment sessions with a treating occupational therapist. Following the post-treatment assessment, participants have a third MRI scan.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cognitive Orientation to Occupational Performance (CO-OP)</intervention_name>
    <description>Intervention: CO-OP is a cognitive approach to solving functional motor problems (Polatajko et al., 2001b). Therapists teach children a global problem solving strategy (Goal-Plan-Do-Check) as a framework for developing specific strategies for overcoming motor problems; these strategies are determined after a dynamic performance analysis by the therapist to determine where the &quot;breakdown&quot; is in performing the task. CO-OP intervention will be administered by occupational therapists who have been trained in the CO-OP approach. Children will be seen once weekly for one hour over 12 weeks at as per published protocol (Polatajko et al., 2001b). Parents or caregivers will be encouraged to attend treatment sessions so that therapists can instruct them how to facilitate strategy use between treatment sessions. Children will select three functional motor goals to be addressed over the course of treatment, rating their performance and satisfaction of these goals pre- and post-intervention.</description>
    <arm_group_label>Treatment arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Our targeted sample size is 15.&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  children who were born very preterm (≤ 32weeks gestational age)&#xD;
&#xD;
          -  8-12 years of age&#xD;
&#xD;
          -  diagnosed with DCD (either in the community or at the Neonatal Follow-Up Program at BC&#xD;
             Women's Hospital as part as of the Miller/Grunau Trajectories study)&#xD;
&#xD;
          -  live in the Greater Vancouver or surrounding areas&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  children with other diagnoses that may confound the results (e.g., intellectual&#xD;
             disability, visual impairment)&#xD;
&#xD;
          -  children who have metal anywhere in their body&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jill G Zwicker, PhD, OT(C)</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jill G Zwicker, PhD, OT(C)</last_name>
    <phone>604-875-2345</phone>
    <phone_ext>5948</phone_ext>
    <email>jill.zwicker@ubc.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nur Eisma</last_name>
    <phone>604-875-2427</phone>
    <email>neisma@bcchr.ubc.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of British Columbia</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6H 3V4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gisela Gosse, BScN</last_name>
      <phone>604-875-2345</phone>
      <phone_ext>5948</phone_ext>
      <email>ggosse@cw.bc.ca</email>
    </contact>
    <contact_backup>
      <last_name>Janet Rigney</last_name>
      <phone>604-875-2345</phone>
      <phone_ext>5948</phone_ext>
      <email>jrigney@cw.bc.ca</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Zwicker JG, Harris SR, Klassen AF. Quality of life domains affected in children with developmental coordination disorder: a systematic review. Child Care Health Dev. 2013 Jul;39(4):562-80. doi: 10.1111/j.1365-2214.2012.01379.x. Epub 2012 Apr 20.</citation>
    <PMID>22515477</PMID>
  </reference>
  <reference>
    <citation>Edwards J, Berube M, Erlandson K, Haug S, Johnstone H, Meagher M, Sarkodee-Adoo S, Zwicker JG. Developmental coordination disorder in school-aged children born very preterm and/or at very low birth weight: a systematic review. J Dev Behav Pediatr. 2011 Nov;32(9):678-87. doi: 10.1097/DBP.0b013e31822a396a.</citation>
    <PMID>21900828</PMID>
  </reference>
  <reference>
    <citation>Zwicker JG, Missiuna C, Harris SR, Boyd LA. Brain activation of children with developmental coordination disorder is different than peers. Pediatrics. 2010 Sep;126(3):e678-86. doi: 10.1542/peds.2010-0059. Epub 2010 Aug 16.</citation>
    <PMID>20713484</PMID>
  </reference>
  <reference>
    <citation>Zwicker JG, Missiuna C, Harris SR, Boyd LA. Developmental coordination disorder: a pilot diffusion tensor imaging study. Pediatr Neurol. 2012 Mar;46(3):162-7. doi: 10.1016/j.pediatrneurol.2011.12.007.</citation>
    <PMID>22353291</PMID>
  </reference>
  <reference>
    <citation>Miller LT, Polatajko HJ, Missiuna C, Mandich AD, Macnab JJ. A pilot trial of a cognitive treatment for children with developmental coordination disorder. Hum Mov Sci. 2001 Mar;20(1-2):183-210. doi: 10.1016/s0167-9457(01)00034-3.</citation>
    <PMID>11471396</PMID>
  </reference>
  <reference>
    <citation>Polatajko HJ, Mandich AD, Missiuna C, Miller LT, Macnab JJ, Malloy-Miller T, Kinsella EA. Cognitive orientation to daily occupational performance (CO-OP): part III--the protocol in brief. Phys Occup Ther Pediatr. 2001;20(2-3):107-23.</citation>
    <PMID>11345506</PMID>
  </reference>
  <reference>
    <citation>Wann J. Current approaches to intervention in children with developmental coordination disorder. Dev Med Child Neurol. 2007 Jun;49(6):405. doi: 10.1111/j.1469-8749.2007.00405.x. No abstract available.</citation>
    <PMID>17518922</PMID>
  </reference>
  <reference>
    <citation>Statistics Canada. Population by sex and age group. http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo10a-eng.htm. Published 2014. Accessed January 5, 2015.</citation>
  </reference>
  <reference>
    <citation>Cantell MH, Smyth MM, Ahonen TP. Two distinct pathways for developmental coordination disorder: persistence and resolution. Hum Mov Sci. 2003 Nov;22(4-5):413-31. doi: 10.1016/j.humov.2003.09.002.</citation>
    <PMID>14624826</PMID>
  </reference>
  <reference>
    <citation>Cousins M, Smyth MM. Developmental coordination impairments in adulthood. Hum Mov Sci. 2003 Nov;22(4-5):433-59. doi: 10.1016/j.humov.2003.09.003.</citation>
    <PMID>14624827</PMID>
  </reference>
  <reference>
    <citation>Kadesjo B, Gillberg C. Developmental coordination disorder in Swedish 7-year-old children. J Am Acad Child Adolesc Psychiatry. 1999 Jul;38(7):820-8. doi: 10.1097/00004583-199907000-00011.</citation>
    <PMID>10405499</PMID>
  </reference>
  <reference>
    <citation>Blank R, Smits-Engelsman B, Polatajko H, Wilson P; European Academy for Childhood Disability. European Academy for Childhood Disability (EACD): recommendations on the definition, diagnosis and intervention of developmental coordination disorder (long version). Dev Med Child Neurol. 2012 Jan;54(1):54-93. doi: 10.1111/j.1469-8749.2011.04171.x. No abstract available.</citation>
    <PMID>22171930</PMID>
  </reference>
  <reference>
    <citation>Querne L, Berquin P, Vernier-Hauvette MP, Fall S, Deltour L, Meyer ME, de Marco G. Dysfunction of the attentional brain network in children with Developmental Coordination Disorder: a fMRI study. Brain Res. 2008 Dec 9;1244:89-102. doi: 10.1016/j.brainres.2008.07.066. Epub 2008 Jul 29.</citation>
    <PMID>18718456</PMID>
  </reference>
  <reference>
    <citation>Kashiwagi M, Iwaki S, Narumi Y, Tamai H, Suzuki S. Parietal dysfunction in developmental coordination disorder: a functional MRI study. Neuroreport. 2009 Oct 7;20(15):1319-24. doi: 10.1097/WNR.0b013e32832f4d87.</citation>
    <PMID>19730138</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>November 7, 2019</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>July 20, 2020</last_update_submitted>
  <last_update_submitted_qc>July 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of British Columbia</investigator_affiliation>
    <investigator_full_name>Jill Zwicker</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>DCD</keyword>
  <keyword>Premature Birth</keyword>
  <keyword>Neuroimaging</keyword>
  <keyword>Rehabilitation</keyword>
  <keyword>Motor Skills</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Motor Skills Disorders</mesh_term>
  </condition_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/NCT04483401
org study id: H16-00358
nct id: NCT04483401
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will leverage a current longitudinal study of brain development in preterm
      children. In the Miller/Grunau Trajectories study, preterm children are returning for
      follow-up at 8-9 years. At this appointment, children undergo MRI and neurodevelopmental
      testing. Children who are identified with DCD at this appointment will be invited to
      participate in this intervention study. Participants will have a 2nd MRI 12 weeks after the
      first scan. They will then receive 12 weekly sessions with an occupational therapist,
      followed by a third MRI.

      Children with DCD who were born very preterm (<32 weeks gestational age) who are not part of
      the Miller/Grunau study are also eligible to participate.
RATIONALE Developmental coordination disorder (DCD) is one of the most common disorders in
      children (Wann, 2007), affecting 5-6% of the school-age population; this is > 400,000
      children in Canada, or 1-2 children in every classroom (American Psychiatric Association,
      2013; Statistics Canada, 2013). Compared with children born at term, preterm children (born
      2-4 months early) are 6-8 times more likely to develop DCD (Edwards…Zwicker, 2011). DCD
      significantly interferes with a child's ability to learn motor skills and to perform everyday
      activities, such as getting dressed, tying shoelaces, using a knife and fork, printing,
      playing sports, or riding a bicycle. While it was once believed that children would outgrow
      this condition, longitudinal research has shown that functional difficulties can persist into
      adolescence and adulthood (Cantell, Smyth, & Ahonen, 2003; Cousins & Smyth, 2003).
      Furthermore, secondary psychosocial difficulties often develop, including poor self-esteem,
      depression, anxiety, problems with peers, loneliness, and decreased participation in physical
      and social activities (Zwicker, Harris, & Klassen, 2013). Up to half of children with DCD
      will have co-occurring attention deficit hyperactivity disorder (ADHD) (Kadesjo & Gillberg,
      1998). As a chronic health condition, DCD often interferes with an individual's function and
      quality of life across their lifespan (Cousins & Smyth, 2003; Zwicker et al., 2013)

      The cause of DCD is not known, and it is under-recognized, under-diagnosed, and under-treated
      (Blank et al., 2012). In particular, the investigators do not understand the neural basis of
      DCD, making it difficult to understand why children with DCD struggle to learn motor skills
      and to determine how to best intervene to optimize function.

      To change the negative trajectory of children with DCD, the investigators need a better
      understanding of the neural basis of DCD, along with further rehabilitation efforts to
      improve outcomes. Recently, the investigators and others have conducted small neuroimaging
      studies to begin to understand brain differences in DCD (Querne et al., 2008; Kashiwagi et
      al., 2009, Zwicker et al., 2010, 2011, 2012b). These studies, while novel and significant in
      advancing the field of DCD, are limited by small sample sizes. To further define the neural
      correlates of DCD, the investigators need to perform larger studies and take advantage of new
      neuroimaging techniques. To date, no studies have examined neural correlates of DCD in the
      preterm population, a group that is at particularly high risk for the disorder. In addition,
      brain imaging studies may determine whether improvements in motor function with current "best
      practice" rehabilitation intervention are associated with changes in brain
      structure/function. A greater understanding of the neural basis of DCD may result in earlier
      diagnosis and early rehabilitation to mediate better brain development.

      Currently, the investigators have a study underway that assesses whether rehabilitation
      intervention and improved outcomes in children with DCD are associated with concurrent brain
      changes (H14-00397). This proposed research extends this study to determine whether preterm
      children with DCD show similar brain changes.

      SPECIFIC OBJECTIVES AND HYPOTHESES

      The proposed study (in conjunction with my current DCD-imaging-intervention study: H14-00397)
      will allow us to compare brain structure and function in full-term children with DCD and in
      preterm children with the disorder. While the investigators expect similar neural correlates
      between the two groups, the investigators hypothesize that the preterm DCD may also show
      unique brain differences, which may affect their response to rehabilitation. The
      investigators will address two specific objectives as outlined below:

      Objective 1: To characterize structural and functional brain differences in full-term and
      preterm children with DCD.

      Hypothesis: In our current study, the investigators hypothesized that, compared to
      typically-developing children, children with full-term DCD will show smaller cerebellar
      volume, differences in microstructural development in motor, sensory and cerebellar pathways,
      and decreased strength of connectivity in resting, default mode, and motor networks. The
      investigators expect that preterm children will show similar structural and functional brain
      differences as full-term children with DCD, but that they may also show mild white matter
      injury.

      Approach: The investigators will use magnetic resonance (MR) imaging and advanced MR
      techniques to characterize brain structure and function; the investigators will use
      morphometry to measure cerebral and cerebellar volumes, diffusion tensor imaging (DTI) to
      assess microstructural development, and functional connectivity MRI to measure connectivity
      in different brain networks. The investigators will also explore fMRI during a mental
      rotation task and spectroscopy of the basal ganglia.

      Objective 2: To determine if current best-practice rehabilitation intervention induces
      neuroplastic changes in brain structure/function and positive outcomes in preterm children
      with DCD.

      Hypotheses: Compared to their waitlist scan, the investigators expect that post-treatment
      scans of preterm children will show: (1) strengthened functional connectivity in resting,
      default mode, and motor networks; (2) increased integrity of the frontal-cerebellar pathway;
      (3) increased gray matter volume in the dorsolateral prefrontal, motor and cerebellar
      cortices; and (4) improved performance and satisfaction ratings of child-chosen functional
      motor goals. The investigators also expect that there will be a positive association between
      functional improvements and changes in brain structure/function.

      Approach: The investigators will measure brain changes at three time points: once before a
      waiting period as a baseline scan (conducted as part of the Miller-Grunau Trajectories study
      at age 8-9 years: C05-0579), once immediately before beginning treatment (12 weeks after the
      first scan), and once after 12 weeks of intervention. As part of treatment, children will
      identify three functional motor goals as a target for intervention. The investigators will
      use the Canadian Occupational Performance Measure (COPM; Law et al., 2005) to measure the
      child's rating of their performance and satisfaction pre- and post-intervention. To
      supplement the COPM, the investigators will videotape the child performing each of their
      motor goals before and after intervention, and an independent occupational therapist will use
      the Performance Quality Rating Scale (PQRS) to objectively measure performance and change in
      performance (Miller et al., 2001). As a secondary measure, the investigators will evaluate
      fine and gross motor skills using the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2:
      Bruininks & Bruininks, 2005).
allocation: Non-Randomized
intervention model: Crossover Assignment
intervention model description: Participants are either recruited from the Trajectories Study at their 8-year follow-up visit where the Neonatal Follow-Up Team has determined that the child has DCD and meets inclusion criteria for the study, or participants may contact the research coordinator after seeing a recruitment flyer for this study.
Both groups will receive occupational therapy once weekly for 10 weeks using the published protocol for the CO-OP approach.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The occupational therapist assessing the filming of child performing their 3 goals at week 1 and 10 will be blinded to which week the the goals were performed.
measure: Canadian Occupational Performance Measure (COPM)
time frame: 12 weeks
description: Children will rate performance and satisfaction (10 point Likert scale) of their three motor goals. The OT calculates an average COPM performance score and satisfaction score. These typically range between 1 and 10, and 1 indicates poor performance and low satisfaction, respectively, while 10 indicates very good performance and high satisfaction. A change of 2 points indicates a clinically significant change.
measure: Diffusion Tensor Imaging
time frame: 12 weeks
description: Fractional anisotrophy and diffusivity (mean, axial and radial)
measure: Bruininks Osteretsky Test of Motor Proficiency (BOT-2)
time frame: 12 weeks
description: Standardized assessment of motor skills. The investigators will measures fine and gross motor skills using the short form of the BOT-2 which assesses 14 items divided between fine manual control, manual coordination, body coordination, and strength/agility. The results are both Standard Score and Percentile Rank. The higher percentile means better motor skills.
measure: Performance Quality Rating Scale (PQRS)
time frame: 12 weeks
description: Qualitative observations of movement quality. An independent occupational therapist blinded to the intervention will score the motor performance using the Performance Quality Rating Scale (PQRS) which is composed of Part A, a 10-point performance rating scale to rate actual performance, and Part B, an 11-point magnitude of change scale to rate differences in performance between pre- and post-intervention (down to -5 for worse performance, 0 for no change, and up to +5 for improved performance). A higher change score indicates more improvement. An increase of 3 points is considered clinically significant.
measure: Functional connectivity
time frame: 12 weeks
description: Spatial independent components analysis of resting state networks
measure: Functional magnetic resonance imaging
time frame: 12 weeks
description: Patterns of brain activation during mental rotation task
measure: Morphometry (brain volume)
time frame: 12 weeks
description: White matter, cortical gray matter, deep gray matter, and total volumes for cerebrum and cerebellum
arm group label: Waitlist
arm group type: No Intervention
description: Waitlist Participants are first allocated to a waitlist condition. After the first MRI scan, participants "wait" for 12 weeks and have a second MRI scan.
arm group label: Treatment arm
arm group type: Experimental
description: Upon completion on the waitlist time of 12 weeks, participants then are allocated to the treatment group. Participants are assessed by an independent occupational therapist (before and after intervention) and participate in 10 treatment sessions with a treating occupational therapist. Following the post-treatment assessment, participants have a third MRI scan.
intervention type: Behavioral
intervention name: Cognitive Orientation to Occupational Performance (CO-OP)
description: Intervention: CO-OP is a cognitive approach to solving functional motor problems (Polatajko et al., 2001b). Therapists teach children a global problem solving strategy (Goal-Plan-Do-Check) as a framework for developing specific strategies for overcoming motor problems; these strategies are determined after a dynamic performance analysis by the therapist to determine where the "breakdown" is in performing the task. CO-OP intervention will be administered by occupational therapists who have been trained in the CO-OP approach. Children will be seen once weekly for one hour over 12 weeks at as per published protocol (Polatajko et al., 2001b). Parents or caregivers will be encouraged to attend treatment sessions so that therapists can instruct them how to facilitate strategy use between treatment sessions. Children will select three functional motor goals to be addressed over the course of treatment, rating their performance and satisfaction of these goals pre- and post-intervention.
arm group label: Treatment arm
criteria: 
gender: All
minimum age: 8 Years
maximum age: 12 Years
healthy volunteers: No
last name: Jill G Zwicker, PhD, OT(C)
role: Principal Investigator
affiliation: University of British Columbia
last name: Jill G Zwicker, PhD, OT(C)
phone: 604-875-2345
phone ext: 5948
email: jill.zwicker@ubc.ca
last name: Nur Eisma
phone: 604-875-2427
email: neisma@bcchr.ubc.ca
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
citation: Zwicker JG, Harris SR, Klassen AF. Quality of life domains affected in children with developmental coordination disorder: a systematic review. Child Care Health Dev. 2013 Jul;39(4):562-80. doi: 10.1111/j.1365-2214.2012.01379.x. Epub 2012 Apr 20.
PMID: 22515477
citation: Edwards J, Berube M, Erlandson K, Haug S, Johnstone H, Meagher M, Sarkodee-Adoo S, Zwicker JG. Developmental coordination disorder in school-aged children born very preterm and/or at very low birth weight: a systematic review. J Dev Behav Pediatr. 2011 Nov;32(9):678-87. doi: 10.1097/DBP.0b013e31822a396a.
PMID: 21900828
citation: Zwicker JG, Missiuna C, Harris SR, Boyd LA. Brain activation of children with developmental coordination disorder is different than peers. Pediatrics. 2010 Sep;126(3):e678-86. doi: 10.1542/peds.2010-0059. Epub 2010 Aug 16.
PMID: 20713484
citation: Zwicker JG, Missiuna C, Harris SR, Boyd LA. Developmental coordination disorder: a pilot diffusion tensor imaging study. Pediatr Neurol. 2012 Mar;46(3):162-7. doi: 10.1016/j.pediatrneurol.2011.12.007.
PMID: 22353291
citation: Miller LT, Polatajko HJ, Missiuna C, Mandich AD, Macnab JJ. A pilot trial of a cognitive treatment for children with developmental coordination disorder. Hum Mov Sci. 2001 Mar;20(1-2):183-210. doi: 10.1016/s0167-9457(01)00034-3.
PMID: 11471396
citation: Polatajko HJ, Mandich AD, Missiuna C, Miller LT, Macnab JJ, Malloy-Miller T, Kinsella EA. Cognitive orientation to daily occupational performance (CO-OP): part III--the protocol in brief. Phys Occup Ther Pediatr. 2001;20(2-3):107-23.
PMID: 11345506
citation: Wann J. Current approaches to intervention in children with developmental coordination disorder. Dev Med Child Neurol. 2007 Jun;49(6):405. doi: 10.1111/j.1469-8749.2007.00405.x. No abstract available.
PMID: 17518922
citation: Statistics Canada. Population by sex and age group. http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo10a-eng.htm. Published 2014. Accessed January 5, 2015.
citation: Cantell MH, Smyth MM, Ahonen TP. Two distinct pathways for developmental coordination disorder: persistence and resolution. Hum Mov Sci. 2003 Nov;22(4-5):413-31. doi: 10.1016/j.humov.2003.09.002.
PMID: 14624826
citation: Cousins M, Smyth MM. Developmental coordination impairments in adulthood. Hum Mov Sci. 2003 Nov;22(4-5):433-59. doi: 10.1016/j.humov.2003.09.003.
PMID: 14624827
citation: Kadesjo B, Gillberg C. Developmental coordination disorder in Swedish 7-year-old children. J Am Acad Child Adolesc Psychiatry. 1999 Jul;38(7):820-8. doi: 10.1097/00004583-199907000-00011.
PMID: 10405499
citation: Blank R, Smits-Engelsman B, Polatajko H, Wilson P; European Academy for Childhood Disability. European Academy for Childhood Disability (EACD): recommendations on the definition, diagnosis and intervention of developmental coordination disorder (long version). Dev Med Child Neurol. 2012 Jan;54(1):54-93. doi: 10.1111/j.1469-8749.2011.04171.x. No abstract available.
PMID: 22171930
citation: Querne L, Berquin P, Vernier-Hauvette MP, Fall S, Deltour L, Meyer ME, de Marco G. Dysfunction of the attentional brain network in children with Developmental Coordination Disorder: a fMRI study. Brain Res. 2008 Dec 9;1244:89-102. doi: 10.1016/j.brainres.2008.07.066. Epub 2008 Jul 29.
PMID: 18718456
citation: Kashiwagi M, Iwaki S, Narumi Y, Tamai H, Suzuki S. Parietal dysfunction in developmental coordination disorder: a functional MRI study. Neuroreport. 2009 Oct 7;20(15):1319-24. doi: 10.1097/WNR.0b013e32832f4d87.
PMID: 19730138
responsible party type: Principal Investigator
investigator affiliation: University of British Columbia
investigator full name: Jill Zwicker
investigator title: Principal Investigator
mesh term: Premature Birth
mesh term: Motor Skills Disorders