xml: <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/NCT06018519</url>
    </required_header>
    <id_info>
      <org_study_id>69HCL21_0655</org_study_id>
      <secondary_id>2022-A02063-40</secondary_id>
      <nct_id>NCT06018519</nct_id>
    </id_info>
    <brief_title>Relevant Outcome Measures for Creatine Transporter Deficiency Patient</brief_title>
    <acronym>CREAT_criteria</acronym>
    <official_title>A Prospective Study in Creatine Transporter Deficiency (SLC6A8) Patients to Determine the Most Relevant Outcome Measures</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Hospices Civils de Lyon</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Hospices Civils de Lyon</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>
        Creatine transport deficiency (CTD) is a rare genetic disorder related to pathogenic variants&#xD;
        in the SLC6A8 gene, located on chromosome Xq28. Clinical diagnosis of CTD is based on&#xD;
        clinical presentation, an increased urinary creatine/creatinine ratio and a severe decreased&#xD;
        creatine peak on 1H-MRS magnetic resonance spectroscopy.&#xD;
  &#xD;
        A retrospective study with questionnaires identified that most CTD patients had moderate to&#xD;
        severe intellectual disability. Less than one third of patients were able to speak in&#xD;
        sentences. Seizures were present in 59% of the patients. 41% had autistic features. Motor&#xD;
        dysfunction was mentioned in 58%, and gastrointestinal symptoms were reported in 35% of the&#xD;
        patients.&#xD;
  &#xD;
        Several new therapeutic avenues are currently emerging in this disease for which no treatment&#xD;
        has been available until now : cyclocreatine (interesting but unfortunately with very little&#xD;
        clinical applicability due to its toxicity; dodecyl creatine ester incorporated into lipid&#xD;
        nanocapsules with intranasal administration; pharmaco-chaperoning (for the folding-deficient&#xD;
        creatine transporter variants, Ultragenyx pharmaceuticals new prodrug designed to deliver&#xD;
        creatine to the brain (UX068). These new pharmacological treatment options may offer future&#xD;
        opportunities to improve cognition in CTD patients.&#xD;
  &#xD;
        A key issue is to determine outcome measures that are accessible to these patients, despite&#xD;
        the importance of their cognitive deficit. In a preliminary study (on 31 CTD patients),&#xD;
        investigators showed for example, that 75% of patients were unable to perform a Wechsler&#xD;
        scale, which is one of the most used neuropsychological test to determine patient IQ&#xD;
        (intelligence quotient). Most of the existing cognitive tests were developed to distinguish&#xD;
        typically developing persons and ID (intellectual disability) patients, leading to a floor&#xD;
        effect in the latter who systematically fail these tests. Therefore, these tests are not&#xD;
        adapted to capture the potential effect of a drug in ID patient group. The identification of&#xD;
        reliable and sensitive outcome measures for use in clinical trials in ID patients was&#xD;
        recognized as a priority in a meeting convened by the NIH. N-of-1 trials (also called&#xD;
        Single-Case Experimental Designs or SCEDs) appear of great interest for rare diseases,&#xD;
        statistical power coming from the number of repeated measures, which leads to choose outcome&#xD;
        measures that can be repeated multiple times.&#xD;
  &#xD;
        This innovative study will allow to efficiently preparing future therapeutic trials, by&#xD;
        specifying the phenotype of the patients, and by determining the most adapted outcome&#xD;
        measures taking into account their cognitive deficiency and the type of experimental design&#xD;
        to be used in the context of rare diseases.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 13, 2023</start_date>
    <completion_date type="Anticipated">September 2024</completion_date>
    <primary_completion_date type="Anticipated">September 2024</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>Parallel Assignment</intervention_model>
      <primary_purpose>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Clinical endpoints : number of epileptic seizures</measure>
      <time_frame>Up to 90 Days</time_frame>
      <description>Number of epileptic seizures</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical endpoints : antiepileptic treatment</measure>
      <time_frame>For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).</time_frame>
      <description>Change in antiepileptic treatment (increase or decrease)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical endpoints : Visual analogical scale</measure>
      <time_frame>Up to 90 Days</time_frame>
      <description>Visual analogical scale on a target symptom defined with the parents,</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical endpoints : actimetry</measure>
      <time_frame>Up to 90 Days</time_frame>
      <description>Actimetry data over 48 hours</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical endpoints : podometry</measure>
      <time_frame>Up to 90 Days</time_frame>
      <description>Podometry data over 24 hours</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical endpoints : walk test</measure>
      <time_frame>Up to 90 Days</time_frame>
      <description>6 minutes' walk test</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical endpoints : Clinical examination</measure>
      <time_frame>For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).</time_frame>
      <description>Clinical examination</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical endpoints :Feasibility of performing an MRI</measure>
      <time_frame>For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).</time_frame>
      <description>Feasibility of performing an MRI without any anesthesia on a mock scanner</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Parental questionnaires : Vineland Adaptive Behavior scale II</measure>
      <time_frame>For all 24 CTD patients: V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).</time_frame>
      <description>Adaptive assessment with Vineland Adaptive Behavior scale II</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Parental questionnaires : Mac Arthur questionnaire</measure>
      <time_frame>For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).</time_frame>
      <description>Mac Arthur questionnaire regarding language</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Parental questionnaires : PDD-MRS</measure>
      <time_frame>For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).</time_frame>
      <description>Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Parental questionnaires : Dunn sensory profile</measure>
      <time_frame>For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).</time_frame>
      <description>Dunn sensory profile</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Parental questionnaires : Aberrant Behavior Checklist</measure>
      <time_frame>For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).</time_frame>
      <description>Aberrant Behavior Checklist</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Parental questionnaires : Nisonger Child Behavior Rating form</measure>
      <time_frame>For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).</time_frame>
      <description>Nisonger Child Behavior Rating form</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Parental questionnaires : Social Responsiveness Scale 2</measure>
      <time_frame>For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).</time_frame>
      <description>Social Responsiveness Scale 2</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Parental questionnaires : impact on primary caregiver</measure>
      <time_frame>For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).</time_frame>
      <description>Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Quality of life scale</measure>
      <time_frame>For all 24 CTD patients: At V1 (Day1/Day2) For 9 out of 24 CTD patients: Repeated at V3 (Day30) and V7 (Day90).</time_frame>
      <description>Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cognitive assessments : Leiter 3 scale</measure>
      <time_frame>For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)</time_frame>
      <description>Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cognitive assessments : CPM-BF</measure>
      <time_frame>For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)</time_frame>
      <description>CPM-BF : Raven's coloured Progressive Matrices</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cognitive assessments : reasoning task</measure>
      <time_frame>For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)</time_frame>
      <description>Simple reasoning task on tablet (match-to-sample task)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cognitive assessments : Implicit rules learning</measure>
      <time_frame>For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)</time_frame>
      <description>Implicit rules learning (modified Brixton),</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cognitive assessments : WPPSI-IV</measure>
      <time_frame>For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)</time_frame>
      <description>4 sub-tests from the WPPSI-IV (&quot;zoo location&quot; to assess spatial memory, &quot;block design&quot; to assess visuo-constructive abilities, &quot;bug search&quot; , &quot;cancellation&quot;),</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cognitive assessments : Attention assessment</measure>
      <time_frame>For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)</time_frame>
      <description>Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cognitive assessments : Elementary visuo-spatial perception</measure>
      <time_frame>For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)</time_frame>
      <description>Elementary visuo-spatial perception (on tablets)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Language assessments : EXALANG 3-6</measure>
      <time_frame>For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)</time_frame>
      <description>EXALANG 3-6 - Computerized battery for the evaluation of oral and written language : 10 sub-tests testing for expressive and receptive language assessments</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Language assessments : vocabulary</measure>
      <time_frame>For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)</time_frame>
      <description>PPVT-5 : Peabody Picture Vocabulary Test Fifth Edition = receptive vocabulary, EVT-3 : Expressive Vocabulary Test third edition,</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Language assessments : Automatic language analysis</measure>
      <time_frame>For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)</time_frame>
      <description>Automatic language analysis (during a 10 minutes interaction, play).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Motor assessments : Kinematic task</measure>
      <time_frame>CTD patients : performed at V1 (Day1/Day2). Controls: Motor assessment at V1 (Day 1)</time_frame>
      <description>Kinematic task (specifically designed)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Motor assessments : Purdue-Pegboard test</measure>
      <time_frame>CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)</time_frame>
      <description>Purdue-Pegboard test</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Motor assessments : Renzi test</measure>
      <time_frame>CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)</time_frame>
      <description>Renzi test</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Social assessments : Eye-tracking</measure>
      <time_frame>CTD patients : performed at V1 (Day1/Day2), V3 (Day30) and V7 (Day90). Controls : Social assessment at V1(Day1)</time_frame>
      <description>Eye-tracking analysis of social visual scenes and social preference index (movies)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Social assessments : Theory of mind assessment</measure>
      <time_frame>CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)</time_frame>
      <description>Theory of mind assessment</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Social assessments : ADOS scale (Autism Diagnostic Observation Scale)</measure>
      <time_frame>CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)</time_frame>
      <description>ADOS scale (Autism Spectrum Disorder)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Social assessments : Sensitivity to inequality</measure>
      <time_frame>CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)</time_frame>
      <description>Sensitivity to inequality</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Social assessments : Pro-social behaviors (help of the psychologist)</measure>
      <time_frame>CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)</time_frame>
      <description>Pro-social behaviors (help of the psychologist)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Neuroimaging (MRI)</measure>
      <time_frame>V1 (Day1/Day2)</time_frame>
      <description>The MRI will be performed to describe structural and functional neuroanatomical profile of CTD patient in comparison to chronological age-matched controls and variability in creatine peak assessment using MR spectroscopy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiac assessments : Electrocardiogram</measure>
      <time_frame>CTD patients: V1 (Day1/Day2)</time_frame>
      <description>Electrocardiogram (ECG) will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiac assessments : Ultrasound</measure>
      <time_frame>CTD patients: V1 (Day1/Day2)</time_frame>
      <description>Cardiac Ultrasound will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biological collection : Blood sample</measure>
      <time_frame>CTD patients: V1 (Day1/Day2)</time_frame>
      <description>Blood sample (plasma and peripheral blood mononuclear cells)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biological collection : Urine sample</measure>
      <time_frame>CTD patients: V1 (Day1/Day2)</time_frame>
      <description>Urine sample will be collected to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biological collection : Superficial skin biopsy</measure>
      <time_frame>CTD patients: V1 (Day1/Day2)</time_frame>
      <description>Superficial skin biopsy will be performed to get cultivated fibroblasts to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease.</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">152</enrollment>
    <condition>Creatine Transporter Defect</condition>
    <arm_group>
      <arm_group_label>CTD patients</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Case group 24 male CTD patients having a confirmed mutation in the SLC6A8 gene, aged &gt; 5 to &lt; 35 years.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sex and chronological age matched controls</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Control group 24 male, sex and chronological age matched controls, aged &gt; 5 to &lt; 35 years</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sex and mental age matched controls</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Control group 24 male, sex and mental age matched controls, aged &gt; 3 to &lt; 8 years</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Typically developed children</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Control group 80 typically developed children aged &gt; 3 to &lt; 8 years, which corresponds to the mental age of CTD patients.&#xD;
  40 children aged &gt; 3 to &lt; 5 years, and 40 children aged &gt; 6 to &lt; 8 years will perform the newly developed outcome measures.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Clinical endpoints</intervention_name>
      <description>Number of epileptic seizures&#xD;
  Change in antiepileptic treatment (increase or decrease)&#xD;
  Visual analogical scale on a target symptom defined with the parents,&#xD;
  CGI,&#xD;
  Actimetry data over 24 hours,&#xD;
  Podometry data over 24 hours,&#xD;
  6 minutes' walk test,&#xD;
  Clinical examination&#xD;
  Feasibility of performing an MRI without any anesthesia on a mock scanner</description>
      <arm_group_label>CTD patients</arm_group_label>
      <arm_group_label>Sex and chronological age matched controls</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Parental questionnaires</intervention_name>
      <description>10- Adaptive assessment with Vineland Adaptive Behavior scale II,&#xD;
  11- Mac Arthur questionnaire regarding language,&#xD;
  12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS),&#xD;
  13- Dunn sensory profile,&#xD;
  14- Aberrant Behavior Checklist,&#xD;
  15- Nisonger Child Behavior Rating form,&#xD;
  16- Social Responsiveness Scale 2,&#xD;
  17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)</description>
      <arm_group_label>CTD patients</arm_group_label>
      <arm_group_label>Sex and mental age matched controls</arm_group_label>
      <arm_group_label>Typically developed children</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Quality of life scale</intervention_name>
      <description>18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)</description>
      <arm_group_label>CTD patients</arm_group_label>
      <arm_group_label>Sex and chronological age matched controls</arm_group_label>
      <arm_group_label>Sex and mental age matched controls</arm_group_label>
      <arm_group_label>Typically developed children</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Cognitive assessments</intervention_name>
      <description>19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible&#xD;
  20- CPM-BF&#xD;
  21- Simple reasoning task on tablet (match-to-sample task)&#xD;
  22- Implicit rules learning (modified Brixton),&#xD;
  23- 4 sub-tests from the WPPSI-IV (&quot;zoo location&quot; to assess spatial memory, &quot;block design&quot; to assess visuo-constructive abilities, &quot;bug search&quot; , &quot;cancellation&quot;),&#xD;
  24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),&#xD;
  25- Elementary visuo-spatial perception (on tablets)</description>
      <arm_group_label>CTD patients</arm_group_label>
      <arm_group_label>Sex and chronological age matched controls</arm_group_label>
      <arm_group_label>Sex and mental age matched controls</arm_group_label>
      <arm_group_label>Typically developed children</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Language assessments</intervention_name>
      <description>26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments),&#xD;
  27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary),&#xD;
  28- Automatic language analysis (during a 10 minutes interaction, play).</description>
      <arm_group_label>CTD patients</arm_group_label>
      <arm_group_label>Sex and chronological age matched controls</arm_group_label>
      <arm_group_label>Sex and mental age matched controls</arm_group_label>
      <arm_group_label>Typically developed children</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Motor assessments</intervention_name>
      <description>29- Kinematic task (specifically designed),&#xD;
  30- Purdue-Pegboard test,&#xD;
  31- Renzi test</description>
      <arm_group_label>CTD patients</arm_group_label>
      <arm_group_label>Sex and chronological age matched controls</arm_group_label>
      <arm_group_label>Sex and mental age matched controls</arm_group_label>
      <arm_group_label>Typically developed children</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Social assessments</intervention_name>
      <description>32- Eye-tracking analysis of social visual scenes and social preference index (movies),&#xD;
  33- theory of mind assessment,&#xD;
  34- ADOS scale (Autism Spectrum Disorder),&#xD;
  35- sensitivity to inequality,&#xD;
  36- pro-social behaviors (help of the psychologist)</description>
      <arm_group_label>CTD patients</arm_group_label>
      <arm_group_label>Sex and chronological age matched controls</arm_group_label>
      <arm_group_label>Sex and mental age matched controls</arm_group_label>
      <arm_group_label>Typically developed children</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>3T MRI</intervention_name>
      <description>37- Structural, metabolic and functional data</description>
      <arm_group_label>CTD patients</arm_group_label>
      <arm_group_label>Sex and chronological age matched controls</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Cardiac assessments</intervention_name>
      <description>38- ECG&#xD;
  39- Ultrasound</description>
      <arm_group_label>CTD patients</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Biological collection</intervention_name>
      <description>40- Blood sample&#xD;
  41- Urinary sample&#xD;
  42- Superficial skin biopsy</description>
      <arm_group_label>CTD patients</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          CTD patients (n=24)&#xD;
  &#xD;
            -  Male CTD patients&#xD;
  &#xD;
            -  Having a confirmed mutation in the SLC6A8 gene,&#xD;
  &#xD;
            -  Aged &gt; 5 to &lt; 35 years&#xD;
  &#xD;
            -  Whose maternal language is French,&#xD;
  &#xD;
            -  Having signed the informed consent and/or for whom parents/legal guardian have signed&#xD;
               the informed consent,&#xD;
  &#xD;
            -  Affiliated to national Health Insurance system or parents/legal guardian affiliated to&#xD;
               national health insurance system.&#xD;
  &#xD;
          Sex- and chronological age-matched controls (n=24)&#xD;
  &#xD;
            -  Male&#xD;
  &#xD;
            -  Aged &gt; 5 to &lt; 35 years&#xD;
  &#xD;
            -  Whose maternal language is French,&#xD;
  &#xD;
            -  Having signed the informed consent and/or for whom parents/legal guardian have signed&#xD;
               the informed consent,&#xD;
  &#xD;
            -  Affiliated to national health insurance system or parents/legal guardian affiliated to&#xD;
               national health insurance system.&#xD;
  &#xD;
          Sex- and mental age-matched controls (n=24)&#xD;
  &#xD;
            -  Male&#xD;
  &#xD;
            -  Aged &gt; 3 to &lt; 8 years&#xD;
  &#xD;
            -  Whose maternal language is French,&#xD;
  &#xD;
            -  For whom parents/legal guardian have signed the informed consent,&#xD;
  &#xD;
            -  Affiliated to national health insurance system or parents/legal guardian affiliated to&#xD;
               national health insurance system.&#xD;
  &#xD;
          Typically developed children (n=80)&#xD;
  &#xD;
            -  Male and female&#xD;
  &#xD;
            -  Aged &gt; 3 to &lt; 8 years&#xD;
  &#xD;
            -  Whose maternal language is French,&#xD;
  &#xD;
            -  For whom parents/legal guardian have signed the informed consent,&#xD;
  &#xD;
            -  Affiliated to national health insurance system or parents/legal guardian affiliated to&#xD;
               national health insurance system.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          CTD patients (n=24):&#xD;
  &#xD;
            -  Having a contraindication to the MRI examination (people using a pacemaker or an&#xD;
               insulin pump, people wearing a metal prosthesis or an intracerebral clip, and&#xD;
               claustrophobic subjects),&#xD;
  &#xD;
            -  Refusal of the subject and/or the subject's parents to be informed of possible&#xD;
               abnormalities detected by MRI,&#xD;
  &#xD;
            -  Refusal of the subject and/or the subject's parents/legal guardian to be informed of&#xD;
               possible abnormalities detected during the cardiac assessment.&#xD;
  &#xD;
          Sex- and chronological age-matched controls (n=24)&#xD;
  &#xD;
            -  History of neurological or psychiatric disorder,&#xD;
  &#xD;
            -  Repetition of a grade,&#xD;
  &#xD;
            -  Learning disability requiring rehabilitation (speech therapy, psychomotor or&#xD;
               oculomotor therapy),&#xD;
  &#xD;
            -  For participants agreeing on performing the MRI examination, having a contraindication&#xD;
               to the MRI examination (use of a pacemaker or an insulin pump, people wearing a metal&#xD;
               prosthesis or an intracerebral clip, and claustrophobic subjects) and refusal of the&#xD;
               subject and/or the subject's parents/legal guardian to be informed of possible&#xD;
               abnormalities detected by MRI.&#xD;
  &#xD;
          Sex- and mental age-matched controls (n=24)&#xD;
  &#xD;
            -  History of neurological or psychiatric disorder,&#xD;
  &#xD;
            -  Repetition of a grade,&#xD;
  &#xD;
            -  Learning disability requiring rehabilitation (speech therapy, psychomotor or&#xD;
               oculomotor therapy).&#xD;
  &#xD;
          Typically developed children (n=80)&#xD;
  &#xD;
            -  History of neurological or psychiatric disorder,&#xD;
  &#xD;
            -  Repetition of a grade,&#xD;
  &#xD;
            -  Learning disability requiring rehabilitation (speech therapy, psychomotor or&#xD;
               oculomotor therapy).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>3 Years</minimum_age>
      <maximum_age>35 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Aurore CURIE, MD,PhD</last_name>
      <phone>06 70 62 69 76</phone>
      <phone_ext>+33</phone_ext>
      <email>aurore.curie@chu-lyon.fr</email>
    </overall_contact>
    <location>
      <facility>
        <name>Woman, mother and child hospital, Hospices Civils de Lyon</name>
        <address>
          <city>Bron</city>
          <zip>69500</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Aurore CURIE, MD,PhD</last_name>
        <phone>06 70 62 69 76</phone>
        <phone_ext>+33</phone_ext>
        <email>aurore.curie@chu-lyon.fr</email>
      </contact>
      <investigator>
        <last_name>Aurore CURIE, MD,PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>November 3, 2022</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Creatine Transporter Deficiency (SLC6A8)</keyword>
    <keyword>Outcome measures</keyword>
    <keyword>Therapeutics</keyword>
    <keyword>Feasibility</keyword>
    <keyword>Relevance</keyword>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06018519
  org study id: 69HCL21_0655
  secondary id: 2022-A02063-40
  nct id: NCT06018519
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Creatine transport deficiency (CTD) is a rare genetic disorder related to pathogenic variants
        in the SLC6A8 gene, located on chromosome Xq28. Clinical diagnosis of CTD is based on
        clinical presentation, an increased urinary creatine/creatinine ratio and a severe decreased
        creatine peak on 1H-MRS magnetic resonance spectroscopy.
  
        A retrospective study with questionnaires identified that most CTD patients had moderate to
        severe intellectual disability. Less than one third of patients were able to speak in
        sentences. Seizures were present in 59% of the patients. 41% had autistic features. Motor
        dysfunction was mentioned in 58%, and gastrointestinal symptoms were reported in 35% of the
        patients.
  
        Several new therapeutic avenues are currently emerging in this disease for which no treatment
        has been available until now : cyclocreatine (interesting but unfortunately with very little
        clinical applicability due to its toxicity; dodecyl creatine ester incorporated into lipid
        nanocapsules with intranasal administration; pharmaco-chaperoning (for the folding-deficient
        creatine transporter variants, Ultragenyx pharmaceuticals new prodrug designed to deliver
        creatine to the brain (UX068). These new pharmacological treatment options may offer future
        opportunities to improve cognition in CTD patients.
  
        A key issue is to determine outcome measures that are accessible to these patients, despite
        the importance of their cognitive deficit. In a preliminary study (on 31 CTD patients),
        investigators showed for example, that 75% of patients were unable to perform a Wechsler
        scale, which is one of the most used neuropsychological test to determine patient IQ
        (intelligence quotient). Most of the existing cognitive tests were developed to distinguish
        typically developing persons and ID (intellectual disability) patients, leading to a floor
        effect in the latter who systematically fail these tests. Therefore, these tests are not
        adapted to capture the potential effect of a drug in ID patient group. The identification of
        reliable and sensitive outcome measures for use in clinical trials in ID patients was
        recognized as a priority in a meeting convened by the NIH. N-of-1 trials (also called
        Single-Case Experimental Designs or SCEDs) appear of great interest for rare diseases,
        statistical power coming from the number of repeated measures, which leads to choose outcome
        measures that can be repeated multiple times.
  
        This innovative study will allow to efficiently preparing future therapeutic trials, by
        specifying the phenotype of the patients, and by determining the most adapted outcome
        measures taking into account their cognitive deficiency and the type of experimental design
        to be used in the context of rare diseases.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Other
  masking: None (Open Label)
  measure: Clinical endpoints : number of epileptic seizures
  time frame: Up to 90 Days
  description: Number of epileptic seizures
  measure: Clinical endpoints : antiepileptic treatment
  time frame: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
  description: Change in antiepileptic treatment (increase or decrease)
  measure: Clinical endpoints : Visual analogical scale
  time frame: Up to 90 Days
  description: Visual analogical scale on a target symptom defined with the parents,
  measure: Clinical endpoints : actimetry
  time frame: Up to 90 Days
  description: Actimetry data over 48 hours
  measure: Clinical endpoints : podometry
  time frame: Up to 90 Days
  description: Podometry data over 24 hours
  measure: Clinical endpoints : walk test
  time frame: Up to 90 Days
  description: 6 minutes' walk test
  measure: Clinical endpoints : Clinical examination
  time frame: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
  description: Clinical examination
  measure: Clinical endpoints :Feasibility of performing an MRI
  time frame: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
  description: Feasibility of performing an MRI without any anesthesia on a mock scanner
  measure: Parental questionnaires : Vineland Adaptive Behavior scale II
  time frame: For all 24 CTD patients: V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
  description: Adaptive assessment with Vineland Adaptive Behavior scale II
  measure: Parental questionnaires : Mac Arthur questionnaire
  time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).
  description: Mac Arthur questionnaire regarding language
  measure: Parental questionnaires : PDD-MRS
  time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
  description: Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS)
  measure: Parental questionnaires : Dunn sensory profile
  time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).
  description: Dunn sensory profile
  measure: Parental questionnaires : Aberrant Behavior Checklist
  time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
  description: Aberrant Behavior Checklist
  measure: Parental questionnaires : Nisonger Child Behavior Rating form
  time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
  description: Nisonger Child Behavior Rating form
  measure: Parental questionnaires : Social Responsiveness Scale 2
  time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
  description: Social Responsiveness Scale 2
  measure: Parental questionnaires : impact on primary caregiver
  time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).
  description: Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)
  measure: Quality of life scale
  time frame: For all 24 CTD patients: At V1 (Day1/Day2) For 9 out of 24 CTD patients: Repeated at V3 (Day30) and V7 (Day90).
  description: Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
  measure: Cognitive assessments : Leiter 3 scale
  time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
  description: Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
  measure: Cognitive assessments : CPM-BF
  time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
  description: CPM-BF : Raven's coloured Progressive Matrices
  measure: Cognitive assessments : reasoning task
  time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
  description: Simple reasoning task on tablet (match-to-sample task)
  measure: Cognitive assessments : Implicit rules learning
  time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
  description: Implicit rules learning (modified Brixton),
  measure: Cognitive assessments : WPPSI-IV
  time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
  description: 4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
  measure: Cognitive assessments : Attention assessment
  time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
  description: Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
  measure: Cognitive assessments : Elementary visuo-spatial perception
  time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
  description: Elementary visuo-spatial perception (on tablets)
  measure: Language assessments : EXALANG 3-6
  time frame: For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)
  description: EXALANG 3-6 - Computerized battery for the evaluation of oral and written language : 10 sub-tests testing for expressive and receptive language assessments
  measure: Language assessments : vocabulary
  time frame: For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)
  description: PPVT-5 : Peabody Picture Vocabulary Test Fifth Edition = receptive vocabulary, EVT-3 : Expressive Vocabulary Test third edition,
  measure: Language assessments : Automatic language analysis
  time frame: For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)
  description: Automatic language analysis (during a 10 minutes interaction, play).
  measure: Motor assessments : Kinematic task
  time frame: CTD patients : performed at V1 (Day1/Day2). Controls: Motor assessment at V1 (Day 1)
  description: Kinematic task (specifically designed)
  measure: Motor assessments : Purdue-Pegboard test
  time frame: CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)
  description: Purdue-Pegboard test
  measure: Motor assessments : Renzi test
  time frame: CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)
  description: Renzi test
  measure: Social assessments : Eye-tracking
  time frame: CTD patients : performed at V1 (Day1/Day2), V3 (Day30) and V7 (Day90). Controls : Social assessment at V1(Day1)
  description: Eye-tracking analysis of social visual scenes and social preference index (movies)
  measure: Social assessments : Theory of mind assessment
  time frame: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
  description: Theory of mind assessment
  measure: Social assessments : ADOS scale (Autism Diagnostic Observation Scale)
  time frame: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
  description: ADOS scale (Autism Spectrum Disorder)
  measure: Social assessments : Sensitivity to inequality
  time frame: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
  description: Sensitivity to inequality
  measure: Social assessments : Pro-social behaviors (help of the psychologist)
  time frame: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
  description: Pro-social behaviors (help of the psychologist)
  measure: Neuroimaging (MRI)
  time frame: V1 (Day1/Day2)
  description: The MRI will be performed to describe structural and functional neuroanatomical profile of CTD patient in comparison to chronological age-matched controls and variability in creatine peak assessment using MR spectroscopy
  measure: Cardiac assessments : Electrocardiogram
  time frame: CTD patients: V1 (Day1/Day2)
  description: Electrocardiogram (ECG) will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality)
  measure: Cardiac assessments : Ultrasound
  time frame: CTD patients: V1 (Day1/Day2)
  description: Cardiac Ultrasound will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality)
  measure: Biological collection : Blood sample
  time frame: CTD patients: V1 (Day1/Day2)
  description: Blood sample (plasma and peripheral blood mononuclear cells)
  measure: Biological collection : Urine sample
  time frame: CTD patients: V1 (Day1/Day2)
  description: Urine sample will be collected to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease.
  measure: Biological collection : Superficial skin biopsy
  time frame: CTD patients: V1 (Day1/Day2)
  description: Superficial skin biopsy will be performed to get cultivated fibroblasts to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease.
  arm group label: CTD patients
  arm group type: Other
  description: Case group 24 male CTD patients having a confirmed mutation in the SLC6A8 gene, aged > 5 to < 35 years.
  arm group label: Sex and chronological age matched controls
  arm group type: Other
  description: Control group 24 male, sex and chronological age matched controls, aged > 5 to < 35 years
  arm group label: Sex and mental age matched controls
  arm group type: Other
  description: Control group 24 male, sex and mental age matched controls, aged > 3 to < 8 years
  arm group label: Typically developed children
  arm group type: Other
  description: Control group 80 typically developed children aged > 3 to < 8 years, which corresponds to the mental age of CTD patients.
  40 children aged > 3 to < 5 years, and 40 children aged > 6 to < 8 years will perform the newly developed outcome measures.
  intervention type: Other
  intervention name: Clinical endpoints
  description: Number of epileptic seizures
  Change in antiepileptic treatment (increase or decrease)
  Visual analogical scale on a target symptom defined with the parents,
  CGI,
  Actimetry data over 24 hours,
  Podometry data over 24 hours,
  6 minutes' walk test,
  Clinical examination
  Feasibility of performing an MRI without any anesthesia on a mock scanner
  arm group label: CTD patients
  arm group label: Sex and chronological age matched controls
  intervention type: Other
  intervention name: Parental questionnaires
  description: 10- Adaptive assessment with Vineland Adaptive Behavior scale II,
  11- Mac Arthur questionnaire regarding language,
  12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS),
  13- Dunn sensory profile,
  14- Aberrant Behavior Checklist,
  15- Nisonger Child Behavior Rating form,
  16- Social Responsiveness Scale 2,
  17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)
  arm group label: CTD patients
  arm group label: Sex and mental age matched controls
  arm group label: Typically developed children
  intervention type: Other
  intervention name: Quality of life scale
  description: 18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
  arm group label: CTD patients
  arm group label: Sex and chronological age matched controls
  arm group label: Sex and mental age matched controls
  arm group label: Typically developed children
  intervention type: Other
  intervention name: Cognitive assessments
  description: 19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
  20- CPM-BF
  21- Simple reasoning task on tablet (match-to-sample task)
  22- Implicit rules learning (modified Brixton),
  23- 4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
  24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
  25- Elementary visuo-spatial perception (on tablets)
  arm group label: CTD patients
  arm group label: Sex and chronological age matched controls
  arm group label: Sex and mental age matched controls
  arm group label: Typically developed children
  intervention type: Other
  intervention name: Language assessments
  description: 26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments),
  27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary),
  28- Automatic language analysis (during a 10 minutes interaction, play).
  arm group label: CTD patients
  arm group label: Sex and chronological age matched controls
  arm group label: Sex and mental age matched controls
  arm group label: Typically developed children
  intervention type: Other
  intervention name: Motor assessments
  description: 29- Kinematic task (specifically designed),
  30- Purdue-Pegboard test,
  31- Renzi test
  arm group label: CTD patients
  arm group label: Sex and chronological age matched controls
  arm group label: Sex and mental age matched controls
  arm group label: Typically developed children
  intervention type: Other
  intervention name: Social assessments
  description: 32- Eye-tracking analysis of social visual scenes and social preference index (movies),
  33- theory of mind assessment,
  34- ADOS scale (Autism Spectrum Disorder),
  35- sensitivity to inequality,
  36- pro-social behaviors (help of the psychologist)
  arm group label: CTD patients
  arm group label: Sex and chronological age matched controls
  arm group label: Sex and mental age matched controls
  arm group label: Typically developed children
  intervention type: Other
  intervention name: 3T MRI
  description: 37- Structural, metabolic and functional data
  arm group label: CTD patients
  arm group label: Sex and chronological age matched controls
  intervention type: Other
  intervention name: Cardiac assessments
  description: 38- ECG
  39- Ultrasound
  arm group label: CTD patients
  intervention type: Other
  intervention name: Biological collection
  description: 40- Blood sample
  41- Urinary sample
  42- Superficial skin biopsy
  arm group label: CTD patients
  criteria: 
  gender: All
  minimum age: 3 Years
  maximum age: 35 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Aurore CURIE, MD,PhD
  phone: 06 70 62 69 76
  phone ext: +33
  email: aurore.curie@chu-lyon.fr
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: France
  responsible party type: Sponsor
  sharing ipd: No