<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/NCT01661855</url>
  </required_header>
  <id_info>
    <org_study_id>RILISE-07-2013</org_study_id>
    <nct_id>NCT01661855</nct_id>
  </id_info>
  <brief_title>A Pilot Study of Riluzole Versus Placebo in the Treatment of Children and Adolescents With ASD</brief_title>
  <acronym>RILISE</acronym>
  <official_title>A Pilot Study of Riluzole vs. Placebo in the Treatment of Children and Adolescents With Autism Spectrum Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Evdokia Anagnostou</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Holland Bloorview Kids Rehabilitation Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>McMaster University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Western Ontario, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Unity Health Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Anagnostou, Evdokia, M.D.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will examine the potential efficacy and safety of riluzole for core and associated&#xD;
      symptom domains of autism and will explore biological markers of safety and treatment&#xD;
      response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are no pharmacologic treatments available for social function deficits in individuals&#xD;
      with Autism Spectrum Disorders (ASD). The data for pharmacologic treatment of repetitive&#xD;
      behaviors in this disorder has also become difficult to interpret given that the last two&#xD;
      large multisite trials of selective serotonin reuptake inhibitors (SSRIs) in autism are&#xD;
      reported to be negative for the treatment of repetitive behaviors. Only the associated&#xD;
      symptom of irritability has 2 drugs with FDA indications whereas no systematic data exists on&#xD;
      the pharmacologic treatment of anxiety in ASD, and response to rates to stimulants for&#xD;
      hyperactivity are lower than what is seen in attention deficit hyperactivity disorder (ADHD).&#xD;
      In addition, there are no biological markers of treatment response identified in this&#xD;
      population at this point. This study will examine the potential efficacy and safety of&#xD;
      riluzole for core and associated symptom domains of autism and will explore biological&#xD;
      markers of safety and treatment response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy of riluzole vs. placebo on measures of social function</measure>
    <time_frame>12 weeks</time_frame>
    <description>This will be measured by the Aberrant Behavior Checklist (ABC) - Lethargy / Social Withdrawal Subscale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy of riluzole vs. placebo on measures of repetitive behaviors</measure>
    <time_frame>12 weeks</time_frame>
    <description>This will be measured by the Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy of riluzole vs. placebo on measures of repetitive behaviors</measure>
    <time_frame>12 weeks</time_frame>
    <description>This will be measured by the Repetitive Behavior Scale (RBS-R)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of riluzole in children and adolescents with ASD</measure>
    <time_frame>12 Weeks</time_frame>
    <description>This will be measured by the Safety Monitoring Uniform Report Form (SMURF)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of riluzole in children and adolescents with ASD</measure>
    <time_frame>12 Weeks</time_frame>
    <description>This will be measured by the Clinical Global Impressions - Improvement Scale - Global (CGI-I-Global)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Autism Spectrum Disorders</condition>
  <arm_group>
    <arm_group_label>Riluzole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Riluzole</intervention_name>
    <description>50mg once daily (QD) for 12 weeks for participants 6-11 years old; 50mg twice daily (BID) for 12 weeks for participants 12-17 years old</description>
    <arm_group_label>Riluzole</arm_group_label>
    <other_name>Rilutek</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo comparator once daily (QD) for 12 weeks for participants 6-11 years old; Placebo comparator twice daily (BID) for 12 weeks for participants 12-17 years old</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female outpatients 6-17 years of age inclusive, with a mental age equivalent ≥&#xD;
             18 months at Screening visit.&#xD;
&#xD;
          2. Meet Diagnostic and Statistical Manual (DSM-IV) criteria for an ASD.&#xD;
&#xD;
          3. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at&#xD;
             Screening.&#xD;
&#xD;
          4. If already receiving stable interventions must meet the following criteria:&#xD;
&#xD;
               1. If already receiving stable concomitant medications affecting behavior, must be&#xD;
                  on a stable dose during the preceding 1 month prior to Screening (with the&#xD;
                  exception of fluoxetine, where a period of 6 weeks is needed), and will not&#xD;
                  electively initiate new or modify ongoing medications for study duration.&#xD;
&#xD;
               2. If already receiving stable non-pharmacological educational, behavioral, and/or&#xD;
                  dietary interventions, have continuous participation during the preceding 3&#xD;
                  months prior to Screening, and not electively initiate new or modify ongoing&#xD;
                  interventions for the duration of the study.&#xD;
&#xD;
          5. Have normal physical examination and laboratory test results at Screening. If&#xD;
             abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.&#xD;
&#xD;
          6. Ability to complete assessments- fluency in English (parent; patient, if verbal).&#xD;
&#xD;
          7. Consent to participate in the Province of Ontario Neurodevelopmental (POND) study and&#xD;
             commitment to completing as many stages as possible of the phenotyping measures&#xD;
             (Stages 1, 2 and 3), genomics component, and interest in being imaged through POND.&#xD;
&#xD;
          8. Ability to obtain written informed consent from the participant, if developmentally&#xD;
             appropriate. If a participant does not have the capacity to consent, ability to obtain&#xD;
             assent (if developmentally appropriate), as well as written informed consent from&#xD;
             their parent(s)/legal guardian.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant female patients; sexually active female patients on inadequate birth control.&#xD;
&#xD;
          2. Patients with a serious medical condition that, based on Investigator judgment, might&#xD;
             interfere with the conduct of the study, confound interpretation of the study results,&#xD;
             or endanger their own well-being. Patients with evidence or history of malignancy or&#xD;
             any significant hematological, endocrine, cardiovascular (including any rhythm&#xD;
             disorder), respiratory, renal, hepatic, or gastrointestinal disease, not including&#xD;
             mild common pediatric diseases in these areas that are stable (e.g. mild asthma,&#xD;
             constipation, etc.).&#xD;
&#xD;
          3. Patients with unstable epilepsy (i.e. seizures occurring within the last 6 months), or&#xD;
             patients with epilepsy who are not on stable doses of antiepileptic medications (i.e.&#xD;
             dose changes within the last 3 months).&#xD;
&#xD;
          4. Patients with hypersensitivity to riluzole or any components of its formulation.&#xD;
&#xD;
          5. Patients with one or more of the following: HIV, Hepatitis B virus, Hepatitis C virus,&#xD;
             hemophilia (bleeding problems, recent nose and brain injuries), abnormal blood&#xD;
             pressure (hypotension or hypertension), drug abuse, immunity disorder, major&#xD;
             depressive episode or psychosis.&#xD;
&#xD;
          6. Patients unable to tolerate venipuncture procedures for blood sampling.&#xD;
&#xD;
          7. Patients receiving concomitant medications that specifically target the glutamate&#xD;
             system (e.g. memantine, d-cycloserine), or decrease the elimination of riluzole (e.g.&#xD;
             theophylline, quinolones), less than 30 days prior to the screening visit.&#xD;
&#xD;
          8. Patients actively enrolled in another intervention study.&#xD;
&#xD;
          9. Patients who are unable to swallow pills.&#xD;
&#xD;
         10. Patients who have elevated liver enzymes ≥ 3 times the normal amount before the study&#xD;
             begins.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Evdokia Anagnostou, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Holland Bloorview Kids Rehabilitation Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert Nicolson, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Western Ontario, Lawson Health Research Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Terry Bennett, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University; Offord Centre for Child Studies</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Offord Centre for Child Studies</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8S 4K1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lawson Health Research Institute</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5W9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holland Bloorview Kids Rehabilitation Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4G 1R8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>July 26, 2012</study_first_submitted>
  <study_first_submitted_qc>August 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 10, 2012</study_first_posted>
  <last_update_submitted>March 17, 2017</last_update_submitted>
  <last_update_submitted_qc>March 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Anagnostou, Evdokia, M.D.</investigator_affiliation>
    <investigator_full_name>Evdokia Anagnostou</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Autism Spectrum Disorders</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
    <mesh_term>Child Development Disorders, Pervasive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Riluzole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01661855
org study id: RILISE-07-2013
nct id: NCT01661855
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This study will examine the potential efficacy and safety of riluzole for core and associated
      symptom domains of autism and will explore biological markers of safety and treatment
      response.
There are no pharmacologic treatments available for social function deficits in individuals
      with Autism Spectrum Disorders (ASD). The data for pharmacologic treatment of repetitive
      behaviors in this disorder has also become difficult to interpret given that the last two
      large multisite trials of selective serotonin reuptake inhibitors (SSRIs) in autism are
      reported to be negative for the treatment of repetitive behaviors. Only the associated
      symptom of irritability has 2 drugs with FDA indications whereas no systematic data exists on
      the pharmacologic treatment of anxiety in ASD, and response to rates to stimulants for
      hyperactivity are lower than what is seen in attention deficit hyperactivity disorder (ADHD).
      In addition, there are no biological markers of treatment response identified in this
      population at this point. This study will examine the potential efficacy and safety of
      riluzole for core and associated symptom domains of autism and will explore biological
      markers of safety and treatment response.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Efficacy of riluzole vs. placebo on measures of social function
time frame: 12 weeks
description: This will be measured by the Aberrant Behavior Checklist (ABC) - Lethargy / Social Withdrawal Subscale
measure: Efficacy of riluzole vs. placebo on measures of repetitive behaviors
time frame: 12 weeks
description: This will be measured by the Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS)
measure: Efficacy of riluzole vs. placebo on measures of repetitive behaviors
time frame: 12 weeks
description: This will be measured by the Repetitive Behavior Scale (RBS-R)
measure: Safety and tolerability of riluzole in children and adolescents with ASD
time frame: 12 Weeks
description: This will be measured by the Safety Monitoring Uniform Report Form (SMURF)
measure: Safety and tolerability of riluzole in children and adolescents with ASD
time frame: 12 Weeks
description: This will be measured by the Clinical Global Impressions - Improvement Scale - Global (CGI-I-Global)
arm group label: Riluzole
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Riluzole
description: 50mg once daily (QD) for 12 weeks for participants 6-11 years old; 50mg twice daily (BID) for 12 weeks for participants 12-17 years old
arm group label: Riluzole
other name: Rilutek
intervention type: Drug
intervention name: Placebo
description: Placebo comparator once daily (QD) for 12 weeks for participants 6-11 years old; Placebo comparator twice daily (BID) for 12 weeks for participants 12-17 years old
arm group label: Placebo
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: No
last name: Evdokia Anagnostou, M.D.
role: Principal Investigator
affiliation: Holland Bloorview Kids Rehabilitation Hospital
last name: Robert Nicolson, M.D.
role: Principal Investigator
affiliation: University of Western Ontario, Lawson Health Research Institute
last name: Terry Bennett, M.D.
role: Principal Investigator
affiliation: McMaster University; Offord Centre for Child Studies
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor-Investigator
investigator affiliation: Anagnostou, Evdokia, M.D.
investigator full name: Evdokia Anagnostou
investigator title: Principal Investigator
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive
mesh term: Riluzole
sharing ipd: No