<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/NCT01723787</url>
  </required_header>
  <id_info>
    <org_study_id>12-0482</org_study_id>
    <nct_id>NCT01723787</nct_id>
  </id_info>
  <brief_title>Genetic Studies in Patients and Families With Infantile Spasms</brief_title>
  <official_title>Genetic Studies in Patients and Families With Infantile Spasms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Infantile spasms (IIS), a characteristic epilepsy syndrome of infancy with often catastrophic&#xD;
      developmental consequences, is known in some patients to have many different genetic,&#xD;
      metabolic and structural etiologies. However, for most patients IIS is the only presenting&#xD;
      clinical feature and the specific cause is unknown. Only two FDA approved pharmacologic&#xD;
      treatments for IIS exist, Adrenocorticotropic hormone (ACTH) and vigabatrin. While vigabatrin&#xD;
      may be the treatment of choice for Tuberous Sclerosis as a cause for IS, ACTH is the&#xD;
      treatment of choice for all others. Unfortunately, a substantial number of patients may still&#xD;
      not respond to ACTH and there is no a priori way that suggests which patients may be&#xD;
      responders. This has led to the following key questions:&#xD;
&#xD;
      Can novel genetic analyses determine known genetic causes of IS with greater efficiency (more&#xD;
      timely and cost-effective)? Can novel genetic analyses determine previously unknown disease&#xD;
      modifying genes that predispose individuals to develop IS? Can novel genetic analyses&#xD;
      elaborate genes and gene polymorphisms that favor ACTH responsiveness? Do these polymorphisms&#xD;
      suggest strategies to improve ACTH responsiveness?&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Aim 1: Apply whole-exome sequencing to determine possible causes of cryptogenic IS&#xD;
      and evaluate adding whole-exome sequencing to standard practice for determining causes of IS.&#xD;
      Sub-aim 1: Determine the effectiveness of whole-exome sequencing in suggesting&#xD;
      disease-modifying genes that may contribute to triggering IS.&#xD;
&#xD;
      Primary Aim 2: Determine genes, through whole-exome sequencing, that may play a role in&#xD;
      determining ACTH responsiveness for IS. Sub-aim 2: Correlate genes or genetic factors&#xD;
      (haplotypes) associated with ACTH responsiveness and disease modification.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">November 30, 2018</completion_date>
  <primary_completion_date type="Actual">March 9, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Family-Based</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Determine the effectiveness of novel genetic analyses in suggesting disease-modifying genes that may contribute to triggering IIS.</measure>
    <time_frame>Results of the DNA studies will be evaluated prior to completion of the 5th year to assess the need for further investigations.</time_frame>
    <description>Apply novel genetic analyses to determine possible causes of cryptogenic IIS and evaluate adding novel genetic analyses to standard practice for determining causes of IIS</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine genes, through novel genetic analyses, that may play a role in determining ACTH responsiveness for IIS</measure>
    <time_frame>Results of the DNA studies will be evaluated prior to completion of the 5th year to assess the need for further investigations</time_frame>
    <description>Correlate genes or genetic factors (haplotypes) associated with ACTH responsiveness and disease modification</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">63</enrollment>
  <condition>Infantile Spasms</condition>
  <arm_group>
    <arm_group_label>Infantile Spasms</arm_group_label>
    <description>Participants retrospectively identified to have been treated with ACTH according to FDA-approved protocol for Infantile Spasms</description>
  </arm_group>
  <arm_group>
    <arm_group_label>biological parents</arm_group_label>
    <description>Biological parents of participants retrospectively identified to have been treated with ACTH according to FDA-approved protocol for Infantile Spasms</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood, saliva, buccal cells,urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All patients trios (both parents + patient with IIS = trio) with IIS retrospectively&#xD;
        identified to have been treated with ACTH according to FDA-approved protocol will be&#xD;
        eligible for inclusion in this study regardless of age, sex, ethnicity/race, or&#xD;
        socioeconomic status. The principal recruitment venues will be Neurology clinics,&#xD;
        in-patient service and Medical Genetics Clinics at Children's Hospital Colorado and&#xD;
        University of Colorado Health Sciences Center (UCHSC)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient trios (both biological parents + patient with IIS = trio) with IIS&#xD;
             retrospectively identified to have been treated with ACTH according to FDA-approved&#xD;
             protocol (Table 1).&#xD;
&#xD;
          -  Ability to provide informed consent (in case of severe to profound intellectual&#xD;
             disability, consent provided by an legally authorized representative, as necessary)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  IIS due to suspected or genetically proven tuberous sclerosis&#xD;
&#xD;
          -  IIS but do not meet retrospective enrollment criteria (Table 1)&#xD;
&#xD;
          -  Inability to complete consent process&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>31 Days</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim Benke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Colorado</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>November 6, 2012</study_first_submitted>
  <study_first_submitted_qc>November 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 8, 2012</study_first_posted>
  <last_update_submitted>June 10, 2021</last_update_submitted>
  <last_update_submitted_qc>June 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spasm</mesh_term>
    <mesh_term>Spasms, Infantile</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/NCT01723787
org study id: 12-0482
nct id: NCT01723787
lead sponsor: 
has dmc: No
Infantile spasms (IIS), a characteristic epilepsy syndrome of infancy with often catastrophic
      developmental consequences, is known in some patients to have many different genetic,
      metabolic and structural etiologies. However, for most patients IIS is the only presenting
      clinical feature and the specific cause is unknown. Only two FDA approved pharmacologic
      treatments for IIS exist, Adrenocorticotropic hormone (ACTH) and vigabatrin. While vigabatrin
      may be the treatment of choice for Tuberous Sclerosis as a cause for IS, ACTH is the
      treatment of choice for all others. Unfortunately, a substantial number of patients may still
      not respond to ACTH and there is no a priori way that suggests which patients may be
      responders. This has led to the following key questions:

      Can novel genetic analyses determine known genetic causes of IS with greater efficiency (more
      timely and cost-effective)? Can novel genetic analyses determine previously unknown disease
      modifying genes that predispose individuals to develop IS? Can novel genetic analyses
      elaborate genes and gene polymorphisms that favor ACTH responsiveness? Do these polymorphisms
      suggest strategies to improve ACTH responsiveness?
Primary Aim 1: Apply whole-exome sequencing to determine possible causes of cryptogenic IS
      and evaluate adding whole-exome sequencing to standard practice for determining causes of IS.
      Sub-aim 1: Determine the effectiveness of whole-exome sequencing in suggesting
      disease-modifying genes that may contribute to triggering IS.

      Primary Aim 2: Determine genes, through whole-exome sequencing, that may play a role in
      determining ACTH responsiveness for IS. Sub-aim 2: Correlate genes or genetic factors
      (haplotypes) associated with ACTH responsiveness and disease modification.
observational model: Family-Based
time perspective: Prospective
measure: Determine the effectiveness of novel genetic analyses in suggesting disease-modifying genes that may contribute to triggering IIS.
time frame: Results of the DNA studies will be evaluated prior to completion of the 5th year to assess the need for further investigations.
description: Apply novel genetic analyses to determine possible causes of cryptogenic IIS and evaluate adding novel genetic analyses to standard practice for determining causes of IIS
measure: Determine genes, through novel genetic analyses, that may play a role in determining ACTH responsiveness for IIS
time frame: Results of the DNA studies will be evaluated prior to completion of the 5th year to assess the need for further investigations
description: Correlate genes or genetic factors (haplotypes) associated with ACTH responsiveness and disease modification
arm group label: Infantile Spasms
description: Participants retrospectively identified to have been treated with ACTH according to FDA-approved protocol for Infantile Spasms
arm group label: biological parents
description: Biological parents of participants retrospectively identified to have been treated with ACTH according to FDA-approved protocol for Infantile Spasms
blood, saliva, buccal cells,urine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 31 Days
maximum age: 21 Years
healthy volunteers: No
last name: Tim Benke, MD
role: Principal Investigator
affiliation: Children's Hospital Colorado
facility: 
country: United States
responsible party type: Sponsor
mesh term: Spasm
mesh term: Spasms, Infantile