<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/NCT02228915</url>
  </required_header>
  <id_info>
    <org_study_id>14-1780</org_study_id>
    <nct_id>NCT02228915</nct_id>
  </id_info>
  <brief_title>Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis</brief_title>
  <acronym>SOD1</acronym>
  <official_title>Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to discover and quantitate the differences in&#xD;
      post-translational modifications found in the Cu, Zn superoxide dismutase (SOD1) of patients&#xD;
      with amyotrophic lateral sclerosis (ALS) as compared to healthy individuals. SOD1 is a known&#xD;
      genetic cause of ALS. With certain mutations, SOD1 gains a toxic function which leads to&#xD;
      motor neuron death.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease in which&#xD;
      mutations in human Cu, Zn Superoxide Dismutase (SOD1) have been identified as a cause of&#xD;
      familial ALS (FALS) cases.1-2 It has been shown that mutant SOD1 develops a novel toxic&#xD;
      function through experiments demonstrating that many disease mutants maintain enzymatic&#xD;
      activity, SOD1-null mice do not exhibit ALS symptoms, and co-expressed wild type protein does&#xD;
      not rescue the disease-state.7-11 The majority of cases, however, are not caused directly by&#xD;
      mutations of SOD1, instead being caused by a poorly understood interplay of several genes as&#xD;
      well as environmental factors, which is often referred to as sporadic ALS (SALS).3 It has&#xD;
      been found that FALS and SALS share similar pathology. 4-6 The hSOD1 protein aggregates&#xD;
      characteristic of FALS have also been found in SALS patients, furthering the evidence that&#xD;
      hSOD1 has an important role in the etiology of ALS in sporadic ALS patients.16-19 The exact&#xD;
      mechanism of SOD1-associated toxicity has not yet been elucidated though many disease mutants&#xD;
      have been shown to destabilize the SOD1 dimer. In this study we aim to compare the levels of&#xD;
      SOD1 post-tra slational modifications in ALS patients to levels in healthy donors and to&#xD;
      determine if there are distinct patterns of protein glutathionylation or phosphorylation. Our&#xD;
      overall goal is to elucidate a direct mechanism of toxicity in SALS as well as identify&#xD;
      potentially critical triggers&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">October 16, 2018</completion_date>
  <primary_completion_date type="Actual">October 14, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Post-translational modifications (PTMs) of Cu/Zn superoxide dismutase 1</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <enrollment type="Actual">21</enrollment>
  <condition>ALS</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      A portion of this sample will be stored for future use in study of ALS and how the critical&#xD;
      protien affects the disease progression long term. This sample will be stored de-identified;&#xD;
      therefore will not be linked to any identifying informaton about the subject. Sample will be&#xD;
      stored at the UNC biophysics and Biochemistry lab indefinitely&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        SALS patients SOD1 associated FALS patients Healthy control&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  SALS patients&#xD;
&#xD;
          -  SOD1 associated FALS patients&#xD;
&#xD;
          -  Healthy control&#xD;
&#xD;
        Exclusion Criteria: none&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chafic Karam, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nikolay V Dokholyan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UNC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UNC Neurology ALS clinic</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2014</study_first_posted>
  <last_update_submitted>October 16, 2018</last_update_submitted>
  <last_update_submitted_qc>October 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 17, 2018</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>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02228915
org study id: 14-1780
nct id: NCT02228915
lead sponsor: 
has dmc: No
The purpose of this research study is to discover and quantitate the differences in
      post-translational modifications found in the Cu, Zn superoxide dismutase (SOD1) of patients
      with amyotrophic lateral sclerosis (ALS) as compared to healthy individuals. SOD1 is a known
      genetic cause of ALS. With certain mutations, SOD1 gains a toxic function which leads to
      motor neuron death.
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease in which
      mutations in human Cu, Zn Superoxide Dismutase (SOD1) have been identified as a cause of
      familial ALS (FALS) cases.1-2 It has been shown that mutant SOD1 develops a novel toxic
      function through experiments demonstrating that many disease mutants maintain enzymatic
      activity, SOD1-null mice do not exhibit ALS symptoms, and co-expressed wild type protein does
      not rescue the disease-state.7-11 The majority of cases, however, are not caused directly by
      mutations of SOD1, instead being caused by a poorly understood interplay of several genes as
      well as environmental factors, which is often referred to as sporadic ALS (SALS).3 It has
      been found that FALS and SALS share similar pathology. 4-6 The hSOD1 protein aggregates
      characteristic of FALS have also been found in SALS patients, furthering the evidence that
      hSOD1 has an important role in the etiology of ALS in sporadic ALS patients.16-19 The exact
      mechanism of SOD1-associated toxicity has not yet been elucidated though many disease mutants
      have been shown to destabilize the SOD1 dimer. In this study we aim to compare the levels of
      SOD1 post-tra slational modifications in ALS patients to levels in healthy donors and to
      determine if there are distinct patterns of protein glutathionylation or phosphorylation. Our
      overall goal is to elucidate a direct mechanism of toxicity in SALS as well as identify
      potentially critical triggers
observational model: Cohort
time perspective: Prospective
measure: Post-translational modifications (PTMs) of Cu/Zn superoxide dismutase 1
time frame: 6 months
A portion of this sample will be stored for future use in study of ALS and how the critical
      protien affects the disease progression long term. This sample will be stored de-identified;
      therefore will not be linked to any identifying informaton about the subject. Sample will be
      stored at the UNC biophysics and Biochemistry lab indefinitely
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Chafic Karam, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
last name: Nikolay V Dokholyan, PhD
role: Principal Investigator
affiliation: UNC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
sharing ipd: Undecided