<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/NCT03812055</url>
  </required_header>
  <id_info>
    <org_study_id>18-LDRTC-02</org_study_id>
    <nct_id>NCT03812055</nct_id>
  </id_info>
  <brief_title>Cellular Pharmacodynamics of Small Molecules in Lysosomal Storage Disorders</brief_title>
  <official_title>Cellular Pharmacodynamics of Small Molecules in Sanfilippo Disease(s) (MPS3) and Other Lysosomal Storage Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lysosomal and Rare Disorders Research and Treatment Center, Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lysosomal and Rare Disorders Research and Treatment Center, Inc.</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>
      The purpose of this study is to evaluate the effect of small molecule therapy in primary&#xD;
      cells derived from patients with lysosomal storage disease. The study will focus on activity&#xD;
      of small molecules, in terms of measurements enzymes activity and level of substrates&#xD;
      accumulations. Also, the effects of small molecules on cell function, including&#xD;
      autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be&#xD;
      investigated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lysosomal storage diseases (LSD) often cause severe disability and have a devastating effect&#xD;
      on quality of life. The current standard of care of a majority of LSD is enzyme replacement&#xD;
      therapy (ERT). ERT, however, becomes less effective during the advanced stages of a disease.&#xD;
      Another therapy is substrate reduction therapy (SRT). For example, SRT therapy for Gaucher&#xD;
      disease with small molecules acts on ceramide synthesis pathway by decreasing production of&#xD;
      the substrate. But, none of the above therapies are effective for treatment of a neuropathic&#xD;
      form of LSD. Neurodegenerative changes in the central nervous system are a major problem in&#xD;
      Sanfilippo disease. They cause severe disability and behavioral disturbance. This is the main&#xD;
      reason for the absence of therapeutic options for MPS3 (Sanfilippo) patients. The future of&#xD;
      neuropathic form of LSD therapy may lie in small molecules acting as agents for&#xD;
      enzyme-enhancement therapy (EET). EET is based on the ability of small molecules to fold the&#xD;
      misfolded mutant enzyme, activate autophagy-lysosomal pathways or mitochondrial function.&#xD;
      This treatment approach has the potential to cross the CNS and carries the potential to treat&#xD;
      the neurological symptoms of Sanfilippo disease or other types of LSD.&#xD;
&#xD;
      The purpose of this study will evaluate the effect of small molecule therapy in primary cells&#xD;
      derived from patients with lysosomal storage disease. The study will be focused on activity&#xD;
      of small molecules, in terms of measurements enzymes activity and level of substrates&#xD;
      accumulations. Also, the effects of small molecules on cell function, including&#xD;
      autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be&#xD;
      investigated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 6, 2018</start_date>
  <completion_date type="Anticipated">July 2020</completion_date>
  <primary_completion_date type="Anticipated">July 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Effect on enzyme activity</measure>
    <time_frame>24 months</time_frame>
    <description>To evaluate the effect of small molecules on level of enzyme activity in primary cells derived from patients using fluorometric enzyme assays.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect on substrate accumulation</measure>
    <time_frame>24 months</time_frame>
    <description>To evaluate the effect of small molecules on heparin sulfate accumulation and substrate accumulation in primary cells derived from patients using techniques like ELISA and mass spectrometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect on autophagy-lysosomal pathway</measure>
    <time_frame>24 months</time_frame>
    <description>To evaluate the effect of small molecules on autophagy-lysosomal functions in primary cells derived from patients using commercially available assays</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect on mitochondrial functions</measure>
    <time_frame>24 months</time_frame>
    <description>To evaluate the effect of small molecules on energy metabolism and mitochondrial functions in primary cells derived from patients using commercially available assay kits</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect on immune and inflammatory response</measure>
    <time_frame>24 months</time_frame>
    <description>Examine the immune and inflammatory response to treatment with small molecules using flow cytometry based immunophenotyping</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Lysosomal Storage Diseases</condition>
  <arm_group>
    <arm_group_label>LSD</arm_group_label>
    <description>Subjects diagnosed or suspected to have any of the following lysosomal storage diseases: Gaucher disease, Fabry disease, Pompe disease, Mucopolysaccharidoses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>Subjects with no known lysosomal storage disorder</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients diagnosed or suspected of having a lysosomal storage disorder and family members&#xD;
        of diagnosed patients will be recruited. Informed consent will be obtained prior to the&#xD;
        execution of any research procedures.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects with&#xD;
&#xD;
          1. confirmed diagnosis of any lysosomal storage disorder&#xD;
&#xD;
          2. family members with history of lysosomal storage disorders&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects excluded from the study include those who:&#xD;
&#xD;
          1. present with severe cognitive deficits impairing decision making&#xD;
&#xD;
          2. are unable to or for whom it is medically unsafe to withdraw from their current&#xD;
             medications, such as subjects on SSRI s and other psychoactive drugs. The subjects on&#xD;
             SSRIs may be included in the study only with an approval from the prescribing&#xD;
             physician to discontinue their medications temporarily for the study.&#xD;
&#xD;
          3. are pregnant or nursing. All women of child bearing potential will undergo a pregnancy&#xD;
             test.&#xD;
&#xD;
          4. have a history of neurologic conditions such as stroke or any focal brain lesion that&#xD;
             may result in parkinonian manifestations. Individuals with such MRI findings will be&#xD;
             excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Margarita M Ivanova, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LDRTC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ozlem Goker-Alpan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LDRTC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Renuka Limgala, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LDRTC</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Margarita M Ivanova, PhD</last_name>
    <phone>7032616220</phone>
    <email>mivanova@ldrtc.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Uyensa Beese</last_name>
    <phone>7032616220</phone>
    <email>ubeese@ldrtc.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>LDRTC</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Margarita Ivanova, PhD</last_name>
      <phone>703-261-6220</phone>
      <email>mivanova@ldrtc.org</email>
    </contact>
    <contact_backup>
      <last_name>Ozlem M Goker-Alpan, MD</last_name>
      <phone>7032616220</phone>
      <email>ogokar-alpan@ldrtc.org</email>
    </contact_backup>
    <investigator>
      <last_name>Ozlem Goker-Alpan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Margarita M Ivanova, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Renuka Limgala, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.ldrtc.org</url>
    <description>Institute website for more details</description>
  </link>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>January 18, 2019</last_update_submitted>
  <last_update_submitted_qc>January 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</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>Lysosomal Storage Diseases</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/NCT03812055
org study id: 18-LDRTC-02
nct id: NCT03812055
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the effect of small molecule therapy in primary
      cells derived from patients with lysosomal storage disease. The study will focus on activity
      of small molecules, in terms of measurements enzymes activity and level of substrates
      accumulations. Also, the effects of small molecules on cell function, including
      autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be
      investigated.
Lysosomal storage diseases (LSD) often cause severe disability and have a devastating effect
      on quality of life. The current standard of care of a majority of LSD is enzyme replacement
      therapy (ERT). ERT, however, becomes less effective during the advanced stages of a disease.
      Another therapy is substrate reduction therapy (SRT). For example, SRT therapy for Gaucher
      disease with small molecules acts on ceramide synthesis pathway by decreasing production of
      the substrate. But, none of the above therapies are effective for treatment of a neuropathic
      form of LSD. Neurodegenerative changes in the central nervous system are a major problem in
      Sanfilippo disease. They cause severe disability and behavioral disturbance. This is the main
      reason for the absence of therapeutic options for MPS3 (Sanfilippo) patients. The future of
      neuropathic form of LSD therapy may lie in small molecules acting as agents for
      enzyme-enhancement therapy (EET). EET is based on the ability of small molecules to fold the
      misfolded mutant enzyme, activate autophagy-lysosomal pathways or mitochondrial function.
      This treatment approach has the potential to cross the CNS and carries the potential to treat
      the neurological symptoms of Sanfilippo disease or other types of LSD.

      The purpose of this study will evaluate the effect of small molecule therapy in primary cells
      derived from patients with lysosomal storage disease. The study will be focused on activity
      of small molecules, in terms of measurements enzymes activity and level of substrates
      accumulations. Also, the effects of small molecules on cell function, including
      autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be
      investigated.
observational model: Case-Only
time perspective: Prospective
measure: Effect on enzyme activity
time frame: 24 months
description: To evaluate the effect of small molecules on level of enzyme activity in primary cells derived from patients using fluorometric enzyme assays.
measure: Effect on substrate accumulation
time frame: 24 months
description: To evaluate the effect of small molecules on heparin sulfate accumulation and substrate accumulation in primary cells derived from patients using techniques like ELISA and mass spectrometry
measure: Effect on autophagy-lysosomal pathway
time frame: 24 months
description: To evaluate the effect of small molecules on autophagy-lysosomal functions in primary cells derived from patients using commercially available assays
measure: Effect on mitochondrial functions
time frame: 24 months
description: To evaluate the effect of small molecules on energy metabolism and mitochondrial functions in primary cells derived from patients using commercially available assay kits
measure: Effect on immune and inflammatory response
time frame: 24 months
description: Examine the immune and inflammatory response to treatment with small molecules using flow cytometry based immunophenotyping
arm group label: LSD
description: Subjects diagnosed or suspected to have any of the following lysosomal storage diseases: Gaucher disease, Fabry disease, Pompe disease, Mucopolysaccharidoses.
arm group label: Control
description: Subjects with no known lysosomal storage disorder
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Margarita M Ivanova, PhD
role: Principal Investigator
affiliation: LDRTC
last name: Ozlem Goker-Alpan, MD
role: Principal Investigator
affiliation: LDRTC
last name: Renuka Limgala, PhD
role: Principal Investigator
affiliation: LDRTC
last name: Margarita M Ivanova, PhD
phone: 7032616220
email: mivanova@ldrtc.org
last name: Uyensa Beese
phone: 7032616220
email: ubeese@ldrtc.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: United States
url: http://www.ldrtc.org
description: Institute website for more details
responsible party type: Sponsor
mesh term: Lysosomal Storage Diseases
sharing ipd: Undecided