<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/NCT04417023</url>
  </required_header>
  <id_info>
    <org_study_id>B3forNMD</org_study_id>
    <nct_id>NCT04417023</nct_id>
  </id_info>
  <brief_title>B3 for NMD: Bench to Bedside and Back</brief_title>
  <official_title>B3 for NMD: Bench to Bedside and Back - Transformative Discoveries Leading to Improved Care in Neuromuscular Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ottawa Hospital Research Institute</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>
      Background: Neuromuscular diseases (NMD) represent a broad group of rare genetic and acquired&#xD;
      disorders, affecting over 300,000 people in Canada. Given the multiple different NMD&#xD;
      subtypes, almost half of patients with NMD remain undiagnosed.&#xD;
&#xD;
      Objective: The purpose of this study is to identify genetic or other markers in patient&#xD;
      biosamples (e.g. blood, muscle, skin samples), electrodiagnostic studies or imaging that may&#xD;
      help physicians and scientists provide faster ways to diagnose patients with NMD, study&#xD;
      disease progression, and discover underlying disease mechanisms that may lead to future NMD&#xD;
      therapies.&#xD;
&#xD;
      Eligibility: Adults with NMD&#xD;
&#xD;
      Design: Participants will have blood and/or tissue samples, and data from clinical&#xD;
      information, imaging, and electrodiagnostic studies collected. Sample and data collection at&#xD;
      the Neuromuscular Center, The Ottawa Hospital may include blood, DNA, saliva, cerebrospinal&#xD;
      fluid, urine and stool samples, skin or muscle biopsy, and routine diagnostic imaging studies&#xD;
      such as electrodiagnostic studies, ultrasound, and magnetic resonance imaging.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The B3 for NMD creates a streamlined approach to develop the Bench (preclinical and&#xD;
      laboratory characterization) to Bedside (clinical and imaging assessment) and Back&#xD;
      (biomarker, diagnostics and therapy development) approach to develop transformative therapies&#xD;
      for patients with rare NMDs. This study focuses on assessing current diagnostic techniques&#xD;
      and disease characterization of difficult-to-diagnose NMDs including Motor Neuron Disease&#xD;
      (e.g. ALS), Neuromuscular Junction Disorders, Neuropathies, Myopathies.&#xD;
&#xD;
      Activity 1: Improve Diagnosis: Identification of rare and novel genes causing NMD with next&#xD;
      generation sequencing and develop imaging modalities and biomarkers to aid in diagnosis.&#xD;
&#xD;
      A collaborative research team of clinicians, informaticians, and scientists has been formed&#xD;
      to rapidly identify the genes and the autoimmune antibodies responsible for a wide spectrum&#xD;
      of NMD present in the Canadian population, as well as to explore mechanisms causing these&#xD;
      disorders. In addition, novel genetic and biomarker approaches are needed to facilitate&#xD;
      diagnosis and permit the identification of mutations in novel genes, leading to discovery of&#xD;
      the molecular mechanisms underlying the NMD disease state. Novel diagnostic techniques that&#xD;
      examine thousands of genes (e.g. exome/genome sequencing), protein expression (e.g. RNA&#xD;
      sequencing) and/or serum biomarkers (e.g. exosomes) will be assessed to provide a more rapid&#xD;
      diagnosis for patients with NMD. In addition, imaging characteristics for these rare diseases&#xD;
      (MRI, Muscle/Nerve Ultrasound/nerve conduction studies) need to be assessed and compared in&#xD;
      order to provide an efficient, effective and cost-savings approach to diagnosis for patients&#xD;
      with inherited or sporadic NMD.&#xD;
&#xD;
      Activity 2. Disease Characterization: Identifying pathophysiological mechanisms in NMD&#xD;
&#xD;
      Preclinical research provides the foundation for discoveries that improve lives for patients&#xD;
      with NMD. The identification of cellular and molecular events that govern normal muscle and&#xD;
      nerve differentiation drives the development of regenerative-based therapies, whereas the&#xD;
      characterization of the disease state uncovers new therapeutic targets for disease&#xD;
      intervention. Although many NMDs were previously incurable, recent breakthroughs in the&#xD;
      molecular pathogenesis of monogenic and acquired disorders are now revealing potential&#xD;
      targeted disease-modifying therapies that may improve muscle health and prevent disability.&#xD;
      The goal is to assess clinical samples such as blood, skin/muscle biopsies, cerebrospinal&#xD;
      fluid obtained through collaboration with NMC clinicians and researchers to help develop&#xD;
      effective novel/known drug compounds that may act as promising therapies that, in the future,&#xD;
      can be rapidly moved into local and multicenter clinical trials.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 8, 2019</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To provide a more rapid diagnosis for patients with rare NMD and identify NMD biomarkers.</measure>
    <time_frame>5 years</time_frame>
    <description>Identification of genes responsible for rare genetic NMD diseases, biomarkers, and imaging techniques to aid in diagnosis and disease management.&#xD;
Genetic and Biomarker Samples: 5 to 10 ml of blood or saliva will be collected preferably during routine medical care for DNA extraction. Urine or other bodily fluid collection will be used for biomarker studies. Fibroblast or myoblast samples can be used to establish a cell line. Unaffected family members can also provide tissue samples for DNA extraction or establishment of cell lines that will be stored in the Ottawa Hospital Neuromuscular Biobank.&#xD;
Imaging: Routine diagnostic imaging studies will be analyzed for pattern of involvement: Electrodiagnostic Studies (Nerve Conduction and Electromyogram Studies) will be included to assess nerve and muscle dysfunction, Ultrasound images of affected muscles and nerves, and MRI whole-body scans will be obtained for whole muscle qualitative evaluation and to assess inflammation and edema</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To characterize disease mechanisms to advance potential therapies of tomorrow.</measure>
    <time_frame>5 years</time_frame>
    <description>Disease Characterization: Functional validation of gene candidates&#xD;
Genetic Diagnosis: Disease-causing genetic variants must be proven with genetic or functional data. Biochemical validation of a putative pathological variant to confirm the functional significance of a newly identified mutation can be considered confirmatory in some cases.&#xD;
Biomarker Development: We will use patient-derived material to develop biomarkers using metabolomic, proteomic, and transcriptional profiling. We will perform computational and in vitro screens using system-wide RNA and chemical libraries to look for modifications of disease-specific biomarkers.&#xD;
Sample analysis: We developed a collaborative network of laboratory-based scientists at the Ottawa Hospital Research Institute, University of Ottawa Faculty of Medicine, and the Children's Hospital of Eastern Ontario, and across Canada. This is vital to the validation of gene candidates and biomechanical mechanisms for the diagnosis or rare dis</description>
  </secondary_outcome>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Neuromuscular Disease</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>B3 for NMD: Bench to Bedside and Back</intervention_name>
    <description>Transformative discoveries leading to improved care in Neuromuscular Disease</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole Blood, CSF, Saliva, Skin Biopsy, and Muscle Biospy&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Affected or unaffected cohorts (including genetic carriers or non-carriers as reference&#xD;
        biospecimens&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients or blood relatives of patients classified as having a neuromuscular disease from&#xD;
        the following categories:&#xD;
&#xD;
          -  Motor Neuron Disease (Amyotrophic Lateral Sclerosis/Spinal Muscular Atrophy)&#xD;
&#xD;
          -  Neuropathies&#xD;
&#xD;
          -  Neuromuscular Junction Disorders&#xD;
&#xD;
          -  Myopathies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients referred to the neurology clinic without a neuromuscular disorder:&#xD;
&#xD;
          -  Central nervous system disorders such as Stroke&#xD;
&#xD;
          -  Multiple Sclerosis&#xD;
&#xD;
          -  Parkinson's disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr. Jodi Warman Chardon, MD MSc FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ottawa Hospital Research Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Maria Liezl Vinci Duff</last_name>
    <phone>613-798-5555</phone>
    <phone_ext>19070</phone_ext>
    <email>maduff@ohri.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ottawa Hospital Research Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y4E9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Duff</last_name>
      <phone>613-798</phone>
      <phone_ext>19070</phone_ext>
      <email>maduff@ohri.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>July 6, 2020</last_update_submitted>
  <last_update_submitted_qc>July 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</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>Neuromuscular Diseases</mesh_term>
  </condition_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/NCT04417023
org study id: B3forNMD
nct id: NCT04417023
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background: Neuromuscular diseases (NMD) represent a broad group of rare genetic and acquired
      disorders, affecting over 300,000 people in Canada. Given the multiple different NMD
      subtypes, almost half of patients with NMD remain undiagnosed.

      Objective: The purpose of this study is to identify genetic or other markers in patient
      biosamples (e.g. blood, muscle, skin samples), electrodiagnostic studies or imaging that may
      help physicians and scientists provide faster ways to diagnose patients with NMD, study
      disease progression, and discover underlying disease mechanisms that may lead to future NMD
      therapies.

      Eligibility: Adults with NMD

      Design: Participants will have blood and/or tissue samples, and data from clinical
      information, imaging, and electrodiagnostic studies collected. Sample and data collection at
      the Neuromuscular Center, The Ottawa Hospital may include blood, DNA, saliva, cerebrospinal
      fluid, urine and stool samples, skin or muscle biopsy, and routine diagnostic imaging studies
      such as electrodiagnostic studies, ultrasound, and magnetic resonance imaging.
The B3 for NMD creates a streamlined approach to develop the Bench (preclinical and
      laboratory characterization) to Bedside (clinical and imaging assessment) and Back
      (biomarker, diagnostics and therapy development) approach to develop transformative therapies
      for patients with rare NMDs. This study focuses on assessing current diagnostic techniques
      and disease characterization of difficult-to-diagnose NMDs including Motor Neuron Disease
      (e.g. ALS), Neuromuscular Junction Disorders, Neuropathies, Myopathies.

      Activity 1: Improve Diagnosis: Identification of rare and novel genes causing NMD with next
      generation sequencing and develop imaging modalities and biomarkers to aid in diagnosis.

      A collaborative research team of clinicians, informaticians, and scientists has been formed
      to rapidly identify the genes and the autoimmune antibodies responsible for a wide spectrum
      of NMD present in the Canadian population, as well as to explore mechanisms causing these
      disorders. In addition, novel genetic and biomarker approaches are needed to facilitate
      diagnosis and permit the identification of mutations in novel genes, leading to discovery of
      the molecular mechanisms underlying the NMD disease state. Novel diagnostic techniques that
      examine thousands of genes (e.g. exome/genome sequencing), protein expression (e.g. RNA
      sequencing) and/or serum biomarkers (e.g. exosomes) will be assessed to provide a more rapid
      diagnosis for patients with NMD. In addition, imaging characteristics for these rare diseases
      (MRI, Muscle/Nerve Ultrasound/nerve conduction studies) need to be assessed and compared in
      order to provide an efficient, effective and cost-savings approach to diagnosis for patients
      with inherited or sporadic NMD.

      Activity 2. Disease Characterization: Identifying pathophysiological mechanisms in NMD

      Preclinical research provides the foundation for discoveries that improve lives for patients
      with NMD. The identification of cellular and molecular events that govern normal muscle and
      nerve differentiation drives the development of regenerative-based therapies, whereas the
      characterization of the disease state uncovers new therapeutic targets for disease
      intervention. Although many NMDs were previously incurable, recent breakthroughs in the
      molecular pathogenesis of monogenic and acquired disorders are now revealing potential
      targeted disease-modifying therapies that may improve muscle health and prevent disability.
      The goal is to assess clinical samples such as blood, skin/muscle biopsies, cerebrospinal
      fluid obtained through collaboration with NMC clinicians and researchers to help develop
      effective novel/known drug compounds that may act as promising therapies that, in the future,
      can be rapidly moved into local and multicenter clinical trials.
observational model: Other
time perspective: Other
measure: To provide a more rapid diagnosis for patients with rare NMD and identify NMD biomarkers.
time frame: 5 years
description: Identification of genes responsible for rare genetic NMD diseases, biomarkers, and imaging techniques to aid in diagnosis and disease management.
Genetic and Biomarker Samples: 5 to 10 ml of blood or saliva will be collected preferably during routine medical care for DNA extraction. Urine or other bodily fluid collection will be used for biomarker studies. Fibroblast or myoblast samples can be used to establish a cell line. Unaffected family members can also provide tissue samples for DNA extraction or establishment of cell lines that will be stored in the Ottawa Hospital Neuromuscular Biobank.
Imaging: Routine diagnostic imaging studies will be analyzed for pattern of involvement: Electrodiagnostic Studies (Nerve Conduction and Electromyogram Studies) will be included to assess nerve and muscle dysfunction, Ultrasound images of affected muscles and nerves, and MRI whole-body scans will be obtained for whole muscle qualitative evaluation and to assess inflammation and edema
measure: To characterize disease mechanisms to advance potential therapies of tomorrow.
time frame: 5 years
description: Disease Characterization: Functional validation of gene candidates
Genetic Diagnosis: Disease-causing genetic variants must be proven with genetic or functional data. Biochemical validation of a putative pathological variant to confirm the functional significance of a newly identified mutation can be considered confirmatory in some cases.
Biomarker Development: We will use patient-derived material to develop biomarkers using metabolomic, proteomic, and transcriptional profiling. We will perform computational and in vitro screens using system-wide RNA and chemical libraries to look for modifications of disease-specific biomarkers.
Sample analysis: We developed a collaborative network of laboratory-based scientists at the Ottawa Hospital Research Institute, University of Ottawa Faculty of Medicine, and the Children's Hospital of Eastern Ontario, and across Canada. This is vital to the validation of gene candidates and biomechanical mechanisms for the diagnosis or rare dis
intervention type: Other
intervention name: B3 for NMD: Bench to Bedside and Back
description: Transformative discoveries leading to improved care in Neuromuscular Disease
Whole Blood, CSF, Saliva, Skin Biopsy, and Muscle Biospy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Dr. Jodi Warman Chardon, MD MSc FRCPC
role: Principal Investigator
affiliation: Ottawa Hospital Research Institute
last name: Maria Liezl Vinci Duff
phone: 613-798-5555
phone ext: 19070
email: maduff@ohri.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Neuromuscular Diseases
sharing ipd: No