<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/NCT04450992</url>
  </required_header>
  <id_info>
    <org_study_id>S19-01846</org_study_id>
    <nct_id>NCT04450992</nct_id>
  </id_info>
  <brief_title>TRACK-MSA: A Longitudinal Study to Define Outcome Measures in Multiple System Atrophy</brief_title>
  <official_title>TRACK-MSA: An Observational Longitudinal Oligo-Center Study to Define Clinical, Biofluid, Imaging and Digital Outcome Measures in Multiple System Atrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU Langone Health</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>
      TRACK-MSA is an observational, non-interventional, longitudinal natural history study to&#xD;
      define changes in clinical, neurological, blood, CSF, and neuroimaging biomarkers in patients&#xD;
      with multiple system atrophy (MSA) comparing baseline to 6-month and 1-year assessments. The&#xD;
      study will enroll 50 patients with MSA-P or MSA-C at 2 or more participating sites.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TRACK-MSA is designed to relate phenotypic characteristics of participants with MSA using&#xD;
      several modalities (i.e., clinical, quantitative motor, imaging, laboratory) in order to&#xD;
      relate phenotypic characteristics with data derived from the study of blood and CSF (&quot;wet&#xD;
      biomarkers&quot;) and imaging or wearables (&quot;dry biomarkers&quot;).&#xD;
&#xD;
      It is possible that the cohort enrolled in this study will, after study completion, be&#xD;
      recruited into the earliest multicenter biomarker-driven clinical trials of disease modifying&#xD;
      agents for MSA. As such, the data collected in the TRACK-MSA study could constitute a&#xD;
      valuable observational non-interventional arm of potential disease-modifying treatments.&#xD;
&#xD;
      The objective of the study will therefore be to determine the combination of measures that&#xD;
      most sensitively detects changes over the natural course of MSA, with a goal of validating&#xD;
      these measures for use in future clinical trials.&#xD;
&#xD;
      TRACK-MSA will be a 1-year observational, longitudinal, non-interventional natural history&#xD;
      study of patients with MSA. The study will be carried out at least at 2 sites (NYU being the&#xD;
      primary site). All participants will be assessed at baseline, 6-month and 1-year visits.&#xD;
      Participants will undergo clinical, neurological, quantitative motor, MRI assessments, in&#xD;
      addition to donating blood and CSF samples at some or all of the visits.&#xD;
&#xD;
      For a given participant, the same investigator should carry out the clinical assessment&#xD;
      throughout the study where possible.&#xD;
&#xD;
      It is anticipated that the study will complete enrollment in 2 years since startup, and&#xD;
      complete all the follow-up evaluations within 3 years from startup.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 17, 2020</start_date>
  <completion_date type="Anticipated">July 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2024</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>Brain MRI imaging data</measure>
    <time_frame>5 years</time_frame>
    <description>Diffusion-based MRI data</description>
  </primary_outcome>
  <primary_outcome>
    <measure>neurofilament light chain (NfL) in serum and/or plasma</measure>
    <time_frame>5 years</time_frame>
    <description>Blood samples for measure measurement of NfL</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cerebral spinal fluid (CSF) measures</measure>
    <time_frame>5 years</time_frame>
    <description>measurement of alpha synuclein, aggregated alpha synuclein Tau/phosphorylated Tau, neurofilament light chain, neurofilament heavy chain, and catecholamines in CSF</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantitative movement assessment</measure>
    <time_frame>5 years</time_frame>
    <description>The quantitative movement assessment comprises a battery of tests performed with non-invasive motion sensors, to capture disease features associated with striatonigral degeneration; others are aimed at capturing features associated with olivopontocerebellar degeneration observed in MSA patients.</description>
  </primary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Multiple System Atrophy</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Biomarker analysis will be focused on measuring the levels of neurofilament light chain (NfL)&#xD;
      in serum and/or plasma, which is one of the most promising blood biomarkers in MSA.&#xD;
&#xD;
      Analysis of CSF may include but is not limited to the following biomarkers: total alpha&#xD;
      synuclein, aggregated alpha synuclein Tau/phosphorylated Tau, neurofilament light chain,&#xD;
      neurofilament heavy chain, and catecholamines (dopamine, norepinephrine, DOPAC, DHPG).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Multiple system atrophy&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - 1. Ability to understand the purpose and risks of the study and provide signed and dated&#xD;
        informed consent and authorization to use confidential health information in accordance&#xD;
        with applicable privacy regulations 2. Diagnosis of probable or possible multiple system&#xD;
        atrophy (MSA-P or MSA-C) according to current consensus diagnostic criteria [8].&#xD;
&#xD;
        3. Aged 40-80 with anticipated survival of at least 3 years (in the opinion of the&#xD;
        Investigator) 4. Able to walk for, at least, 10 meters with or without assistance 5.&#xD;
        Willingness and ability to participate in all study procedures. 6. Ability to tolerate and&#xD;
        no contraindications for brain MRI. 7. Ability to tolerate and no contraindications for CSF&#xD;
        collection. Participants with contraindication to the CSF procedure will be given the&#xD;
        option to participate in the study and opt out the CSF collection. An effort will be made&#xD;
        to ensure that at least 50% of patients enrolled in the study undergo CSF collection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Presence of supranuclear gaze palsy. 2. Known presence of hyposmia (i.e., reduced&#xD;
             ability to smell and detect odors).&#xD;
&#xD;
             3. Presence of cognitive dysfunction (defined as MoCA score &lt;20). 4.&#xD;
             Severe-to-complete dependence on caregivers (score &gt;3 on UMSARS Part IV, Global&#xD;
             Disability), severe impairment of swallowing (score ≥3 on UMSARS Part I, Question 2),&#xD;
             or frequent falls (score ≥3 on UMSARS Part I, Question 8) at Baseline.&#xD;
&#xD;
             5. Family history or a known genetic cause of ataxia or parkinsonism. 6. Clinically&#xD;
             significant neuropathy. 7. Hallucinations not induced by drugs. 8. Unstable&#xD;
             psychiatric illness, including psychosis, suicidal ideation, or untreated major&#xD;
             depression within 90 days before Baseline, as determined by the Investigator.&#xD;
&#xD;
             9. History or Baseline MRI results showing evidence of structural abnormalities that&#xD;
             could contribute to the participant's clinical state other than findings typical of&#xD;
             MSA, or any finding that might pose a risk to the participant.&#xD;
&#xD;
             10. Any contraindications to having a brain MRI (e.g., pacemaker; MRI-incompatible&#xD;
             aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia&#xD;
             that cannot be medically managed without requiring general anesthesia, etc.).&#xD;
&#xD;
             11. Transient ischemic attack or stroke, or any unexplained loss of consciousness&#xD;
             within 1 year before Baseline.&#xD;
&#xD;
             12. History of any brain surgery for MSA (e.g., pallidotomy, deep brain stimulation,&#xD;
             or fetal tissue transplant) or a history of focused ultrasound treatment or&#xD;
             neuromodulation procedures, including but not limited to transcranial magnetic&#xD;
             stimulation (TMS) and transcranial direct or alternating current stimulation&#xD;
             (tDCS/tACS) that have been performed within 90 days of Baseline.&#xD;
&#xD;
        Infection Risk 13. History of human immunodeficiency virus or hepatitis C virus antibody.&#xD;
        14. Chronic, recurrent, or serious infection (e.g., pneumonia, septicemia, recurrent&#xD;
        urinary tract infection), as determined by the Investigator, within 8 weeks before Day 1.&#xD;
&#xD;
        Cardiovascular 15. History of unstable angina, myocardial infarction, chronic heart failure&#xD;
        (New York Heart Association Class 3 or 4), or clinically significant conduction&#xD;
        abnormalities (e.g., unstable atrial fibrillation) within 1 year before Baseline.&#xD;
&#xD;
        16. Chronic, sustained, uncontrolled supine hypertension (unrelated to pharmacological&#xD;
        treatment of orthostatic hypotension) defined by an average of three SBP readings of &gt;180&#xD;
        mmHg or DBP readings of &gt;110 mmHg at baseline.&#xD;
&#xD;
        17. In participants treated pharmacologically for orthostatic hypotension, any documented&#xD;
        sitting or standing SBP reading ≥180 mmHg or DBP reading ≥110 mmHg within the 3 months&#xD;
        before Day 1 or on Day 1).&#xD;
&#xD;
        18. Severe orthostatic hypotension despite optimal medical management (defined as a score&#xD;
        of ≥3 on UMSARS Part I, Question 9).&#xD;
&#xD;
        Oncology 19. History of, or ongoing, malignant disease, including solid tumors and&#xD;
        hematologic malignancies (with the exception of basal cell carcinomas and squamous cell&#xD;
        carcinomas that have been completely excised and considered cured at least 12 months prior&#xD;
        to Day -1). Participants with cancers in remission for greater than 5 years prior to Day -1&#xD;
        may be included.&#xD;
&#xD;
        Metabolic 20. Poorly controlled diabetes mellitus, as defined by having dosage adjustment&#xD;
        of diabetic medication within 3 months before dosing (Day 1) or glycated hemoglobin value&#xD;
        ≥8% at Baseline.&#xD;
&#xD;
        Hypersensitivity 21. Clinically significant allergies, as determined by the Investigator,&#xD;
        to anesthetics that will be used for the LP per institutional practice, or iodine.&#xD;
&#xD;
        Other Medical History or Health Status 22. History of any clinically significant&#xD;
        endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary,&#xD;
        neurologic, dermatologic, renal ischemic, or other major diseases, as determined by the&#xD;
        Investigator.&#xD;
&#xD;
        23. Surgery within 12 weeks before Day 1 (other than minor cosmetic surgery and minor&#xD;
        dental surgery, as determined by the Investigator).&#xD;
&#xD;
        Any contraindications to LP procedures, including but not limited to:&#xD;
&#xD;
        24. Known or suspected structural abnormality of the lumbar spine, including but not&#xD;
        limited to X-ray, MRI, or myelographic evidence of significant lumbar spine abnormalities,&#xD;
        or other anatomical factors at or near the LP site that, in the opinion of the&#xD;
        Investigator, may interfere with the performance of the LP, render repeated LPs difficult,&#xD;
        or increase the risk of the procedure for the participant.&#xD;
&#xD;
        25. Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is&#xD;
        not managed optimally and might place a participant at an increased risk for intraoperative&#xD;
        or postoperative bleeding. These could include, but are not limited to, anatomical factors&#xD;
        at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities),&#xD;
        known underlying disorders of the coagulation cascade, platelet function, or platelet count&#xD;
        (e.g., hemophilia, von Willebrand's disease, liver disease).&#xD;
&#xD;
        26. Unwillingness or inability to comply with the requirements of this protocol.&#xD;
&#xD;
        27. Other unspecified reasons that, in the opinion of the Investigator, make the&#xD;
        participant unsuitable for enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Jose-Alberto Palma, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jose Martinez, MA</last_name>
    <phone>212 263 2775</phone>
    <email>jose.martinez4@nyulangone.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lee-Ann Lugg</last_name>
    <phone>212 263 7225</phone>
    <email>Lee-Ann.Lugg@nyulangone.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>NYU Langone Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jose Martinez, MA</last_name>
      <phone>212-263-7225</phone>
      <email>jose.martinez4@nyulangone.org</email>
    </contact>
    <contact_backup>
      <last_name>Lee-Ann Lugg</last_name>
      <phone>212 263 7225</phone>
      <email>Lee-Ann.Lugg@nyulangone.org</email>
    </contact_backup>
    <investigator>
      <last_name>Jose-Alberto Palma, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>May 10, 2023</last_update_submitted>
  <last_update_submitted_qc>May 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2023</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>Multiple System Atrophy</mesh_term>
    <mesh_term>Shy-Drager Syndrome</mesh_term>
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Only de-identified, coded data will be shared with other researchers</ipd_description>
  </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/NCT04450992
org study id: S19-01846
nct id: NCT04450992
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
TRACK-MSA is an observational, non-interventional, longitudinal natural history study to
      define changes in clinical, neurological, blood, CSF, and neuroimaging biomarkers in patients
      with multiple system atrophy (MSA) comparing baseline to 6-month and 1-year assessments. The
      study will enroll 50 patients with MSA-P or MSA-C at 2 or more participating sites.
TRACK-MSA is designed to relate phenotypic characteristics of participants with MSA using
      several modalities (i.e., clinical, quantitative motor, imaging, laboratory) in order to
      relate phenotypic characteristics with data derived from the study of blood and CSF ("wet
      biomarkers") and imaging or wearables ("dry biomarkers").

      It is possible that the cohort enrolled in this study will, after study completion, be
      recruited into the earliest multicenter biomarker-driven clinical trials of disease modifying
      agents for MSA. As such, the data collected in the TRACK-MSA study could constitute a
      valuable observational non-interventional arm of potential disease-modifying treatments.

      The objective of the study will therefore be to determine the combination of measures that
      most sensitively detects changes over the natural course of MSA, with a goal of validating
      these measures for use in future clinical trials.

      TRACK-MSA will be a 1-year observational, longitudinal, non-interventional natural history
      study of patients with MSA. The study will be carried out at least at 2 sites (NYU being the
      primary site). All participants will be assessed at baseline, 6-month and 1-year visits.
      Participants will undergo clinical, neurological, quantitative motor, MRI assessments, in
      addition to donating blood and CSF samples at some or all of the visits.

      For a given participant, the same investigator should carry out the clinical assessment
      throughout the study where possible.

      It is anticipated that the study will complete enrollment in 2 years since startup, and
      complete all the follow-up evaluations within 3 years from startup.
observational model: Cohort
time perspective: Prospective
measure: Brain MRI imaging data
time frame: 5 years
description: Diffusion-based MRI data
measure: neurofilament light chain (NfL) in serum and/or plasma
time frame: 5 years
description: Blood samples for measure measurement of NfL
measure: Cerebral spinal fluid (CSF) measures
time frame: 5 years
description: measurement of alpha synuclein, aggregated alpha synuclein Tau/phosphorylated Tau, neurofilament light chain, neurofilament heavy chain, and catecholamines in CSF
measure: Quantitative movement assessment
time frame: 5 years
description: The quantitative movement assessment comprises a battery of tests performed with non-invasive motion sensors, to capture disease features associated with striatonigral degeneration; others are aimed at capturing features associated with olivopontocerebellar degeneration observed in MSA patients.
Biomarker analysis will be focused on measuring the levels of neurofilament light chain (NfL)
      in serum and/or plasma, which is one of the most promising blood biomarkers in MSA.

      Analysis of CSF may include but is not limited to the following biomarkers: total alpha
      synuclein, aggregated alpha synuclein Tau/phosphorylated Tau, neurofilament light chain,
      neurofilament heavy chain, and catecholamines (dopamine, norepinephrine, DOPAC, DHPG).
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
last name: Jose-Alberto Palma, MD PhD
role: Principal Investigator
affiliation: NYU School of Medicine
last name: Jose Martinez, MA
phone: 212 263 2775
email: jose.martinez4@nyulangone.org
last name: Lee-Ann Lugg
phone: 212 263 7225
email: Lee-Ann.Lugg@nyulangone.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Multiple System Atrophy
mesh term: Shy-Drager Syndrome
mesh term: Atrophy
sharing ipd: No
ipd description: Only de-identified, coded data will be shared with other researchers