<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/NCT02263235</url>
  </required_header>
  <id_info>
    <org_study_id>8652</org_study_id>
    <nct_id>NCT02263235</nct_id>
  </id_info>
  <brief_title>In Vivo Alzheimer Proteomics</brief_title>
  <acronym>PROMARA</acronym>
  <official_title>Use of Targeted Quantitative Proteomics and Metabolic Labelling With Stable Isotopes for the Diagnosis and the Investigation of Neurological Disorders and in Particular Alzheimer Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Clermont-Ferrand</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>International Atomic Energy Agency</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Montpellier</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In France, an estimated 860 000 patients are affected by Alzheimer Disease (AD) which&#xD;
      represents, as in other developed countries, a major public health issue. In many cases, AD&#xD;
      diagnosis is uncertain and its clinical evolution unpredictable. The exactitude of the&#xD;
      diagnosis is however particularly important in the perspective of the validation and use of&#xD;
      new therapeutic strategies in AD. Detection of cerebrospinal fluid (CSF) diagnosis biomarkers&#xD;
      fell short in the detection, of atypical/mixed cases, of some differential diagnosis, and in&#xD;
      differentiating rapid or slow clinical evolutions. Hence, CSF analysis gives a unique&#xD;
      opportunity to detect and validate biomarkers in many neurological disorders. Nevertheless,&#xD;
      in medical practice, CSF biological analysis is currently limited to a small number of&#xD;
      analytes.Quantitative and targeted mass spectrometry, especially operated in the Multiple&#xD;
      reaction monitoring mode (MRM), represents an alternative to immunodetection and could be&#xD;
      used to detect specific biomarkers in complex matrices such as plasma by specifically&#xD;
      discriminating the proteotypic peptides corresponding to each proteins. Mass spectrometry has&#xD;
      also the ability to distinguish and quantify isotopically labelled and unlabeled selected&#xD;
      targets. This ability was used in a publication by the group of R. Bateman (Washington&#xD;
      University, St Louis, USA) who could, after administering stable isotope-labelled leucine,&#xD;
      evaluate Ab synthesis and clearance in humans. This approach has an enormous potential to&#xD;
      study the metabolism of proteins within the human CNS and consequently help in the&#xD;
      understanding and diagnosis of neurological disorders.The main objective of this program is&#xD;
      set up a targeted quantitative mass spectrometry method for existing and stable&#xD;
      isotope-labelled CSF biomarkers in the neurological field; exploit this approach for&#xD;
      diagnostic purpurses and to gain knowledge in the pathophysiology of diseases.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    end of the inclusion period&#xD;
  </why_stopped>
  <start_date type="Actual">October 8, 2013</start_date>
  <completion_date type="Actual">May 22, 2018</completion_date>
  <primary_completion_date type="Actual">May 22, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>C13 Leucine incorporation in Amyloid peptides (1-40, 1-42) at different time points (in %)</measure>
    <time_frame>1.5 years</time_frame>
    <description>Analysis of labelled samples with mass spectrometry. Data generated will be studied to validate the experimental model and understand the pathophysiology of neurological disorders. A collection of labelled biological samples will also be generated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %)</measure>
    <time_frame>1.5 years</time_frame>
    <description>C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %)</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">89</enrollment>
  <condition>Probable Alzheimer Disease</condition>
  <condition>Parkinson Disease</condition>
  <condition>Neurological Disease Without Cognitive Degradation</condition>
  <condition>Brain Trauma</condition>
  <condition>Acute Hydrocephaly</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 patients (20 probable AD, 20 Parkinson Disease (PK), 20 neurological disease without cognitive degradation)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 patients (patients with brain trauma, acute hydrocephaly), with temporary derivation of the CSF</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 patients (15 probable AD, 15 neurological disease without cognitive degradation)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>administration of stable isotope-labelled leucine-</intervention_name>
    <description>- administration of stable isotope-labelled leucine : by drip, for group 2A and group 2B. Group 1 (control group) : 1 collection of CSF. Group 2B : 4 collections of CSF, 24 hours after administration of stable isotope-labelled leucin. Group 2A (patients with brain trauma, acute hydrocephaly) : continuous collection of CSF, for 24 to 36 hours</description>
    <arm_group_label>Group 2A</arm_group_label>
    <arm_group_label>Group 2B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>collection of CSF, blood, urine, saliva</intervention_name>
    <description>- administration of stable isotope-labelled leucine : by drip, for group 2A and group 2B. Group 1 (control group) : 1 collection of CSF. Group 2B : 4 collections of CSF, 24 hours after administration of stable isotope-labelled leucin. Group 2A (patients with brain trauma, acute hydrocephaly) : continuous collection of CSF, for 24 to 36 hours</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Reports written consent, informed and signed by the patient and a trusted person&#xD;
&#xD;
          -  Subject member or beneficiary of a social security system&#xD;
&#xD;
        Specific criteria for group 1 and 2B :&#xD;
&#xD;
          -  Age between 55 and 85 years old for patients&#xD;
&#xD;
          -  Subject with AD or other neurodegenerative disease (frontotemporal dementia, dementia&#xD;
             with Lewy bodies, Parkinson disease)&#xD;
&#xD;
          -  Subjects with chronic adult hydrocephalus (HCA) requiring depletion lumbar puncture&#xD;
             (PL)&#xD;
&#xD;
        Specific criteria for group 2A :&#xD;
&#xD;
        - Adult patient requiring neurosurgery with CSF shunt (subject with brain trauma, acute&#xD;
        hydrocephaly) and favorable evolution that allows removal of the shunt&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient deprived of liberty by judicial or administrative decision&#xD;
&#xD;
          -  Major protected by law&#xD;
&#xD;
          -  Pregnancy, women of childbearing age with risk of pregnancy, or breast-feeding&#xD;
&#xD;
          -  Presence of a transmissible viral disease (HlV, hepatitis B and C)&#xD;
&#xD;
          -  Patient included in a clinical trial&#xD;
&#xD;
          -  lnadequate cardiac, hepatic or severe renal disfunction&#xD;
&#xD;
          -  Disease amino acid metabolism (Leucinose..)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Information clinical and para-clinical insufficient or unavailable&#xD;
&#xD;
          -  Patient deprived of liberty by judicial or administrative decision&#xD;
&#xD;
          -  Major protected by law&#xD;
&#xD;
          -  Pregnancy, women of childbearing age with risk of pregnancy, or breast&#xD;
&#xD;
          -  feeding&#xD;
&#xD;
          -  Presence of a transmissible viral disease (HIV, hepatitis B and C)&#xD;
&#xD;
          -  Patient included in a clinical trial&#xD;
&#xD;
          -  Patient exclusion period relative to another protocol or for which the maximum annual&#xD;
             compensation of 4500€ has been reached&#xD;
&#xD;
          -  Inadequate cardiac, hepatic or severe renal&#xD;
&#xD;
          -  Disease amino acid metabolism (Leucinose..)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sylvain Lehmann, PU-PH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laboratoire de Biochimie et Protéomique Clinique, IRMB St Eloi, CHRU de Montpellier</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Laboratoire de Biochimie et Protéomique Clinique, CHU Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>December 27, 2021</last_update_submitted>
  <last_update_submitted_qc>December 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alzheimer disease (AD)</keyword>
  <keyword>diagnosis biomarkers</keyword>
  <keyword>cerebrospinal fluid (CSF)</keyword>
  <keyword>targeted quantitative proteomics</keyword>
  <keyword>mass spectrometry</keyword>
  <keyword>stable isotope-labelled leucine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Nervous System Diseases</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Hydrocephalus</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/NCT02263235
org study id: 8652
nct id: NCT02263235
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
In France, an estimated 860 000 patients are affected by Alzheimer Disease (AD) which
      represents, as in other developed countries, a major public health issue. In many cases, AD
      diagnosis is uncertain and its clinical evolution unpredictable. The exactitude of the
      diagnosis is however particularly important in the perspective of the validation and use of
      new therapeutic strategies in AD. Detection of cerebrospinal fluid (CSF) diagnosis biomarkers
      fell short in the detection, of atypical/mixed cases, of some differential diagnosis, and in
      differentiating rapid or slow clinical evolutions. Hence, CSF analysis gives a unique
      opportunity to detect and validate biomarkers in many neurological disorders. Nevertheless,
      in medical practice, CSF biological analysis is currently limited to a small number of
      analytes.Quantitative and targeted mass spectrometry, especially operated in the Multiple
      reaction monitoring mode (MRM), represents an alternative to immunodetection and could be
      used to detect specific biomarkers in complex matrices such as plasma by specifically
      discriminating the proteotypic peptides corresponding to each proteins. Mass spectrometry has
      also the ability to distinguish and quantify isotopically labelled and unlabeled selected
      targets. This ability was used in a publication by the group of R. Bateman (Washington
      University, St Louis, USA) who could, after administering stable isotope-labelled leucine,
      evaluate Ab synthesis and clearance in humans. This approach has an enormous potential to
      study the metabolism of proteins within the human CNS and consequently help in the
      understanding and diagnosis of neurological disorders.The main objective of this program is
      set up a targeted quantitative mass spectrometry method for existing and stable
      isotope-labelled CSF biomarkers in the neurological field; exploit this approach for
      diagnostic purpurses and to gain knowledge in the pathophysiology of diseases.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: C13 Leucine incorporation in Amyloid peptides (1-40, 1-42) at different time points (in %)
time frame: 1.5 years
description: Analysis of labelled samples with mass spectrometry. Data generated will be studied to validate the experimental model and understand the pathophysiology of neurological disorders. A collection of labelled biological samples will also be generated.
measure: C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %)
time frame: 1.5 years
description: C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %)
arm group label: Group 1
arm group type: Experimental
description: 60 patients (20 probable AD, 20 Parkinson Disease (PK), 20 neurological disease without cognitive degradation)
arm group label: Group 2A
arm group type: Experimental
description: 20 patients (patients with brain trauma, acute hydrocephaly), with temporary derivation of the CSF
arm group label: Group 2B
arm group type: Experimental
description: 30 patients (15 probable AD, 15 neurological disease without cognitive degradation)
intervention type: Biological
intervention name: administration of stable isotope-labelled leucine-
description: - administration of stable isotope-labelled leucine : by drip, for group 2A and group 2B. Group 1 (control group) : 1 collection of CSF. Group 2B : 4 collections of CSF, 24 hours after administration of stable isotope-labelled leucin. Group 2A (patients with brain trauma, acute hydrocephaly) : continuous collection of CSF, for 24 to 36 hours
arm group label: Group 2A
arm group label: Group 2B
intervention type: Other
intervention name: collection of CSF, blood, urine, saliva
description: - administration of stable isotope-labelled leucine : by drip, for group 2A and group 2B. Group 1 (control group) : 1 collection of CSF. Group 2B : 4 collections of CSF, 24 hours after administration of stable isotope-labelled leucin. Group 2A (patients with brain trauma, acute hydrocephaly) : continuous collection of CSF, for 24 to 36 hours
arm group label: Group 1
criteria: 
gender: All
minimum age: 55 Years
maximum age: 85 Years
healthy volunteers: No
last name: Sylvain Lehmann, PU-PH
role: Principal Investigator
affiliation: Laboratoire de Biochimie et Protéomique Clinique, IRMB St Eloi, CHRU de Montpellier
facility: 
country: France
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Alzheimer Disease
mesh term: Nervous System Diseases
mesh term: Brain Injuries, Traumatic
mesh term: Hydrocephalus