<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/NCT03300726</url>
  </required_header>
  <id_info>
    <org_study_id>2017H0255</org_study_id>
    <nct_id>NCT03300726</nct_id>
  </id_info>
  <brief_title>Synaptic Injury and Functional Connectivity in Alzheimer's Disease</brief_title>
  <official_title>Cerebrospinal Fluid Markers of Synaptic Injury and Functional Connectivity in Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ohio State University</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 examine cross-sectional associations between CSF markers of&#xD;
      synaptic injury (Ng and SNAP-25) and functional connectivity in default and semantic memory&#xD;
      networks using 3T- fMRI in individuals with MCI (i.e. the earliest clinically detectable&#xD;
      stage of cognitive impairment) due to AD or mild AD dementia (CDR 0.5-1; n=20) and&#xD;
      cognitively normal controls (CDR 0; n=20).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      SPECIFIC AIMS:&#xD;
&#xD;
      Aim 1: Investigate correlations between CSF biomarkers of synaptic injury (Ng and SNAP-25)&#xD;
      and functional connectivity (FC) within the default mode network (DMN) using resting-state&#xD;
      fMRI (adjusting for age, gender, apolipoprotein-E4 [APOE4] genotype, task performance, and&#xD;
      regional brain atrophy) in MCI/AD and controls.&#xD;
&#xD;
      Aim 2: Examine correlations between CSF biomarkers of synaptic injury and functional&#xD;
      connectivity (FC) within the semantic memory network on task-activated fMRI using the Famous&#xD;
      Name Discrimination Task (FNDT) (adjusting for age, gender, APOE4 genotype, task performance,&#xD;
      and regional brain atrophy) in MCI/AD and controls.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 12, 2018</start_date>
  <completion_date type="Actual">September 22, 2021</completion_date>
  <primary_completion_date type="Actual">September 22, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlations between CSF biomarker measurements and fMRI measures of functional connectivity at baseline</measure>
    <time_frame>Study duration is 3 years (36 months) for each participant, including 3 visits: one for cognitive evaluations, one for fMRI, and one for CSF collection.</time_frame>
    <description>Cross-sectional associations between CSF biomarker measurements and fMRI measures at baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CSF levels of tau, p-tau181, Abeta42, Ng, and SNAP-25 (pg/ml)</measure>
    <time_frame>CSF collection will be performed for each participant once during the study (within 3 years of study enrollment).</time_frame>
    <description>Quantification of biomarker levels in CSF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Connectivity measures on functional MRI (r)</measure>
    <time_frame>fMRI will be performed for each participant once during the study (within 3 years of study enrollment).</time_frame>
    <description>Functional Connectivity Measures on fMRI during resting state and task activation</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">35</enrollment>
  <condition>Alzheimer Disease, Late Onset</condition>
  <arm_group>
    <arm_group_label>MCI due to AD or mild AD dementia</arm_group_label>
    <description>The clinical diagnoses of amnestic MCI due to AD or mild AD dementia will be made according to standard clinical criteria as described by the National Institute of Aging -Alzheimer's Association Working Group and supported by CSF biomarker data for tau, p-tau181, and Aβ42. This includes evaluation for other systemic or neurological disorders which could account for the cognitive impairment, and inclusion of results from ancillary structural imaging (CT or structural MRI), neuro-psychometric testing, and FDG-PET imaging (when available) into the diagnostic scheme. All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal controls</arm_group_label>
    <description>Normal cognition will be defined as cognitive performance on detailed neuropsychometric testing that falls within 1 SD of age-, gender-, and education-matched norms in all cognitive domains, and no subjective report of cognitive decline from an individual's baseline (i.e. CDR 0). All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>CSF analysis</intervention_name>
    <description>CSF analysis for tau, p-tau181, Abeta42, and CSF levels of markers of synaptic injury</description>
    <arm_group_label>MCI due to AD or mild AD dementia</arm_group_label>
    <arm_group_label>Normal controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Functional MRI</intervention_name>
    <description>Functional MRI during resting state and semantic memory task activation</description>
    <arm_group_label>MCI due to AD or mild AD dementia</arm_group_label>
    <arm_group_label>Normal controls</arm_group_label>
  </intervention>
  <biospec_retention>None Retained</biospec_retention>
  <biospec_descr>
    <textblock>
      Cerebrospinal fluid (CSF) and plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants will be recruited from the community and the Memory Disorders Clinic of The&#xD;
        OSU Wexner Medical Center Department of Neurology. This study will include cognitively&#xD;
        normal individuals (CDR 0; n=20), individuals with a clinical diagnosis of single-domain or&#xD;
        multi-domain amnestic MCI due to AD or mild AD dementia (CDR 0.5 or 1; n=20).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria: Participants included in the study should meet all 4 inclusion&#xD;
        criteria:&#xD;
&#xD;
          1. 60 years of age or older&#xD;
&#xD;
          2. A clinical diagnosis of MCI, mild AD dementia, or normal cognition&#xD;
&#xD;
          3. No significant medical or surgical co-morbidities&#xD;
&#xD;
          4. No contraindications to LP or MRI.&#xD;
&#xD;
        Exclusion criteria: Participants with any of the following criteria will be excluded from&#xD;
        the study:&#xD;
&#xD;
          1. Participants with MCI due to AD or mild AD dementia who have been treated with&#xD;
             cholinesterase inhibitors or glutamate antagonists in the 3 months prior to study&#xD;
             enrollment&#xD;
&#xD;
          2. Individuals with any past history of ischemic or traumatic brain injury&#xD;
&#xD;
          3. Individuals with imaging evidence of significant cerebrovascular disease or structural&#xD;
             brain lesions (e.g. tumor, demyelinating disorders, infection, or congenital&#xD;
             anomalies)&#xD;
&#xD;
          4. Active mood disorder&#xD;
&#xD;
          5. Active alcohol use&#xD;
&#xD;
          6. Active use of benzodiazepines, barbiturates, anticholinergic, or anti-epileptic&#xD;
             medications&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rawan Tarawneh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ohio State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>September 25, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>September 22, 2021</last_update_submitted>
  <last_update_submitted_qc>September 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ohio State University</investigator_affiliation>
    <investigator_full_name>Rawan Tarawneh</investigator_full_name>
    <investigator_title>Assistant Professor of Neurology</investigator_title>
  </responsible_party>
  <keyword>Synaptic injury</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Late Onset Disorders</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/NCT03300726
org study id: 2017H0255
nct id: NCT03300726
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to examine cross-sectional associations between CSF markers of
      synaptic injury (Ng and SNAP-25) and functional connectivity in default and semantic memory
      networks using 3T- fMRI in individuals with MCI (i.e. the earliest clinically detectable
      stage of cognitive impairment) due to AD or mild AD dementia (CDR 0.5-1; n=20) and
      cognitively normal controls (CDR 0; n=20).
SPECIFIC AIMS:

      Aim 1: Investigate correlations between CSF biomarkers of synaptic injury (Ng and SNAP-25)
      and functional connectivity (FC) within the default mode network (DMN) using resting-state
      fMRI (adjusting for age, gender, apolipoprotein-E4 [APOE4] genotype, task performance, and
      regional brain atrophy) in MCI/AD and controls.

      Aim 2: Examine correlations between CSF biomarkers of synaptic injury and functional
      connectivity (FC) within the semantic memory network on task-activated fMRI using the Famous
      Name Discrimination Task (FNDT) (adjusting for age, gender, APOE4 genotype, task performance,
      and regional brain atrophy) in MCI/AD and controls.
observational model: Case-Control
time perspective: Prospective
measure: Correlations between CSF biomarker measurements and fMRI measures of functional connectivity at baseline
time frame: Study duration is 3 years (36 months) for each participant, including 3 visits: one for cognitive evaluations, one for fMRI, and one for CSF collection.
description: Cross-sectional associations between CSF biomarker measurements and fMRI measures at baseline
measure: CSF levels of tau, p-tau181, Abeta42, Ng, and SNAP-25 (pg/ml)
time frame: CSF collection will be performed for each participant once during the study (within 3 years of study enrollment).
description: Quantification of biomarker levels in CSF
measure: Functional Connectivity measures on functional MRI (r)
time frame: fMRI will be performed for each participant once during the study (within 3 years of study enrollment).
description: Functional Connectivity Measures on fMRI during resting state and task activation
arm group label: MCI due to AD or mild AD dementia
description: The clinical diagnoses of amnestic MCI due to AD or mild AD dementia will be made according to standard clinical criteria as described by the National Institute of Aging -Alzheimer's Association Working Group and supported by CSF biomarker data for tau, p-tau181, and Aβ42. This includes evaluation for other systemic or neurological disorders which could account for the cognitive impairment, and inclusion of results from ancillary structural imaging (CT or structural MRI), neuro-psychometric testing, and FDG-PET imaging (when available) into the diagnostic scheme. All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks.
arm group label: Normal controls
description: Normal cognition will be defined as cognitive performance on detailed neuropsychometric testing that falls within 1 SD of age-, gender-, and education-matched norms in all cognitive domains, and no subjective report of cognitive decline from an individual's baseline (i.e. CDR 0). All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks.
intervention type: Diagnostic Test
intervention name: CSF analysis
description: CSF analysis for tau, p-tau181, Abeta42, and CSF levels of markers of synaptic injury
arm group label: MCI due to AD or mild AD dementia
arm group label: Normal controls
intervention type: Radiation
intervention name: Functional MRI
description: Functional MRI during resting state and semantic memory task activation
arm group label: MCI due to AD or mild AD dementia
arm group label: Normal controls
Cerebrospinal fluid (CSF) and plasma
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 60 Years
maximum age: 95 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Rawan Tarawneh, MD
role: Principal Investigator
affiliation: Ohio State University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Ohio State University
investigator full name: Rawan Tarawneh
investigator title: Assistant Professor of Neurology
mesh term: Alzheimer Disease
mesh term: Late Onset Disorders
sharing ipd: No