<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/NCT01705210</url>
  </required_header>
  <id_info>
    <org_study_id>NL34329.068.10 / METC 10-2-023</org_study_id>
    <secondary_id>916.11.059</secondary_id>
    <nct_id>NCT01705210</nct_id>
  </id_info>
  <brief_title>Functional MRI Biomarkers of Cognitive Decrements in Diabetes</brief_title>
  <official_title>Functional MRI Biomarkers of Cognitive Decrements in Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ZonMw: The Netherlands Organisation for Health Research and Development</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Netherlands Organisation for Scientific Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The exact neuronal mechanism underlying the cognitive decline associated with diabetes&#xD;
      mellitus type 2 (DM2) still remains to be elucidated. Multi-parametric functional MRI can&#xD;
      potentially provide functional, micro-structural, micro-vascular, and metabolic information&#xD;
      on the affected brain at an earlier stage than does conventional structural MRI. The overall&#xD;
      aim of the current proposal is to obtain a better understanding in the neuronal mechanisms&#xD;
      that underlie cognitive decline in DM2 and the putative prediabetic condition the metabolic&#xD;
      syndrome (MetS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Diabetes mellitus type 2 (DM2) is a common chronic metabolic disorder that affects 4.1% of&#xD;
      the Dutch population. In addition to vascular disease, DM2 is associated with structural&#xD;
      brain changes visible on MRI, accelerated cognitive decline, and dementia in older&#xD;
      individuals. The exact pathophysiological mechanisms underlying cognitive decrements in DM2&#xD;
      still remain to be elucidated. The 'metabolic syndrome' (MetS), defined as a cluster of&#xD;
      cardiovascular risk factors (including obesity, hypertension, and dyslipidemia) is often&#xD;
      considered a prediabetic condition. Individuals with MetS display similar cognitive&#xD;
      decrements as do DM2 patients, but do not share the severity of brain injury. It has been&#xD;
      indicated that in prediabetic MetS, cognitive problems precede structural brain changes, and&#xD;
      that MetS and DM2 affect the brain through a shared mechanism in which vascular co-morbidity&#xD;
      is essential.&#xD;
&#xD;
      The primary objectives are defined according to a hierarchical design: i) to tailor and apply&#xD;
      multi-parametric, functional MRI techniques to identify cerebral abnormalities (cerebral&#xD;
      biomarkers) in DM2 and MetS; ii) to investigate which cerebral biomarkers are shared and&#xD;
      differ between DM2 and MetS; iii) to assess whether these cerebral biomarkers are associated&#xD;
      with cognitive decrements.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Functional and structural connectivity relationships of multiple brain regions and biomarkers of brain alterations</measure>
    <time_frame>subjects will be assessed once (on 1 day)</time_frame>
    <description>Differences in macro-structural, micro-structural, and metabolic concentrations between patients and healthy controls will be evaluated. These MRI measures include volumetric characteristics (e.g. hyper-intensities, white matter lesions, atrophy), quantitative measures (e.g. T2 relaxation times, mean diffusivity, fractional anisotropy), functional characteristics (e.g. activated regions, cerebral blood flow), metabolic characteristics (e.g. concentration of metabolites), network properties (e.g. functional and structural connectivity, graph-theoretical measures).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anthropometrics</measure>
    <time_frame>subjects will be assessed once (on 1 day)</time_frame>
    <description>Simple anthropometric measurements will include: Body mass index will be calculated as the weight (kg) divided by the square of the height (m). Waist circumference (WC) will be taken as the minimum circumference between the umbilicus and xiphoid process and measured to the nearest 0.5 cm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mental health</measure>
    <time_frame>subjects will be assessed once (on 1 day)</time_frame>
    <description>For assessment of mental health, specifically depression, the Cambridge Mental Disorders of the Elderly Examination will be used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lifestyle</measure>
    <time_frame>subjects will be assessed once (on 1 day)</time_frame>
    <description>Lifestyle specifics, including alcohol consumption, smoking behavior and mobility will be obtained through a questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular risk factors</measure>
    <time_frame>subjects will be assessed once (on 1 day)</time_frame>
    <description>Blood samples will be assessed for:&#xD;
Fasting circulating levels of glucose, albumin, creatinin, total cholesterol, LDL- and HDL-cholesterol, triglycerides, HbA1c and uric acid.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">106</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <condition>Metabolic Syndrome X</condition>
  <condition>Mild Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>Diabetes mellitus type 2 (DM2)</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>metabolic syndrome (MetS)</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy controls</arm_group_label>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Matched subjects aged 40-75 years with Diabetes mellitus type 2, metabolic syndrome, and&#xD;
        healthy controls&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Subjects aged 40-75 years&#xD;
&#xD;
          -  Subjects enrolled in the existing 'Maastricht Study' (M-Study)&#xD;
&#xD;
          -  Subjects gave written consent to be approached for additional research&#xD;
&#xD;
          -  Subjects belongs to the 20% of the worst and 20% of the best performing (as based on&#xD;
             neuropsychological cognitive testing (Stroop color-word test, 15 word learning test,&#xD;
             and Delayed recall and recognition 15 word learning test)&#xD;
&#xD;
        Individuals Diabetes type 2:&#xD;
&#xD;
        - Fasting blood glucose ≥ 7.0 mmol/l, after an oral glucose tolerance test (OGTT)blood&#xD;
        glucose ≥ 11.1 mmol/l or used oral glucose-lowering medication or insulin&#xD;
&#xD;
        Metabolic syndrome:&#xD;
&#xD;
          -  Participants should meet three out of 5 of the following criteria [8]:&#xD;
&#xD;
               1. Waist circumference &gt; 88 cm (women), &gt; 102 cm (men)&#xD;
&#xD;
               2. Triglycerides ≥ 1.7 mmol/l&#xD;
&#xD;
               3. HDL cholesterol &lt; 1.3 mmol/l (women), &lt; 1.0 mmol/l (men)&#xD;
&#xD;
               4. Blood pressure ≥ 130/85 mmHg (or medication)&#xD;
&#xD;
               5. Fasting blood glucose ≥ 6.1 mmol/l, after an OGTT blood glucose ≥ 7.8 mmol/l&#xD;
&#xD;
                  Control participants:&#xD;
&#xD;
          -  Those who fulfilled no more than 1 criterium of the metabolic syndrome, no DM2.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Contra-indications for MRI examination (e.g. pacemaker; neurostimulator; medication&#xD;
             pump; cochlear or hearing implant; tattoos or other items that cannot be removed and&#xD;
             include metal parts (for instance from operations in the past); metal splinter in the&#xD;
             eye; pregnancy and claustrophobia; brain vessel clamps; denture, which contains&#xD;
             magnets).&#xD;
&#xD;
          -  Psychiatric co-morbidity and inability to perform the functional MRI tests.&#xD;
&#xD;
          -  Incomplete cognitive assessment data&#xD;
&#xD;
          -  Diabetes mellitus type 1 (DM1)&#xD;
&#xD;
          -  Subjects who are not belonging to the 20% of the worst and 20% of the best performing&#xD;
             individuals (as based on neuropsychological cognitive testing (Stroop color-word test,&#xD;
             15 word learning test, and Delayed recall and recognition 15 word learning test).&#xD;
&#xD;
          -  Last visit of the subjects to the M-Study should be less than one year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jacobus FA Jansen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <zip>6202 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <results_reference>
    <citation>van Bussel FC, Backes WH, Hofman PA, van Oostenbrugge RJ, Kessels AG, van Boxtel MP, Schram MT, Stehouwer CD, Wildberger JE, Jansen JF. On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes. Diabetes Care. 2015 May;38(5):876-82. doi: 10.2337/dc14-2043. Epub 2015 Feb 17.</citation>
    <PMID>25690006</PMID>
  </results_reference>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>June 6, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <last_update_submitted>April 9, 2015</last_update_submitted>
  <last_update_submitted_qc>April 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 10, 2015</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>Diabetes Mellitus</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Cognitive Dysfunction</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/NCT01705210
org study id: NL34329.068.10 / METC 10-2-023
secondary id: 916.11.059
nct id: NCT01705210
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The exact neuronal mechanism underlying the cognitive decline associated with diabetes
      mellitus type 2 (DM2) still remains to be elucidated. Multi-parametric functional MRI can
      potentially provide functional, micro-structural, micro-vascular, and metabolic information
      on the affected brain at an earlier stage than does conventional structural MRI. The overall
      aim of the current proposal is to obtain a better understanding in the neuronal mechanisms
      that underlie cognitive decline in DM2 and the putative prediabetic condition the metabolic
      syndrome (MetS).
Diabetes mellitus type 2 (DM2) is a common chronic metabolic disorder that affects 4.1% of
      the Dutch population. In addition to vascular disease, DM2 is associated with structural
      brain changes visible on MRI, accelerated cognitive decline, and dementia in older
      individuals. The exact pathophysiological mechanisms underlying cognitive decrements in DM2
      still remain to be elucidated. The 'metabolic syndrome' (MetS), defined as a cluster of
      cardiovascular risk factors (including obesity, hypertension, and dyslipidemia) is often
      considered a prediabetic condition. Individuals with MetS display similar cognitive
      decrements as do DM2 patients, but do not share the severity of brain injury. It has been
      indicated that in prediabetic MetS, cognitive problems precede structural brain changes, and
      that MetS and DM2 affect the brain through a shared mechanism in which vascular co-morbidity
      is essential.

      The primary objectives are defined according to a hierarchical design: i) to tailor and apply
      multi-parametric, functional MRI techniques to identify cerebral abnormalities (cerebral
      biomarkers) in DM2 and MetS; ii) to investigate which cerebral biomarkers are shared and
      differ between DM2 and MetS; iii) to assess whether these cerebral biomarkers are associated
      with cognitive decrements.
observational model: Cohort
time perspective: Cross-Sectional
measure: Functional and structural connectivity relationships of multiple brain regions and biomarkers of brain alterations
time frame: subjects will be assessed once (on 1 day)
description: Differences in macro-structural, micro-structural, and metabolic concentrations between patients and healthy controls will be evaluated. These MRI measures include volumetric characteristics (e.g. hyper-intensities, white matter lesions, atrophy), quantitative measures (e.g. T2 relaxation times, mean diffusivity, fractional anisotropy), functional characteristics (e.g. activated regions, cerebral blood flow), metabolic characteristics (e.g. concentration of metabolites), network properties (e.g. functional and structural connectivity, graph-theoretical measures).
measure: Anthropometrics
time frame: subjects will be assessed once (on 1 day)
description: Simple anthropometric measurements will include: Body mass index will be calculated as the weight (kg) divided by the square of the height (m). Waist circumference (WC) will be taken as the minimum circumference between the umbilicus and xiphoid process and measured to the nearest 0.5 cm.
measure: Mental health
time frame: subjects will be assessed once (on 1 day)
description: For assessment of mental health, specifically depression, the Cambridge Mental Disorders of the Elderly Examination will be used.
measure: Lifestyle
time frame: subjects will be assessed once (on 1 day)
description: Lifestyle specifics, including alcohol consumption, smoking behavior and mobility will be obtained through a questionnaire.
measure: Cardiovascular risk factors
time frame: subjects will be assessed once (on 1 day)
description: Blood samples will be assessed for:
Fasting circulating levels of glucose, albumin, creatinin, total cholesterol, LDL- and HDL-cholesterol, triglycerides, HbA1c and uric acid.
arm group label: Diabetes mellitus type 2 (DM2)
arm group label: metabolic syndrome (MetS)
arm group label: healthy controls
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jacobus FA Jansen, PhD
role: Principal Investigator
affiliation: Maastricht University Medical Center
facility: 
country: Netherlands
citation: van Bussel FC, Backes WH, Hofman PA, van Oostenbrugge RJ, Kessels AG, van Boxtel MP, Schram MT, Stehouwer CD, Wildberger JE, Jansen JF. On the interplay of microvasculature, parenchyma, and memory in type 2 diabetes. Diabetes Care. 2015 May;38(5):876-82. doi: 10.2337/dc14-2043. Epub 2015 Feb 17.
PMID: 25690006
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Metabolic Syndrome
mesh term: Diabetes Mellitus, Type 2
mesh term: Cognitive Dysfunction