Functional MRI Biomarkers of Cognitive Decrements in Diabetes

• ClinicalTrials.gov Identifier: NCT01705210
• Recruitment Status: Completed
• First Posted: October 12, 2012
• Last Update Posted: April 10, 2015
• Sponsor: Maastricht University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development; Netherlands Organisation for Scientific Research
• Information provided by (Responsible Party): Maastricht University Medical Center

Tracking Information

• First Submitted Date: June 6, 2012
• First Posted Date: October 12, 2012
• Last Update Posted Date: April 10, 2015
• Study Start Date: May 2012
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 11, 2012)

Functional and structural connectivity relationships of multiple brain regions and biomarkers of brain alterations [ Time Frame: subjects will be assessed once (on 1 day) ]

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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 11, 2012)

• Anthropometrics [ Time Frame: subjects will be assessed once (on 1 day) ]
  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.
• Mental health [ Time Frame: subjects will be assessed once (on 1 day) ]
  For assessment of mental health, specifically depression, the Cambridge Mental Disorders of the Elderly Examination will be used.
• Lifestyle [ Time Frame: subjects will be assessed once (on 1 day) ]
  Lifestyle specifics, including alcohol consumption, smoking behavior and mobility will be obtained through a questionnaire.
• Cardiovascular risk factors [ Time Frame: subjects will be assessed once (on 1 day) ]
  Blood samples will be assessed for: Fasting circulating levels of glucose, albumin, creatinin, total cholesterol, LDL- and HDL-cholesterol, triglycerides, HbA1c and uric acid.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Functional MRI Biomarkers of Cognitive Decrements in Diabetes
• Official Title: Functional MRI Biomarkers of Cognitive Decrements in Diabetes
• Brief Summary: 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).

Detailed Description

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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Probability Sample
• Study Population: Matched subjects aged 40-75 years with Diabetes mellitus type 2, metabolic syndrome, and healthy controls

Condition

• Diabetes Mellitus, Type 2
• Metabolic Syndrome X
• Mild Cognitive Impairment

• Intervention: Not Provided

Study Groups/Cohorts

• Diabetes mellitus type 2 (DM2)
• metabolic syndrome (MetS)
• healthy controls

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 9, 2015): 106
• Original Estimated Enrollment (submitted: October 11, 2012): 132
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

• Subjects aged 40-75 years
• Subjects enrolled in the existing 'Maastricht Study' (M-Study)
• Subjects gave written consent to be approached for additional research
• Subjects belongs to the 20% of the worst and 20% of the best performing (as based on neuropsychological cognitive testing (Stroop color-word test, 15 word learning test, and Delayed recall and recognition 15 word learning test)

Individuals Diabetes type 2:

- Fasting blood glucose ≥ 7.0 mmol/l, after an oral glucose tolerance test (OGTT)blood glucose ≥ 11.1 mmol/l or used oral glucose-lowering medication or insulin

Metabolic syndrome:

• Participants should meet three out of 5 of the following criteria [8]:

  1. Waist circumference > 88 cm (women), > 102 cm (men)
  2. Triglycerides ≥ 1.7 mmol/l
  3. HDL cholesterol < 1.3 mmol/l (women), < 1.0 mmol/l (men)
  4. Blood pressure ≥ 130/85 mmHg (or medication)

  5. Fasting blood glucose ≥ 6.1 mmol/l, after an OGTT blood glucose ≥ 7.8 mmol/l

     Control participants:

• Those who fulfilled no more than 1 criterium of the metabolic syndrome, no DM2.

Exclusion criteria:

• Contra-indications for MRI examination (e.g. pacemaker; neurostimulator; medication pump; cochlear or hearing implant; tattoos or other items that cannot be removed and include metal parts (for instance from operations in the past); metal splinter in the eye; pregnancy and claustrophobia; brain vessel clamps; denture, which contains magnets).
• Psychiatric co-morbidity and inability to perform the functional MRI tests.
• Incomplete cognitive assessment data
• Diabetes mellitus type 1 (DM1)
• Subjects who are not belonging to the 20% of the worst and 20% of the best performing individuals (as based on neuropsychological cognitive testing (Stroop color-word test, 15 word learning test, and Delayed recall and recognition 15 word learning test).
• Last visit of the subjects to the M-Study should be less than one year

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT01705210
• Other Study ID Numbers: NL34329.068.10 / METC 10-2-023; 916.11.059 ( Other Grant/Funding Number: NWO/ZonMW VENI )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Maastricht University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Maastricht University Medical Center
• Original Study Sponsor: Same as current

Collaborators

• ZonMw: The Netherlands Organisation for Health Research and Development
• Netherlands Organisation for Scientific Research

Investigators

• Principal Investigator: Jacobus FA Jansen, PhD; Maastricht University Medical Center

• PRS Account: Maastricht University Medical Center
• Verification Date: April 2015