Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cognition and Magnetic Resonance Imaging of Brain Inflammation in Obesity (NIFOB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04116229
Recruitment Status : Suspended (Temporarily paused due to COVID-19 and expected to resume. This is not a suspension of IRB approval.)
First Posted : October 4, 2019
Last Update Posted : June 2, 2020
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Sarah Eisenstein, Washington University School of Medicine

Brief Summary:
The rate of obesity in the United States is high and is a risk factor for concurrent cognitive impairment and, in late life, dementias such as Alzheimer's disease. In order to prevent or reduce cognitive impairment, the mechanism underlying the link between obesity and cognitive impairment must be understood. The current study aims to provide preliminary data on whether brain inflammation occurs in obesity and relates to cognitive deficits using magnetic resonance neuroimaging and cognitive testing. It is hypothesized that obese individuals will have greater brain inflammation and lower cognitive function compared to normal-weight individuals. Further, it is predicted that brain inflammation will relate to cognitive function and plasma indicators of inflammation in obese individuals.

Condition or disease Intervention/treatment
Obesity Procedure: Oral glucose tolerance test Behavioral: Cognitive testing Procedure: Magnetic resonance imaging

Detailed Description:
Initially, normal-weight or obese potential participants are screened by a phone interview that assesses medical history. Obtainment of informed consent and further screening occurs on the day of the study visit. Participants then undergo a 2 hour oral glucose tolerance test (OGTT) including blood draws for metabolic and inflammatory marker levels in plasma. Lunch is then provided. Participants are then administered 30 minute computer-based cognitive testing from the NIH Toolbox Cognition Battery. After cognitive testing, participants undergo 1.5 hour magnetic resonance imaging (MRI) that includes structural, diffusion tensor, and functional MR imaging.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Neuroinflammation in Obesity
Actual Study Start Date : March 19, 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Normal-weight
Participants who have a body mass index within the normal-weight category.
Procedure: Oral glucose tolerance test
After 8 hours fasting overnight, an intravenous catheter is placed in the arm or hand for blood draws. Participants drink 75 grams of an oral glucose drink after baseline blood samples are drawn. More blood draws occur at 10, 20, 30, 60 and 120 min post-glucose drink.

Behavioral: Cognitive testing
For approximately 40 minutes, participants are assessed for cognitive function using computer-based tests available from the NIH Toolbox Cognitive Battery (Weintraub et al., 2013), including attention and executive functioning, episodic memory, working memory, language, processing speed, and immediate recall.

Procedure: Magnetic resonance imaging
Magnetic resonance imaging (MRI) scans will be performed in a 3 Tesla MRI scanner over 1.5 hours. Participants will be asked to lay down flat on their backs and to try to stay still throughout the MRI scan. The participant will wear MRI-safe headphones to block out noise due to the MRI scans. Participant comfort will be verbally checked on throughout the scan and the participant will be provided with a 'squeeze ball' to signal the MRI technician that they want to get out of the scanner immediately.

Obese
Participants who have a body mass index within the obese category.
Procedure: Oral glucose tolerance test
After 8 hours fasting overnight, an intravenous catheter is placed in the arm or hand for blood draws. Participants drink 75 grams of an oral glucose drink after baseline blood samples are drawn. More blood draws occur at 10, 20, 30, 60 and 120 min post-glucose drink.

Behavioral: Cognitive testing
For approximately 40 minutes, participants are assessed for cognitive function using computer-based tests available from the NIH Toolbox Cognitive Battery (Weintraub et al., 2013), including attention and executive functioning, episodic memory, working memory, language, processing speed, and immediate recall.

Procedure: Magnetic resonance imaging
Magnetic resonance imaging (MRI) scans will be performed in a 3 Tesla MRI scanner over 1.5 hours. Participants will be asked to lay down flat on their backs and to try to stay still throughout the MRI scan. The participant will wear MRI-safe headphones to block out noise due to the MRI scans. Participant comfort will be verbally checked on throughout the scan and the participant will be provided with a 'squeeze ball' to signal the MRI technician that they want to get out of the scanner immediately.




Primary Outcome Measures :
  1. Brain Inflammation Metrics in Obese and Normal-weight Individuals as Measured by Magnetic Resonance Image-based Diffusion Basis Spectrum Imaging (DBSI) [ Time Frame: 1.5 hours at the end of one (up to) 8 hour study day that includes all outcome measures ]
    Diffusion Basis Spectrum Imaging (Cross and Song, 2017) is a computational method that will be applied to diffusion tensor images of the brain to estimate putative inflammation-related markers including cellularity and edema in obese and normal-weight individuals. DBSI metrics are quantitative but unitless. Cellularity and edema fractions of the total diffusion signal (including axial, radial, restricted (cellularity) and hindered (edema)) will be estimated.

  2. Cognitive Function in Obese and Normal-weight Individuals as Measured by the National Institutes of Health (NIH) Toolbox Cognitive Battery [ Time Frame: 40 minutes during one (up to) 8 hour study day that includes all outcome measures; after OGTT and prior to MRI ]
    Cognitive performance including fluid and crystallized cognition composite T-scores from computer-based NIH Cognitive Toolbox assessments (Weintraub et al., 2013) will be assessed in obese and normal-weight individuals. These T-scores will include scores from tasks that assess attention and executive functioning, episodic memory, working memory, language, processing speed, and immediate recall (see NIH Toolbox Cognitive Battery website).

  3. Peripheral Inflammation in Obese and Normal-weight Individuals as Measured by Plasma Assays [ Time Frame: 5 minutes during one (up to) 8 hour study day that includes all outcome measures; blood draw prior to OGTT ]
    Plasma will be isolated from whole blood prior to the 2 hour oral glucose tolerance test (OGTT) and frozen for laboratory analyses. Peripheral inflammatory markers of interest including interleukin (IL)-6, IL-1B, total adiponectin, tumor necrosis factor alpha, C-C Motif Chemokine Ligand 2, toll receptor 4, and C-reactive protein will be measured using radioimmunoassay and enzyme-linked immunosorbent assays in a wet laboratory.


Secondary Outcome Measures :
  1. Metabolic Markers in Plasma in Obese and Normal-weight individuals. [ Time Frame: 2 hours during one (up to) 8 hour study day that includes all outcome measures; first activity of the study day ]
    Plasma will be isolated from whole blood drawn at each OGTT time point and frozen. Insulin sensitivity and pancreatic beta function will be quantified using the oral glucose minimal model, which requires C-peptide, insulin, and glucose levels in plasma at fasting and throughout the 2 hour OGTT (Breda et al., 2001). Peripheral metabolic markers including C-peptide, insulin, and glucose levels in plasma will be measured for each timepoint of the OGTT using electrochemiluminescence, hexokinase ultraviolet method, and radioimmunoassay in a wet laboratory.


Biospecimen Retention:   Samples With DNA
Whole blood and plasma.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Participants will be selected from the St. Louis, Missouri metropolitan area community.
Criteria

Inclusion Criteria:

  • Non-obese (body mass index = 18 - 25 kg/m^2) or Obese (body mass index ≥ 30 kg/m^2
  • Any race or ethnicity
  • Native English speaker

Exclusion Criteria:

  • Past or current diabetes
  • Current psychotropic medication use
  • Past or current neurological illness
  • Past or current substance or alcohol misuse
  • Past or current mental illness
  • Current binge eating disorder
  • Magnetic resonance imaging contraindications
  • Pregnancy
  • Currently lactating
  • Tobacco use within past month
  • Over 350 lb

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04116229


Locations
Layout table for location information
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Layout table for investigator information
Principal Investigator: Sarah A Eisenstein, PhD Washington University School of Medicine
Additional Information:
Publications:
Layout table for additonal information
Responsible Party: Sarah Eisenstein, Assistant Professor, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT04116229    
Other Study ID Numbers: 201805053
P30DK020579 ( U.S. NIH Grant/Contract )
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: June 2, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: The project is still in early stages of recruiting and data collection.Data will be shared if it is included in a publication.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sarah Eisenstein, Washington University School of Medicine:
Obesity
Inflammation
Cognitive impairment
Neuroimaging
Magnetic resonance imaging
Additional relevant MeSH terms:
Layout table for MeSH terms
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms