Cognition and Magnetic Resonance Imaging of Brain Inflammation in Obesity

Obesity Clinical Trial

— NIFOB  

Official title:

Neuroinflammation in Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04116229
• Other study ID #: 201805053
• Secondary ID: P30DK020579
• Status: Completed
• Phase: N/A
• Start date: March 19, 2019
• Est. completion date: October 30, 2020

Study information

• Verified date: March 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 30, 2020
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

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.

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Breda E, Cavaghan MK, Toffolo G, Polonsky KS, Cobelli C. Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity. Diabetes. 2001 Jan;50(1):150-8. doi: 10.2337/diabetes.50.1.150. — View Citation

Cross AH, Song SK. "A new imaging modality to non-invasively assess multiple sclerosis pathology". J Neuroimmunol. 2017 Mar 15;304:81-85. doi: 10.1016/j.jneuroim.2016.10.002. Epub 2016 Oct 8. — View Citation

Weintraub S, Dikmen SS, Heaton RK, Tulsky DS, Zelazo PD, Bauer PJ, Carlozzi NE, Slotkin J, Blitz D, Wallner-Allen K, Fox NA, Beaumont JL, Mungas D, Nowinski CJ, Richler J, Deocampo JA, Anderson JE, Manly JJ, Borosh B, Havlik R, Conway K, Edwards E, Freund L, King JW, Moy C, Witt E, Gershon RC. Cognition assessment using the NIH Toolbox. Neurology. 2013 Mar 12;80(11 Suppl 3):S54-64. doi: 10.1212/WNL.0b013e3182872ded. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain Inflammation Metrics in Obese and Normal-weight Individuals as Measured by Magnetic Resonance Image-based Diffusion Basis Spectrum Imaging (DBSI)	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 in brain white matter tracts.	1.5 hours at the end of one (up to) 8 hour study day that includes all outcome measures
Primary	Cognitive Function in Obese and Normal-weight Individuals as Measured by the National Institutes of Health (NIH) Toolbox Cognitive Battery and DBSI Putative Neuroinflammation Metrics	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). T-scores are corrected for socioeconomic status and their distribution has a mean of 50 and a standard deviation of 10. Higher T-scores indicate better cognitive function. T-scores will be correlated with DBSI-assessed neuroinflammation metrics including restricted fraction (DBSI RF, putative cellularity) and hindered fraction (DBSI HF, putative vasogenic edema) in brain white matter tracts.	40 minutes during one (up to) 8 hour study day that includes all outcome measures; after OGTT and prior to MRI

External Links

•   NIH Toolbox Cognitive Battery description