NCT04116229: NIFOB

Cognition and Magnetic Resonance Imaging of Brain Inflammation in Obesity

Completed NA Results posted Last updated 10 March 2023

What this trial tests

NA trial testing Oral glucose tolerance test in Obesity in 20 participants. Completed in 30 October 2020.

Timeline

19 March 2019

Primary endpoint
30 October 2020

30 October 2020

Quick facts

Lead sponsor	Washington University School of Medicine
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	double
Primary purpose	other
Enrollment	20
Start date	19 March 2019
Primary completion	30 October 2020
Estimated completion	30 October 2020
Sites	1 location across United States

Drugs / interventions tested

• Oral glucose tolerance test — full drug profile →
• Cognitive testing
• Magnetic resonance imaging

Conditions studied

• Obesity — all drugs for Obesity →

Sponsor

Washington University School of Medicine

Who can join

Adults 18 to 75, any sex, with Obesity. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Brain Inflammation Metrics in Obese and Normal-weight Individuals as Measured by Magnetic Resonance Image-based Diffusion Basis Spectrum Imaging (DBSI) Primary · 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 in brain white matter tracts.

DBSI restricted fraction (cellularity)

Group	Value	95% CI
Normal-weight	.0468	± .0024
Obese	.0492	± .0034

DBSI hindered fraction (vasogenic edema)

Group	Value	95% CI
Normal-weight	.176	± .013
Obese	.186	± .014

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 Primary · 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). 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 cognit

Crystallized Cognition

Group	Value	95% CI
Normal-weight	60.3	± 6.9
Obese	53.3	± 9.0

Fluid Cognition

Group	Value	95% CI
Normal-weight	54.4	± 6.7
Obese	59.3	± 7.4

Metabolic Markers in Plasma and Relationships With DBSI Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals. Secondary · Baseline

Fasting plasma insulin, a measure of insulin resistance in which higher levels may reflect greater effort to maintain glucose homeostasis, was measured by radioimmunoassay. Normal fasting plasma insulin levels are \< 25 uU/mL.

Group	Value	95% CI
Normal-weight	5.28	± 3.73
Obese	15.62	± 10.82

Metabolic Markers in Plasma and Relationships With DBSI Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals. Secondary · Baseline

Fasting plasma leptin, a hormone related to adipose tissue mass such that higher levels reflect greater adipose tissue mass, was measured by radioimmunoassay. For body mass index (BMI) in normal-weight (18.5-24.9 kg/m\^2), leptin reference range = 1.8-24.2 ug/L in females and 0.2-7.7 in males. For BMI in individuals with obesity, leptin reference range = 10.6-141 in females and 3.2-135 in males.

Group	Value	95% CI
Normal-weight	19.9	± 13.4
Obese	110	± 49.7

Metabolic Markers in Plasma and Relationships With DBSI Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals. Secondary · Baseline

Fasting plasma ghrelin, a hormone related to hunger in which higher levels may signal the stomach is empty and it is time to eat, was measured by radioimmunoassay. Plasma ghrelin levels tend to be lower in people with obesity. There is no established normal range for fasting plasma ghrelin levels as assessed by radioimmunoassay.

Group	Value	95% CI
Normal-weight	1498.5	± 568.6
Obese	914.8	± 261.7

Metabolic Markers in Plasma and Relationships With DBSI Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals. Secondary · Baseline

Homeostatic measure of insulin resistance (HOMA-IR) where higher scores indicate greater insulin resistance, or diminished maintenance of glucose homeostasis by insulin. HOMA-IR was calculated according to the formula: fasting insulin (uU/L) \* fasting glucose (nmol/L)/22.5 A HOMA-IR score \>2.5 indicates insulin resistance.

Group	Value	95% CI
Normal-weight	1.21	± 0.79
Obese	3.47	± 2.56

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals Secondary · Baseline

Fasting plasma interleukin (IL)-10, an anti-inflammatory cytokine important for immune response. IL-10 was measured using high-sensitive enzyme-linked immuno-absorbent assay (ELISA). Normal reference ranges for IL-10 have not been established and better or worse levels depend on disease state.

Group	Value	95% CI
Normal-weight	1.85	± 1.38
Obese	1.97	± 0.75

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals Secondary · Baseline

Fasting plasma adiponectin, an anti-inflammatory cytokine important for immune response. Adiponectin was measured using radioimmunoassay. Normal reference ranges for adiponectin is 2.5-21.1 ug/mL. Lower levels of adiponectin tend to be associated with worse metabolic health and higher body mass index.

Group	Value	95% CI
Normal-weight	11.3	± 5.6
Obese	10.8	± 4.9

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals Secondary · Baseline

Fasting plasma tumor necrosis factor (TNF)-alpha, a pro-inflammatory cytokine important for systemic inflammation. TNF-alpha was measured using high-sensitive enzyme-linked immuno-absorbent assay (ELISA). Normal TNF-alpha levels range from non-detectable to 8.1 pg/mL and tend to be higher in people with obesity compared to normal-weight.

Group	Value	95% CI
Normal-weight	0.69	± 0.16
Obese	0.84	± 0.16

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals Secondary · Baseline

Fasting plasma monocyte chemoreactant protein (MCP)-1, a pro-inflammatory chemokine important for immune response and inflammation. MCP-1 was measured using enzyme-linked immuno-absorbent assay (ELISA). Normal reference ranges for MCP-1 have not been established but higher levels tend to be associated with higher body mass index.

Group	Value	95% CI
Normal-weight	140.9	± 37
Obese	160.3	± 40.1

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals Secondary · Baseline

Fasting plasma high-sensitive C-reactive protein (CRP), where higher levels may reflect greater low-grade inflammation. High-sensitive CRP was measured using high-sensitive CRP turbidimetry assay. Higher high-sensitive CRP levels may reflect greater risk for cardiovascular disease. Normal range for hs-CRP is usually below 1 mg/L.

Group	Value	95% CI
Normal-weight	1	± 0.8
Obese	4.8	± 3.1

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.