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NCT Number: NCT05277558

Brain Health in Youth With Normal Weight, Overweight and Obesity at Risk for Type 2 Diabetes (T2D)

Investigators propose to study youth across the spectrum of body mass index (BMI) and dysglycemia. This approach will allow investigators to disentangle the relationship of key features of type 2 diabetes (T2D) risk (e.g. obesity) with intermediary physiologic changes (e.g. insulin resistance, inflammation, β-cell dysfunction and dysglycemia) that pose a risk for the brain. Investigators will determine which of these factors are most associated with differences in brain structure and function among groups, over time, and how these effects differ from normal neurodevelopment.

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Key information

Conditions

Type2 Diabetes Body Weight Brain Structure Cognition Disorders Cognitive Decline Cognitive Dysfunction Diabetes Mellitus Diabetes Mellitus, Type 2 Diabetes in Adolescence Dysglycemia Endocrine System Diseases Glucose Metabolism Disorders Hyperinsulinism Inflammation Insulin Resistance Mental Disorders Metabolic Diseases Microvascular Complications Neurocognitive Disorders Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity, Childhood Overnutrition Overweight Overweight, Childhood Pathologic Processes Pathological Conditions, Signs and Symptoms Pediatric Obesity Signs and Symptoms Type 2 Diabetes Mellitus in Obese

Age range

12 year–17 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Washington University School of Medicine, St Louis, Missouri, United States

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About this study

Investigators will study three groups of pubertal youth, ages 12-17 yrs old (n=31 each): a group with normal weight and normal glucose tolerance (NW-NGT), a group with overweight/obesity and normal glucose tolerance (O-NGT), and a group with overweight/obesity and dysglycemia (O-DG). Groups will be comparable in age, sex, race/ethnicity, and socio-economic status (SES). Brain structure and function will be examined in all groups using magnetic resonance imaging (MRI) and cognitive tests at study entry (time 1/baseline), and after 21 months (time 2), focusing on a limited number of key outcome variables known to be consistently impaired in obesity or T2D. Targeted MRI measures will be regional volumes (e.g. hippocampus), neuroinflammation via restricted ratio from diffusion basis spectrum imaging (DBSI); hippocampus and white matter tracts), whole-brain cerebral blood flow via arterial spin labeling (ASL). Targeted cognitive measures will be delayed memory, processing speed, and executive function. The ultimate goal of this study is to determine how metabolic factors during neurodevelopment set the stage for the potentially profound, long-term impact of T2D on the brain and its functions. Given that the disease occurs at a time when brains are undergoing dramatic developmental processes, the aggressive nature of youth-onset T2D progression and complications in other organ systems, these results may provide guidance and justification for longer follow-up, interventional and/or mechanistic studies, and have important clinical implications.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 12-17 yrs. old at visit 1, 12-19 yrs. old at visit 2, Tanner II or above (determined through an exam by a pediatric endocrinologist or certified nurse practitioner trained in pediatric endocrinology), otherwise healthy except for obesity, <450 lbs. (due to MRI scanner limits), able and willing to lie flat within the MRI scanner and do cognitive testing, fluent in English.

Exclusion criteria

  • Syndromic obesity, history of bariatric surgery, insulin treatment (metformin allowed if < 6 months) for T2D, contraindications for MRI (metal, claustrophobia), braces, pregnant (pregnancy test will be done on post-menarchal girls) or breastfeeding, inability to participate in cognitive testing due to sensory or language issues, intellectual disability, special education, pharmacologic treatment for Attention Deficit Hyperactivity Disorder (ADHD), prematurity (<36 weeks gestation), complications at birth, neurologic co-morbidities (e.g., seizures, stroke, head injury with >10 min loss of consciousness), significant psychiatric disorders (e.g., schizophrenia, bipolar disorder, current major depression), taking psychoactive medications (e.g., antipsychotics) that would interfere with testing or reporting illegal drug use. Self-reported smoking and alcohol use and length of time with obesity will be assessed by history (although these measures may not be fully reliable).

Treatment and study plan

Observational

Other

Investigators are observing brain health over time (21 months) in these groups

Primary outcomes

  1. hippocampal volume

    Time frame: 21 months - Visit 1 and Visit 2 are 21 months apart

    To determine hippocampal volumes, investigators will use the validated, objective and semi-automatic segmentation program Automated MRI Brain Volumetry System (volBrain). Hippocampal volumes will be obtained for each subject at each visit for primary analyses. Left and right volumes will be averaged, since lateralized findings are not hypothesized.

  2. restricted fraction

    Time frame: 21 months - Visit 1 and Visit 2 are 21 months apart

    Investigators will use Diffusion Basis Spectrum Imaging (DBSI) models on diffusion weighted images (DWI) to assess restricted fraction within the hippocampus and throughout white matter tracts.

  3. Whole brain cerebral blood flow

    Time frame: 21 months - Visit 1 and Visit 2 are 21 months apart

    Pseudo-continuous arterial spin labeling (pCASL) will be used to measure cerebral blood flow (CBF) implemented with an arterial spin labeling (ASL) sequence 228 and volume navigators (vNavs) to minimize motion artifact. Global CBF across pairs of frames will be scaled additively to the median value. Investigators will assess the number of voxels that statistically deviate from a normative value ('distributed deviating voxels') and compared between groups.

  4. Declarative Memory

    Time frame: 21 months - Visit 1 and Visit 2 are 21 months apart

    Investigators will use the total score from the Paired Associates Memory Test, an experimental cognitive task measuring delayed declarative memory

  5. Processing speed

    Time frame: 21 months - Visit 1 and Visit 2 are 21 months apart

    Investigators will use the raw scores from the NIH Toolbox Pattern Comparison Processing Speed task.

  6. Executive Function

    Time frame: 21 months - Visit 1 and Visit 2 are 21 months apart

    Investigators will use an average of the (z scores) from the NIH Toolbox Flanker Inhibitory Control & Attention, Dimensional Change Card Sort and List Sorting tasks.

Study contacts

Contact information is provided by the study sponsor or research team.

Kaeli Spight

CONTACT

[email protected]

314-362-4721

Mary Borgschulte, RN, BSN, CDE

CONTACT

[email protected]

314-952-8195

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Official study title

Brain Health Across the Metabolic Continuum in Youth at Risk for Type 2 Diabetes (T2D)

Acronym: Metabrain

Important dates

Study start
2022
Primary completion
2026
Study completion
2027
First posted
Mar 14, 2022
Registry last updated
Dec 18, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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