NCT05277558

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
117

participants targeted

Target at P50-P75 for all trials

Timeline
18mo left

Started May 2022

Longer than P75 for all trials

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress73%
May 2022Oct 2027

First Submitted

Initial submission to the registry

February 11, 2022

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 14, 2022

Completed
2 months until next milestone

Study Start

First participant enrolled

May 24, 2022

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2026

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2027

Last Updated

December 18, 2025

Status Verified

December 1, 2025

Enrollment Period

4.4 years

First QC Date

February 11, 2022

Last Update Submit

December 16, 2025

Conditions

Keywords

Brain, Health, Youth, Type 2 Diabetes Mellitus, overweight, obesity

Outcome Measures

Primary Outcomes (6)

  • hippocampal volume

    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.

    21 months - Visit 1 and Visit 2 are 21 months apart

  • restricted fraction

    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.

    21 months - Visit 1 and Visit 2 are 21 months apart

  • Whole brain cerebral blood flow

    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.

    21 months - Visit 1 and Visit 2 are 21 months apart

  • Declarative Memory

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

    21 months - Visit 1 and Visit 2 are 21 months apart

  • Processing speed

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

    21 months - Visit 1 and Visit 2 are 21 months apart

  • Executive Function

    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.

    21 months - Visit 1 and Visit 2 are 21 months apart

Study Arms (3)

Normal Weight-Normal Glucose Tolerant (NW-NGT)

(1) a group that is the normal weight (BMI\<85th%) and has normal glucose tolerance (NW-NGT)

Other: Observational

Overweight and/or obese and has normal glucose tolerance (O-NGT)

(2) a group that is overweight and/or obese (BMI \>85th%) and has normal glucose tolerance (O-NGT)

Other: Observational

Overweight and/or Obese and has dysglycemia (O-DG)

(3) group that is overweight and/or obese (BMI \>85th%) and has dysglycemia (O-DG; fasting plasma glucose ≥100 mg/dl and/or 2-hour glucose ≥140 mg/dl oral glucose tolerance test (OGTT) and laboratory-based HbA1c ≥5.8 and ≤8.0%, if treatment naïve).

Other: Observational

Interventions

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

Normal Weight-Normal Glucose Tolerant (NW-NGT)Overweight and/or Obese and has dysglycemia (O-DG)Overweight and/or obese and has normal glucose tolerance (O-NGT)

Eligibility Criteria

Age12 Years - 17 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
Study Population

Pubertal youth ages 12-17 yrs. will be enrolled in a longitudinal design. Investigators chose to focus on the ages where there is the highest prevalence of impaired glucose tolerance (IGT) and T2D, reducing variability in neurodevelopmental and Tanner stages in the three cohorts. Investigators will follow participants for 21 months to ensure that enough time has passed to see changes in the stated outcome measures.

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

See page 12 of the protocol.

MeSH Terms

Conditions

Pediatric ObesityInflammationInsulin ResistanceCognitive DysfunctionDiabetes Mellitus, Type 2OverweightObesity

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

OvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsPathologic ProcessesHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesCognition DisordersNeurocognitive DisordersMental DisordersDiabetes MellitusEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health CareOutcome and Process Assessment, Health CareQuality of Health CareHealth Services Administration

Study Officials

  • Tamara A Hershey, PhD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR
  • Silva Arslanian, MD

    UPMC Children's Hospital of Pittsburgh

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Mary Borgschulte, RN, BSN, CDE

CONTACT

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 11, 2022

First Posted

March 14, 2022

Study Start

May 24, 2022

Primary Completion (Estimated)

October 31, 2026

Study Completion (Estimated)

October 31, 2027

Last Updated

December 18, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will share

Investigators affirm that data and research resources will be shared. Any shared data will have low re-identification potential. The Research Design \& Biostatistics Group of the investigative team's Washington University's Clinical Translational Science Award (CTSA) provides access to the REDCap database to facilitate secure data sharing with approved investigators within the University as well as with approved collaborators. De-identified MRI scans will be shared with approved investigators through the Central Neuroimaging Data Archive (CNDA), an online, secure image archive system.

Shared Documents
STUDY PROTOCOL
Time Frame
within 12 months of end of data collection, data entry, quality control and image processing
Access Criteria
PI will need to request data for legitimate scientific purpose.

Locations