- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05277558
Brain Health in Youth With Normal Weight, Overweight and Obesity at Risk for Type 2 Diabetes (T2D) (Metabrain)
April 10, 2024 updated by: Tamara Hershey, Washington University School of Medicine
Brain Health Across the Metabolic Continuum in Youth 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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Observational
Enrollment (Estimated)
117
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Kaeli Spight
- Phone Number: 314-362-4721
- Email: kspight@wustl.edu
Study Contact Backup
- Name: Mary Borgschulte, RN, BSN, CDE
- Phone Number: 314-952-8195
- Email: Mary.b@wustl.edu
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine
-
Contact:
- Kaeli Spight
- Phone Number: 314-362-4721
- Email: kspight@wustl.edu
-
Contact:
- Samantha Ranck, MSW, MA
- Phone Number: 314-362-6514
- Email: blankens@wustl.edu
-
Principal Investigator:
- Tamara G Hershey, PhD
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15224
- Recruiting
- UPMC Children's Hospital of Pittsburgh
-
Contact:
- Angela Akar, BS, CCRC
- Phone Number: 412-692-5928
- Email: angela.akar@chp.edu
-
Principal Investigator:
- Silva Arslanian, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years to 17 years (Child)
Accepts Healthy Volunteers
Yes
Sampling Method
Non-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.
Description
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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Normal Weight-Normal Glucose Tolerant (NW-NGT)
(1) a group that is the normal weight (BMI<85th%) and has normal glucose tolerance (NW-NGT)
|
Investigators are observing brain health over time (21 months) in these groups
|
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)
|
Investigators are observing brain health over time (21 months) in these groups
|
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).
|
Investigators are observing brain health over time (21 months) in these groups
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
21 months - Visit 1 and Visit 2 are 21 months apart
|
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.
|
21 months - Visit 1 and Visit 2 are 21 months apart
|
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.
|
21 months - Visit 1 and Visit 2 are 21 months apart
|
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
|
21 months - Visit 1 and Visit 2 are 21 months apart
|
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.
|
21 months - Visit 1 and Visit 2 are 21 months apart
|
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.
|
21 months - Visit 1 and Visit 2 are 21 months apart
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Tamara A Hershey, PhD, Washington University School of Medicine
- Principal Investigator: Silva Arslanian, MD, UPMC Children's Hospital of Pittsburgh
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 24, 2022
Primary Completion (Estimated)
October 31, 2026
Study Completion (Estimated)
October 31, 2027
Study Registration Dates
First Submitted
February 11, 2022
First Submitted That Met QC Criteria
March 11, 2022
First Posted (Actual)
March 14, 2022
Study Record Updates
Last Update Posted (Actual)
April 11, 2024
Last Update Submitted That Met QC Criteria
April 10, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Glucose Metabolism Disorders
- Metabolic Diseases
- Neurocognitive Disorders
- Endocrine System Diseases
- Overnutrition
- Nutrition Disorders
- Body Weight
- Hyperinsulinism
- Cognition Disorders
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Obesity
- Inflammation
- Pediatric Obesity
- Cognitive Dysfunction
- Insulin Resistance
- Overweight
Other Study ID Numbers
- 202107019
- 1R01DK126826-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
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.
IPD Sharing Time Frame
within 12 months of end of data collection, data entry, quality control and image processing
IPD Sharing Access Criteria
PI will need to request data for legitimate scientific purpose.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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