Type2 DiabetesMetabrainNCT05277558
Brain Health in Youth With Normal Weight, Overweight and Obesity at Risk for Type 2 Diabetes (T2D)
An observational study of Type2 Diabetes and Type 2 Diabetes Mellitus in Obese, run by Washington University School of Medicine at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Type2 Diabetes, Type 2 Diabetes Mellitus in Obese, Dysglycemia
- What is being tested?
- Observational
- Type of treatment
- Pill or oral medicine
- How many people
- 117 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 May 2022to 31 Oct 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
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.
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Angela Akar, BS, CCRC, 412-692-5928, angela.akar@chp.edu
Silva Arslanian, MD
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Samantha Ranck, MSW, MA, 314-362-6514, blankens@wustl.edu
Kaeli Spight, 314-362-4721, kspight@wustl.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Type2 Diabetes, Type 2 Diabetes Mellitus in Obese, Dysglycemia, Microvascular Complications, Brain Structure, Obesity, Childhood
- Being tested
- Observational
- Keywords
- Brain, Health, Youth, Type 2 Diabetes Mellitus, overweight, obesity
- Medical subject headings
- Pediatric Obesity, Inflammation, Insulin Resistance, Cognitive Dysfunction, Diabetes Mellitus, Type 2, Overweight, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObservationalOther
Investigators are observing brain health over time (21 months) in these groups
| Study group | Role | What they receive |
|---|---|---|
| Normal Weight-Normal Glucose Tolerant (NW-NGT) | (1) a group that is the normal weight (BMI<85th%) and has normal glucose tolerance (NW-NGT) Receives: 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) Receives: 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). Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 21 months - Visit 1 and Visit 2 are 21 months apart
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2022
- Study start24 May 2022
- Primary completion31 Oct 2026 (estimated)
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type2 DiabetesStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 117 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tamara A Hershey, PhD, Principal investigator, Washington University School of MedicineSilva Arslanian, MD, Principal investigator, UPMC Children's Hospital of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05277558
- Sponsor's protocol ID
- 202107019
- Other IDs
- 1R01DK126826-01A1
- Acronym
- Metabrain
- Status last verified
- Dec 2025
- First submitted
- 11 Feb 2022
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Health Across the Metabolic Continuum in Youth at Risk for Type 2 Diabetes (T2D)
- ClinicalTrials.gov ID
- NCT05277558
- Acronym / sponsor ID
- Metabrain / 202107019
- Conditions
- Type2 Diabetes, Type 2 Diabetes Mellitus in Obese, Dysglycemia, Microvascular Complications, Brain Structure, Obesity, Childhood
- Keywords
- Brain, Health, Youth, Type 2 Diabetes Mellitus, overweight, obesity
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 117 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 24 May 2022 (actual)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 14 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Normal Weight-Normal Glucose Tolerant (NW-NGT) | – | Other: Observational(1) a group that is the normal weight (BMI<85th%) and has normal glucose tolerance (NW-NGT) |
| Overweight and/or obese and has normal glucose tolerance (O-NGT) | – | Other: Observational(2) a group that is overweight and/or obese (BMI >85th%) and has normal glucose tolerance (O-NGT) |
| Overweight and/or Obese and has dysglycemia (O-DG) | – | Other: Observational(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). |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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.
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ObservationalInvestigators are observing brain health over time (21 months) in these groups | Other | 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) |
Primary outcome
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.
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.
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.
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
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tamara A Hershey, PhD principal investigator
Washington University School of Medicine
Silva Arslanian, MD principal investigator
UPMC Children's Hospital of Pittsburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type2 Diabetes and Type 2 Diabetes Mellitus in Obese, run by Washington University School of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mary Borgschulte, RN, BSN, CDE (314-952-8195, Mary.b@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
hippocampal volume (time frame: 21 months - Visit 1 and Visit 2 are 21 months apart). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.