Clinical trial NCT05277558: Brain Health in Youth With Normal Weight, Overweight and Obesity at Risk for Type 2 Diabetes (T2D)
Official title: Brain Health Across the Metabolic Continuum in Youth at Risk for Type 2 Diabetes (T2D)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Type2 Diabetes
Type 2 Diabetes Mellitus in Obese
Dysglycemia
Microvascular Complications
Brain Structure
Obesity, Childhood
Diabetes in Adolescence
Inflammation
Insulin Resistance
Overweight, Childhood
Cognitive Decline
Keywords: Brain, Health, Youth, Type 2 Diabetes Mellitus, overweight, obesity
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2022-03-14
Enrollment: 117
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: hippocampal volume
timeFrame: 21 months - Visit 1 and Visit 2 are 21 months apart
measure: restricted fraction
timeFrame: 21 months - Visit 1 and Visit 2 are 21 months apart
measure: Whole brain cerebral blood flow
timeFrame: 21 months - Visit 1 and Visit 2 are 21 months apart
measure: Declarative Memory
timeFrame: 21 months - Visit 1 and Visit 2 are 21 months apart
measure: Processing speed
timeFrame: 21 months - Visit 1 and Visit 2 are 21 months apart
measure: Executive Function
timeFrame: 21 months - Visit 1 and Visit 2 are 21 months apart
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Washington University School of Medicine
name: Tamara A Hershey, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UPMC Children's Hospital of Pittsburgh
name: Silva Arslanian, MD
role: PRINCIPAL_INVESTIGATOR
References: