Clinical trial NCT03960333: Immunometabolism in Pediatric Obesity
Official title: Immunometabolism in Pediatric Obesity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Type 2 Diabetes Mellitus
Insulin Resistance
Keywords: Obesity
Type2 Diabetes Mellitus
Type2 Diabetes
Insulin Resistance
Metformin
Pediatric Health
Lead sponsor: Arkansas Children's Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of General Medical Sciences (NIGMS)
name: University of Arkansas
First posted: 2019-05-23
Enrollment: 82
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 110 children ages 5-17 years old will be recruited with the goal that approximately 80 subjects stratified across the following groups will complete the study: i) healthy lean (approximately n=20); ii) overweight/obese (approximately n=40, with the anticipation that approximately 20 of these children will be insulin resistant); iii) overweight/obese with T2D and prescribed Metformin (approximately n=20). Every attempt will be made to ensure that the desired number for each group is achieved and groups are balanced with respect to age, sex and ethnicity.

Brief summary: This is a study to learn about obesity and how insulin resistance and Type 2 Diabetes develops in children.

Detailed description: The main purpose of this proposed study is to determine whether the immunometabolic phenotypes of CD4+T cells from obese children is skewed towards Teff with mTOR-driven glycolysis and away from Tregs with AMPK-driven OXPHOS and whether metformin can reverse the immunometabolic phenotypes.

This study consists of:

1. An observational cross sectional immune and metabolic analysis of several groups of children including lean, overweight/obese, and T2D.
2. A prospective immune and metabolic analysis of newly diagnosed children with T2D or insulin resistance who will be or were recently prescribed metformin as part of their clinical care.

Children with T2D or insulin resistance who will be or were recently prescribed metformin, will be asked to complete two study visits. If completed, the second visit will occur 6 months (+/- 2 weeks) after beginning metformin as part of their clinical care. All other children, will be asked to complete only the first visit.

Eligibility criteria: Inclusion Criteria:

* Age 5-17 years, inclusive
* Either healthy lean (BMI≥ 5th percentile and \<85th percentile for age/sex) or overweight (BMI ≥ 85th percentile and \<95th) or obese (BMI ≥ 95th percentile for age/sex)
* For those with BMI≥ 85th percentile for age/sex, parental verbal confirmation that the child had a history of BMI≥ 85th percentile for age/sex for at least six months prior to study enrollment OR
* Age 5 years - 17 years 5 months, inclusive
* Either overweight or obese (BMI≥ 85th percentile for age/sex)
* Parental verbal confirmation that the child had a history of BMI≥ 85th percentile for age/sex for at least six months prior to study enrollment
* Diagnosed with type 2 diabetes mellitus or insulin resistance
* Prescribed metformin (either not yet taking or began taking within 3 weeks of enrollment)

Exclusion Criteria:

* Having an infection (viral, respiratory, gastrointestinal) in the previous 4 weeks
* Genetic or physical conditions impacting mobility over past year as determined by the PI
* Having known chronic illnesses/disorders that may independently affect study outcome measures: type 1 diabetes mellitus, neurologic (e.g. epilepsy), developmental (developmental delay, autism spectrum disorder), endocrine (thyroid, Cushing's), hepatic, autoimmune, cardiac and renal disorders. Also, chronic lung disorders except well controlled asthma that does not require permanent use of inhaled/oral steroids
* Taking any of the following medications that can affect study outcome: antipsychotics, thyroid hormone replacement therapy, inhaled/oral steroids, insulin, anabolic drugs (growth hormone replacement therapy and oxandrolone) and stimulants
* Taking metformin prescribed as part of their clinical care for longer than 3 weeks at the time of enrollment (may begin metformin therapy prescribed as part of their clinical care while enrolled in the study)
* BMI\<5th percentile for age/sex (classified as underweight based on CDC growth charts)
* Subjects determined ineligible by the PI or delegated staff.

Primary outcomes:
measure: circulating CD4+T cells in Overweight/Obese vs Lean
timeFrame: After completion of all study visits, approximately 2 years.
measure: circulating CD4+T cells in Type 2 Diabetic pre/post Metformin
timeFrame: After completion of all study visits, approximately 2 years.
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Research Institute
state: Arkansas
Study officials:
affiliation: Arkansas Children's Research Institute
name: Shannon Rose, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rose S, Landes RD, Vyas KK, Delhey L, Blossom S. Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity. Immunometabolism (Cobham). 2024 Apr 25;6(2):e00040. doi: 10.1097/IN9.0000000000000040. eCollection 2024 Apr.