Immunometabolism in Pediatric Obesity (IPO)

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

Study Overview

Status

Active, not recruiting

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.

Study Type

Observational

Enrollment (Estimated)

110

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Arkansas Children's Research Institute

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

5 years to 17 years (Child)

Accepts Healthy Volunteers

N/A

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.

Description

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.

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
Healthy Lean
Healthy lean individuals (n=20) defined with a Body Mass Index (BMI) ≥ 5th percentile and <85th percentile for age/sex will be recruited. Participants in this cohort will be asked to complete a one-time study visit.
Overweight/Obese
Overweight/Obese individuals (n=20) defined with a Body Mass Index (BMI) ≥ 85th percentile for age/sex will be recruited. Participants in this cohort will be asked to complete a one-time study visit.
Type 2 Diabetes or Insulin Resistant
Obese individuals with Type 2 Diabetes or insulin resistance who have been recently prescribed Metformin and have a Body Mass Index (BMI) ≥ 85th percentile for age/sex (n=20) will be recruited. Participants in this cohort will be asked to complete a two study visits approximately 6 months apart.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
circulating CD4+T cells in Overweight/Obese vs Lean
Time Frame: After completion of all study visits, approximately 2 years.
We will measure and report the percent of ATP derived from glycolysis and oxidative phosphorylation in circulating CD4+ T cells as well as the % CD4+CD25+CD127lowFoxP3+ cells (Tregs) in overweight/obese vs lean children.
After completion of all study visits, approximately 2 years.
circulating CD4+T cells in Type 2 Diabetic pre/post Metformin
Time Frame: After completion of all study visits, approximately 2 years.
We will measure and report the percent of ATP derived from glycolysis and oxidative phosphorylation in circulating CD4+ T cells as well as the % CD4+CD25+CD127lowFoxP3+ cells (Tregs) in Type 2 Diabetic children pre and post-Metformin treatment.
After completion of all study visits, approximately 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Shannon Rose, PhD, Arkansas Children's Research Institute

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)

April 25, 2019

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

May 6, 2019

First Submitted That Met QC Criteria

May 20, 2019

First Posted (Actual)

May 23, 2019

Study Record Updates

Last Update Posted (Actual)

February 21, 2024

Last Update Submitted That Met QC Criteria

February 20, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The information collected at the study visit, urine, and stool samples, and remaining blood samples may be stored indefinitely and may be used for future research studies on pediatric nutrition or metabolism. Prior to the information collected at the study visit and samples being used for future research studies, the PI will assess the ethics and scientific merit of the proposed research with the samples, and proposed future research will be reviewed by the IRB as may be required.

IPD Sharing Time Frame

The data and samples will be available after all data has been collected for the study and all samples have been processed for the study. Prior to the information collected at the study visit and samples being used for future research studies, the PI will assess the ethics and scientific merit of the proposed research with the samples, and proposed future research will be reviewed by the Institutional Review Board (IRB) as may be required.

IPD Sharing Access Criteria

The samples and health information collected for the study visit may be shared with researchers at the University of Arkansas for Medical Sciences, Arkansas Children's Hospital, or Arkansas Children's Research Institute. The samples may be shared with an outside group. The samples will only have a study number, visit number, and study acronym to maintain confidentiality.

IPD Sharing Supporting Information Type

  • CSR

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.

Clinical Trials on Obesity

3
Subscribe