Clinical trial NCT06525259: DISCOVERY of Risk Factors for Type 2 Diabetes in Youth
Official title: DISCOVERY of Risk Factors for Type 2 Diabetes in Youth
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diabetes Mellitus Type 2, Childhood-Onset
Lead sponsor: George Washington University
Sponsor class: OTHER
First posted: 2024-07-29
Enrollment: 3600
Sex: ALL
Minimum age (years): 9
Maximum age (years): 14
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 3,600 youth, aged 9-14 years at enrollment, of all genders and race/ethnic groups from 15 clinical centers in the United States will be included. Youth will be overweight or obese (BMI ≥85th percentile for age) and have evidence of dysglycemia with an HbA1c range from 5.5-6.4% at screening.

Brief summary: The goal of the DISCOVERY study is to provide innovative critical information regarding the unique natural history of glycemic control, insulin sensitivity, and β-cell function, and their mechanistic determinates, in obese adolescents at risk for developing type 2 diabetes.

Detailed description: The DISCOVERY study will extensively phenotype a large cohort of youth at-risk for type 2 diabetes, as they transition through puberty, and characterize the course of dysfunction in pathophysiological indicators that lead to type 2 diabetes. The knowledge gained from this study of the pathophysiology and epidemiology of youth-onset type 2 diabetes with deep biochemical, clinical, and psychosocial phenotyping will critically inform the design and testing of future treatment and prevention approaches.

Eligibility criteria: Inclusion Criteria:

Screening will occur to enrich the yield of individuals who are highly predisposed to develop youth-onset type 2 diabetes and include those with all of the criteria in Category A:

* Overweight or obesity with BMI ≥85th percentile
* Age 9-13 year for girls, 10-14 year for boys (inclusion younger for girls as puberty tends to start a year earlier in girls)
* Tanner Stage 2, 3, or 4
* Elevated HbA1c 5.5-6.4%

Participants who meet all of these categories will further need to meet at least one criterion in Category B:

* Family history of type 2 diabetes in 1st or 2nd degree relative
* Personal exposure to maternal diabetes (i.e., gestational diabetes mellitus (GDM) or mother with type 1 or type 2 diabetes while pregnant with participant)
* HbA1c ≥6.0%
* Severe obesity (BMI ≥99th percentile)
* Personal history of intrauterine growth restriction (IUGR), small for gestational age (SGA), or low birth weight

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation:

* Diabetes based on history, or HbA1c ≥6.5% in the medical record or at screening
* Unable/unwilling to provide consent/participate fully
* Conditions predisposing to diabetes or altering the trajectory of puberty (transplant, cancer, Down Syndrome, Turner Syndrome, Klinefelter Syndrome, ovarian/testicular failure, etc.)
* Medications affecting glucose dynamics during the screening and enrollment period (oral steroids, inhaled steroids \>1,000mcg/day past month, atypical antipsychotics, topiramate)
* Prior treatment with insulin
* Use of glucagon-like peptide-1 (GLP-1) receptor agonist or any weight loss medications in the 6 weeks prior to enrollment
* Planning treatment with glucagon-like peptide-1 (GLP-1) receptor agonist or any weight loss medications
* Use of metformin or any glucose lowering medication for a reason other than treatment of diabetes (e.g., for PCOS) in the 6 weeks prior to enrollment
* Known syndromic/monogenic obesity
* Blood disorders impacting HbA1c (e.g., anemia, hemoglobin variants)
* Major systemic organ disease
* History of bariatric surgery or currently planning bariatric surgery
* Current pregnancy or currently planning pregnancy
* Use of GnRH agonist, estrogen, or testosterone
* Individuals who do not speak English or Spanish, given validation of the questionnaires to be utilized

Primary outcomes:
measure: Type 2 diabetes
timeFrame: Through study completion, an average of 2.5 years
Secondary outcomes:
measure: Glycemia, β-cell function, insulin sensitivity, and free fatty acid flux
timeFrame: Through study completion, an average of 2.5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona State University
state: Arizona
city: Phoenix
country: United States
facility: Phoenix Children's
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: St. Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Boston Children's/Joslin Diabetes Center/Massachusetts General Hospital
state: Massachusetts
city: Shiprock
country: United States
facility: Colorado Navajo Nation
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Brooklyn
country: United States
facility: NYU Langone Health- Brooklyn
state: New York
city: Garden City
country: United States
facility: NYU Langone Health- Long Island
state: New York
city: New York
country: United States
facility: NYU Langone Health- Manhattan
state: New York
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: The University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine / Texas Children's
state: Texas
Study officials:
References: