Renal Hemodynamics, Energetics and Insulin Resistance: A Follow-up Study (HEIRitage)

University of Colorado Denver (CU Denver)

Status: Invitation-only

Conditions: Nephropathy; Diabetic Nephropathies; Obesity; Type 2 Diabetes; Adolescent Obesity; Diabetes Type 2; Diabetic Kidney Disease

Treatments: Drug: Iohexol Inj 300 MG/ML; Drug: Aminohippurate Sodium Inj 20%; Radiation: Positron Emission Tomography; Drug: Dextran 40; Procedure: Renal Biopsy

Study type: Observational

Funder types: Other

Identifiers

NCT05530356

20-2961

Details and patient eligibility

About

The current protocol plans to enroll participants with youth-onset Type 2 Diabetes (T2D) as well as obese and lean controls from the Renal-HEIR - Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes Study (n=100) [COMIRB #16-1752] in a prospective investigation that seeks to 1) define the changes in kidney function by gold standard techniques and energetics by functional Magnetic Resonance Imaging (MRI) in adolescents with and without T2D as they transition to young adulthood; 2) quantify kidney oxidative metabolism by 11C-acetate Positron Emission Tomography (PET) in a subset of participants who are ≥18 years of age with youth-onset T2D and/or obesity; 3) determine peripheral arterial stiffness by SphygmoCor. Mechanistic insight will be provided by transcriptomic analyses of repeat biopsies 3-years after their initial biopsy for eligible participants with youth-onset T2D, as well as molecular analysis of tissue obtained from J-wire endovascular biopsies. This study will also leverage this well-characterized cohort of youths to define youth-onset T2D-related changes in brain morphology and function by structural MRI and resting-state functional MRI and through the assessment of cognitive function (fluid and crystallized intelligence) using the NIH Toolbox Cognitive Battery (NIHTB-CB), as an exploratory objective. All enrollees in Renal-HEIR have consented to be contacted for future research opportunities.

Enrollment: 100 estimated patients

Sex: All

Ages: 12 to 26 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Obese youth with and without Type 2 Diabetes + lean controls who were previously enrolled in the Renal HEIR Study
• Participants who will undergo a PET Scan: ≥ 18 years

Exclusion criteria

• Anemia
• Seafood, iodine, or penicillin allergy
• Pregnancy
• MRI Scanning contraindications (claustrophobia, implantable devices, >550 lbs)
• History of bleeding or clotting disorders, thrombocytopenia, warfarin and/or heparin use
• Taking sulfonamides, procaine, thiazolsulfone or probenecid

Trial design

100 participants in 3 patient groups

Lean Controls (previously enrolled in the Renal HEIR Study)

Treatment:

Drug: Dextran 40

Drug: Aminohippurate Sodium Inj 20%

Drug: Iohexol Inj 300 MG/ML

Obese Youth without Type 2 Diabetes (previously enrolled in the Renal HEIR Study)

Treatment:

Drug: Dextran 40

Radiation: Positron Emission Tomography

Drug: Aminohippurate Sodium Inj 20%

Drug: Iohexol Inj 300 MG/ML

Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study)

Treatment:

Procedure: Renal Biopsy

Drug: Dextran 40

Radiation: Positron Emission Tomography

Drug: Aminohippurate Sodium Inj 20%

Drug: Iohexol Inj 300 MG/ML