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

Obesity Clinical Trial

— HEIRitage  

Official title:

Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes: A Follow-up Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05530356
• Other study ID #: 20-2961
• Status: Enrolling by invitation
• Start date: September 30, 2022
• Est. completion date: May 2029

Study information

• Verified date: October 2022
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: May 2029
• Est. primary completion date: September 2027
• Gender: All
• Age group: 12 Years to 26 Years

Eligibility

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

Related Conditions & MeSH terms

• Adolescent Obesity
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes Type 2
• Diabetic Kidney Disease
• Diabetic Nephropathies
• Insulin Resistance
• Kidney Diseases
• Nephropathy
• Obesity
• Pediatric Obesity
• Type 2 Diabetes

Intervention

Drug:
• Aminohippurate Sodium Inj 20%
Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)
• Iohexol Inj 300 MG/ML
Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
• Dextran 40
Diagnostic aid/agent used to measure glomerular size selectivity

Procedure:
• Renal Biopsy
Minimally invasive outpatient procedure in interventional radiology to obtain renal tissue cores.

Radiation:
• Positron Emission Tomography
Imaging study performed to study renal oxidative metabolism

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effective Renal Plasma Flow (ERPF)	Measured by PAH clearance	4 Hours
Primary	Glomerular Filtration Rate	Measured by Iohexol Clearance	4 Hours
Primary	Glomerular Size Selectivity	Measured by Dextran sieving	4 hours
Primary	Renal Oxygen Availability	Measured by functional kidney MRI	1 hour
Primary	Renal Perfusion	Measured by functional kidney MRI + PET Scan	1 hour
Primary	11-C Acetate Tracer Uptake	Measured by PET Scan	1 Hour
Primary	Renal Oxidative Metabolism	Measured by PET Scan	1 Hour
Primary	Blood Volume Fraction	Measured by PET Scan	1 Hour
Primary	Glomerular Basement Membrane Width	Measured by Renal Biopsy	1 Hour
Primary	Mesangial Expansion	Measured by Renal Biopsy	1 Hour
Primary	Interstitial Fibrosis	Measured by Renal Biopsy	1 Hour
Primary	Renal Arteriosclerosis	Measured by Renal Biopsy	1 Hour
Primary	Spatial Transcriptomics	Measured by Renal Biopsy	1 Hour
Primary	Spatial Metabolomics	Measured by Renal Biopsy	1 Hour
Secondary	Pulse Wave Velocity between Carotid and Femoral Artery	Measured by PWV	10 minutes
Secondary	Whole brain gray matter volume	Measured by brain MRI	1 Hour
Secondary	Whole brain cortical thickness	Measured by brain MRI	1 Hour
Secondary	Whole brain resting-state network connectivity	Measured by brain MRI	1 Hour
Secondary	Age-corrected composite fluid cognition score	Measured by brain MRI	1 Hour