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

• Conditions: Type 2 Diabetes; Diabetic Nephropathies; Adolescent Obesity; Diabetic Kidney Disease; Nephropathy; Obesity; Diabetes Type 2
• Interventions: Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 MG/ML; Drug: Dextran 40; Procedure: Renal Biopsy; Radiation: Positron Emission Tomography

• Registration Number: NCT05530356
• Lead Sponsor: University of Colorado, Denver

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-02
• Study First Submitted QC: 2022-09-02
• Study First Posted: 2022-09-07
• Study Start: 2022-09-30
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-31
• Last Update Posted: 2022-11-02
• Primary Completion: 2027-09
• Study Completion: 2029-05

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 100

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Obese Youth without Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Aminohippurate Sodium Inj 20%	-
Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Iohexol Inj 300 MG/ML	-
Obese Youth without Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Dextran 40	-
Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Dextran 40	-
Lean Controls (previously enrolled in the Renal HEIR Study)	Iohexol Inj 300 MG/ML	-
Obese Youth without Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Iohexol Inj 300 MG/ML	-
Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Aminohippurate Sodium Inj 20%	-
Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Positron Emission Tomography	-
Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Renal Biopsy	-
Lean Controls (previously enrolled in the Renal HEIR Study)	Dextran 40	-
Lean Controls (previously enrolled in the Renal HEIR Study)	Aminohippurate Sodium Inj 20%	-
Obese Youth without Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Positron Emission Tomography	-

Primary Outcome Measures

Name	Time	Method
Glomerular Filtration Rate	4 Hours	Measured by Iohexol Clearance
Interstitial Fibrosis	1 Hour	Measured by Renal Biopsy
Renal Arteriosclerosis	1 Hour	Measured by Renal Biopsy
Spatial Metabolomics	1 Hour	Measured by Renal Biopsy
Glomerular Size Selectivity	4 hours	Measured by Dextran sieving
Blood Volume Fraction	1 Hour	Measured by PET Scan
Effective Renal Plasma Flow (ERPF)	4 Hours	Measured by PAH clearance
Renal Oxygen Availability	1 hour	Measured by functional kidney MRI
11-C Acetate Tracer Uptake	1 Hour	Measured by PET Scan
Glomerular Basement Membrane Width	1 Hour	Measured by Renal Biopsy
Mesangial Expansion	1 Hour	Measured by Renal Biopsy
Renal Perfusion	1 hour	Measured by functional kidney MRI + PET Scan
Renal Oxidative Metabolism	1 Hour	Measured by PET Scan
Spatial Transcriptomics	1 Hour	Measured by Renal Biopsy

Secondary Outcome Measures

Name	Time	Method
Whole brain gray matter volume	1 Hour	Measured by brain MRI
Whole brain cortical thickness	1 Hour	Measured by brain MRI
Whole brain resting-state network connectivity	1 Hour	Measured by brain MRI
Age-corrected composite fluid cognition score	1 Hour	Measured by brain MRI
Pulse Wave Velocity between Carotid and Femoral Artery	10 minutes	Measured by PWV

Trial Locations

Locations (1)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States