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

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

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.

Study Overview

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

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 26 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Population to be enrolled will be comprised of obese youth with and without T2D and lean controls who were previously enrolled in the Renal-HEIR (#16-1752) study.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lean Controls (previously enrolled in the Renal HEIR Study)	Drug: Aminohippurate Sodium Inj 20%; Diagnostic aid/agent used to measure effective renal plasma flow (ERPF); Other Names: Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL; Para-aminohippurate; Aminohippuric acid; Drug: Iohexol Inj 300 MG/ML; Diagnostic aid/agent used to measure glomerular filtration rate (GFR); Other Names: omnipaque 300; Drug: Dextran 40; Diagnostic aid/agent used to measure glomerular size selectivity; Other Names: Dextran; LMD
Obese Youth without Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Drug: Aminohippurate Sodium Inj 20%; Diagnostic aid/agent used to measure effective renal plasma flow (ERPF); Other Names: Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL; Para-aminohippurate; Aminohippuric acid; Drug: Iohexol Inj 300 MG/ML; Diagnostic aid/agent used to measure glomerular filtration rate (GFR); Other Names: omnipaque 300; Drug: Dextran 40; Diagnostic aid/agent used to measure glomerular size selectivity; Other Names: Dextran; LMD; Radiation: Positron Emission Tomography; Imaging study performed to study renal oxidative metabolism; Other Names: PET Scan
Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study)	Drug: Aminohippurate Sodium Inj 20%; Diagnostic aid/agent used to measure effective renal plasma flow (ERPF); Other Names: Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL; Para-aminohippurate; Aminohippuric acid; Drug: Iohexol Inj 300 MG/ML; Diagnostic aid/agent used to measure glomerular filtration rate (GFR); Other Names: omnipaque 300; Procedure: Renal Biopsy; Minimally invasive outpatient procedure in interventional radiology to obtain renal tissue cores.; Other Names: Kidney Biopsy; Drug: Dextran 40; Diagnostic aid/agent used to measure glomerular size selectivity; Other Names: Dextran; LMD; Radiation: Positron Emission Tomography; Imaging study performed to study renal oxidative metabolism; Other Names: PET Scan

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Petter Bjornstad, MD, Children's Hospital Colorado

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Anticipated): September 1, 2027
• Study Completion (Anticipated): May 1, 2029

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 2, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Obesity; Pediatric Obesity; Diabetic Nephropathies; Insulin Resistance; Anticoagulants; Plasma Substitutes; Blood Substitutes; Dextrans
• Other Study ID Numbers: 20-2961

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No