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

NCT05530356 | Enrolling By Invitation FDA Drug

• 1 other identifier: 20-2961
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (5)

• Pulse Wave Velocity between Carotid and Femoral Artery

  10 minutes

• Whole brain gray matter volume

  1 Hour

• Whole brain cortical thickness

  1 Hour

• Whole brain resting-state network connectivity

  1 Hour

• Age-corrected composite fluid cognition score

  1 Hour

Study Arms (3)

Lean Controls (previously enrolled in the Renal HEIR Study)

Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 MG/ML; Drug: Dextran 40

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

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

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

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

Interventions

Aminohippurate Sodium Inj 20% DRUG

Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Also known as: Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL, Para-aminohippurate, Aminohippuric acid

Lean Controls (previously enrolled in the Renal HEIR Study); Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study); Obese Youth without Type 2 Diabetes (previously enrolled in the Renal HEIR Study)

Iohexol Inj 300 MG/ML DRUG

Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Also known as: omnipaque 300

Lean Controls (previously enrolled in the Renal HEIR Study); Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study); Obese Youth without Type 2 Diabetes (previously enrolled in the Renal HEIR Study)

Dextran 40 DRUG

Diagnostic aid/agent used to measure glomerular size selectivity

Also known as: Dextran, LMD

Lean Controls (previously enrolled in the Renal HEIR Study); Obese Youth with Type 2 Diabetes (previously enrolled in the Renal HEIR Study); Obese Youth without Type 2 Diabetes (previously enrolled in the Renal HEIR Study)

Renal Biopsy PROCEDURE

Minimally invasive outpatient procedure in interventional radiology to obtain renal tissue cores.

Also known as: Kidney Biopsy

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

Positron Emission Tomography RADIATION

Imaging study performed to study renal oxidative metabolism

Also known as: PET Scan

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

Eligibility Criteria

• Age: 12 Years - 26 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Samples to be retained will include urine, plasma, and serum

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetic Nephropathies; Kidney Diseases; Obesity; Pediatric Obesity

Interventions

p-Aminohippuric Acid; Iohexol; Dextrans; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminohippuric Acids; Hippurates; Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Keto Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triiodobenzoic Acids; Iodobenzoates; Glucans; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Petter Bjornstad, MD

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2022
• First Posted: September 7, 2022
• Study Start: September 30, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): May 1, 2029
• Last Updated: November 2, 2022

Record last verified: 2022-10

Locations

US (1)