Renal HEIR Study: Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes Study

Renal HEIR Study: Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes Study

Sponsors

Lead Sponsor: University of Colorado Denver School of Medicine Barbara Davis Center

Source University of Colorado Denver School of Medicine Barbara Davis Center
Brief Summary

Type 2 diabetes (T2D) in youth is increasing in prevalence in parallel with the obesity epidemic. In the US, almost half of patients with renal failure have DKD, and ≥80% have T2D. Compared to adult-onset T2D, youth with T2D have a more aggressive phenotype with greater insulin resistance (IR), more rapid β-cell decline and higher prevalence of diabetic kidney disease (DKD), arguing for separate and dedicated studies in youth-onset T2D. Hyperfiltration is common in youth with T2D, and predicts progressive DKD. Hyperfiltration may also be associated with early changes in intrarenal hemodynamic function, including increased renal plasma flow (RPF) and glomerular pressure. Despite the high prevalence and gravity of DKD in youth-onset T2D, widely effective therapeutic options are lacking. The investigators' preliminary data support a strong association between IR and hyperfiltration in youth-onset T2D, but the pathology contributing to this relationship remains unclear. A better understanding of the pathophysiology underlying hyperfiltration and its relationship with IR is critical to inform development of new therapeutics. The investigators' overarching hypotheses are that: 1) hyperfiltration in youth-onset T2D is associated with changes in intrarenal hemodynamics, resulting in increased renal oxygen demand, 2) the demand is unmet by the inefficient fuel profile associated with IR (decreased glucose oxidation and increase free fatty acid [FFA] oxidation), resulting in renal hypoxia and ultimately renal damage. To address these hypotheses, the investigators will measure peripheral insulin sensitivity, adipose insulin sensitivity (FFA suppression), glomerular filtration rate (GFR), RPF, and renal oxygenation in youth with T2D (n=60), obesity (n=20) and in lean (n=20) controls. To further investigate the mechanisms of renal damage in youth with T2D, two optional procedures are included in the study: 1) kidney biopsy procedure and 2) induction of induced pluripotent stem cells (iPSCs) to assess morphometrics and genetic expression of renal tissue.

Overall Status Recruiting
Start Date October 1, 2018
Completion Date June 2023
Primary Completion Date June 2023
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Effective renal plasma flow (ERPF) 4 hours
Glomerular filtration rate (GFR) 4 hours
Secondary Outcome
Measure Time Frame
Insulin sensitivity 4 hours
Renal oxygenation 60 min
Renal perfusion 10 min
Enrollment 100
Condition
Intervention

Intervention Type: Drug

Intervention Name: Aminohippurate Sodium Inj 20%

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

Arm Group Label: Clinical Investigation

Intervention Type: Drug

Intervention Name: Iohexol Inj 300 MG/ML

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

Arm Group Label: Clinical Investigation

Other Name: omnipaque 300

Intervention Type: Procedure

Intervention Name: Renal Biopsy

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

Arm Group Label: Clinical Investigation

Other Name: Kidney Biopsy

Eligibility

Criteria:

Inclusion Criteria:

- Obese youth with and without T2D (≥54 kg) and lean controls

- Age 12-21 years

- Weight <300 lbs., no implanted metal devices

- HbA1c < 11% and no recent diabetic ketoacidosis or hyperosmolar hyperglycemia

- No anemia

- BMI >5th percentile for lean controls

Exclusion Criteria:

- T2D onset (diagnosis) > 18 years of age

- Prepubertal

- eGFR <60ml/min/1.73m2 or creatinine > 1.5mg/dl or history of ACR≥300mg/g

- ACE inhibitors, angiotensin receptor blockers (ARB), diuretics, sodium-glucose co-transport (SGLT) 2 or 1 blockers, daily NSAIDs or aspirin, sulfonamides, procaine, thiazosulfone or probenecid.

- Seafood or iodine allergy

- Pregnancy

- MRI scanning contraindications (claustrophobia, implantable devices, >300 lbs)

Additional exclusion criteria for participants undergoing optional kidney biopsy:

- Evidence of bleeding disorder or complications from bleeding

- Use of aspirin, NSAIDS or other blood thinner that cannot be safely stopped for a sufficient time period before and after the biopsy so as to add no additional risk of bleeding

- Blood urea nitrogen (BUN) > 80 gm/dL

- INR > 1.4

- PTT > 35 seconds

- Hemoglobin (Hgb) < 10 mg/dL

- Platelet count < 100,000 / µL

- Uncontrolled or difficult to control hypertension (> 150/90 mmHg at the day of biopsy)

- eGFR < 40 mL/min/1.73m2

- Single kidney (either by history, documented by prior imaging or ultrasound performed prior to the biopsy)

- > 2 cm discrepancy between left and right kidney sizes based on largest longitudinal diameter determined by ultrasound performed prior to the biopsy.

- Kidney size: One or both kidneys < 9 cm

- Hydronephrosis or other important renal ultrasound findings such as significant stone disease

- Any evidence of a current urinary tract infection as indicated on day of biopsy

- Clinical evidence of non-diabetic renal disease

- Positive urine pregnancy test or pregnancy

Gender: All

Minimum Age: 12 Years

Maximum Age: 21 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Petter Bjornstad, MD Principal Investigator University of Colorado School of Medicine
Overall Contact

Last Name: Susan Gross, MS, RD

Phone: 7207776143

Email: [email protected]

Location
Facility: Status: Contact: Investigator: Children's Hospital Colorado Petter Bjornstad, M.D. Petter Bjornstad, M.D. Principal Investigator Kristen Nadeau, M.D. Sub-Investigator
Location Countries

United States

Verification Date

May 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Colorado, Denver

Investigator Full Name: Petter Bjornstad

Investigator Title: Assistant Professor

Condition Browse
Number Of Arms 1
Arm Group

Label: Clinical Investigation

Type: Other

Description: All participants will undergo GFR (Iohexol Inj 300 MG/ML), ERPF (Aminohippurate Sodium Inj 20%) in addition to renal BOLD and ASL MRI.

Acronym Renal-HEIR
Patient Data Undecided
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Diagnostic

Masking: None (Open Label)

Source: ClinicalTrials.gov