NCT03584217: Renal-HEIR

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

Status unknown Phase 1, PHASE2 Last updated 15 August 2023

What this trial tests

Phase 1, PHASE2 trial testing Aminohippurate Sodium Inj 20% in Type 2 Diabetes Mellitus in 100 participants. Status unknown.

Timeline

1 October 2018

Primary endpoint
30 June 2023

30 October 2023

Quick facts

Lead sponsor	University of Colorado, Denver
Phase	Phase 1, PHASE2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	100
Start date	1 October 2018
Primary completion	30 June 2023
Estimated completion	30 October 2023
Sites	1 location across United States

Drugs / interventions tested

• Aminohippurate Sodium Inj 20% — full drug profile →
• Iohexol Inj 300 MG/ML — full drug profile →
• Renal Biopsy

Conditions studied

• Type 2 Diabetes Mellitus — all drugs for Type 2 Diabetes Mellitus →
• Obesity — all drugs for Obesity →
• Nephropathy — all drugs for Nephropathy →
• Adolescent Obesity — all drugs for Adolescent Obesity →

Sponsor

University of Colorado, Denver

Who can join

Adults 12 to 21, any sex, with Type 2 Diabetes Mellitus or Obesity. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. SGLT2 inhibitors mitigate kidney tubular metabolic and mTORC1 perturbations in youth-onset type 2 diabetes.
   Schaub JA, AlAkwaa FM, McCown PJ, Naik AS, et al · · 2023 · cited 91× · PMID 36637914 · DOI 10.1172/jci164486
2. Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes.
   Vinovskis C, Li LP, Prasad P, Tommerdahl K, et al · · 2020 · cited 40× · PMID 32737116 · DOI 10.2337/db20-0457
3. Molecular programs associated with glomerular hyperfiltration in early diabetic kidney disease.
   Stefansson VTN, Nair V, Melsom T, Looker HC, et al · · 2022 · cited 26× · PMID 36055599 · DOI 10.1016/j.kint.2022.07.033
4. Clinical trials in-a-dish for cardiovascular medicine.
   Wu X, Swanson K, Yildirim Z, Liu W, et al · · 2024 · cited 17× · PMID 39270727 · DOI 10.1093/eurheartj/ehae519
5. Pathology-oriented multiplexing enables integrative disease mapping.
   Kuehl M, Okabayashi Y, Wong MN, Gernhold L, et al · · 2025 · cited 11× · PMID 40681898 · DOI 10.1038/s41586-025-09225-2
6. Relationship between biomarkers of tubular injury and intrarenal hemodynamic dysfunction in youth with type 1 diabetes.
   Johnson MJ, Tommerdahl KL, Vinovskis C, Waikar S, et al · · 2022 · cited 9× · PMID 35286453 · DOI 10.1007/s00467-022-05487-4
7. Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes.
   Bjornstad P, Choi YJ, Platnick C, Gross S, et al · · 2024 · cited 7× · PMID 38153805 · DOI 10.2337/dc23-1818
8. Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes.
   Vigers T, Vinovskis C, Li LP, Prasad P, et al · · 2023 · cited 5× · PMID 35507146 · DOI 10.1007/s00467-022-05531-3