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Type 2 Diabetes MellitusPhase 1/2Renal-HEIRNCT03584217

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

A Phase 1/2 study testing Aminohippurate Sodium Inj 20%, Iohexol Inj 300 MG/ML and Renal Biopsy in people with Type 2 Diabetes Mellitus and Obesity, run by University of Colorado, Denver at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 to 21 yearsHealthy volunteers can take part
Conditions the study is for
Type 2 Diabetes Mellitus, Obesity, Nephropathy
What is being tested?
Aminohippurate Sodium Inj 20%, Iohexol Inj 300 MG/ML and Renal Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteUnited States
Study dates
1 Oct 2018to 30 Oct 2023
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 21 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 24Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Hospital Colorado

    Aurora, Colorado, 80238

Other trials in United States

About this study

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.

Being tested
Aminohippurate Sodium Inj 20%, Iohexol Inj 300 MG/ML, Renal Biopsy
Medical subject headings
Diabetes Mellitus, Type 2, Obesity, Kidney Diseases, Pediatric Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aminohippurate Sodium Inj 20%Drug

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

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

  • Iohexol Inj 300 MG/MLDrug

    Also called omnipaque 300

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

  • Renal BiopsyProcedure or surgery

    Also called Kidney Biopsy

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

Study groups in NCT03584217
Study groupRoleWhat they receive
Clinical InvestigationOtherAll participants will undergo GFR (Iohexol Inj 300 MG/ML), ERPF (Aminohippurate Sodium Inj 20%) in addition to renal BOLD and ASL MRI.
Receives: Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 MG/ML; Procedure: Renal Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Effective renal plasma flow (ERPF)

    Measured by PAH clearance

    Measured: 4 hours

  2. Glomerular filtration rate (GFR)

    Measured by iohexol clearance

    Measured: 4 hours

Secondary outcomes (3)

  1. Insulin sensitivity

    Measured by hyperinsulinemic-euglycemic clamp

    Measured: 4 hours

  2. Renal oxygenation

    Blood oxygen level dependent (BOLD) MRI

    Measured: 60 min

  3. Renal perfusion

    Arterial spin labeling (ASL) MRI

    Measured: 10 min

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2018
  2. Study start1 Oct 2018
  3. Primary completion30 Jun 2023
  4. Study completion30 Oct 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03584217
Sponsor's protocol ID
16-1752
Acronym
Renal-HEIR
Status last verified
Aug 2023
First submitted
28 Jun 2018
Last updated
15 Aug 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Vigers T, Vinovskis C, Li LP, Prasad P, Heerspink H, D'Alessandro A, Reisz JA, Piani F, Cherney DZ, van Raalte DH, Nadeau KJ, Pavkov ME, Nelson RG, Pyle L, Bjornstad P. Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes. Pediatr Nephrol. 2023 Jan;38(1):193-202. doi: 10.1007/s00467-022-05531-3. Epub 2022 May 4.

    PubMed 35507146

  • Vinovskis C, Li LP, Prasad P, Tommerdahl K, Pyle L, Nelson RG, Pavkov ME, van Raalte D, Rewers M, Pragnell M, Mahmud FH, Cherney DZ, Johnson RJ, Nadeau KJ, Bjornstad P. Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes. Diabetes. 2020 Dec;69(12):2700-2708. doi: 10.2337/db20-0457. Epub 2020 Jul 31.

    PubMed 32737116

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aminohippurate Sodium Inj 20%, Iohexol Inj 300 MG/ML and Renal Biopsy in people with Type 2 Diabetes Mellitus and Obesity, run by University of Colorado, Denver at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effective renal plasma flow (ERPF) (time frame: 4 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03584217, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2023.

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