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

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 26 years
• All sexes
• Child, Adult

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.

Trial locations and contacts

1 site in 1 country.

About this study

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

Conditions

Type 2 Diabetes, Diabetes Type 2, Diabetic Nephropathies, Nephropathy, Obesity, Adolescent Obesity

Being tested

Aminohippurate Sodium Inj 20%, Iohexol Inj 300 MG/ML, Dextran 40, Renal Biopsy, Positron Emission Tomography

Medical subject headings

Diabetes Mellitus, Type 2, Diabetic Nephropathies, Kidney Diseases, Obesity, 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)

• Dextran 40Drug

  Also called Dextran, LMD

  Diagnostic aid/agent used to measure glomerular size selectivity

• Renal BiopsyProcedure or surgery

  Also called Kidney Biopsy

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

• Positron Emission TomographyRadiation

  Also called PET Scan

  Imaging study performed to study renal oxidative metabolism

What is being measured

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

1. Glomerular Filtration Rate

   Glomerular filtration rate measured by iohexol clearance

   Measured: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

2. Effective Renal Plasma Flow (ERPF)

   Effective renal plasma flow measured by PAH clearance

   Measured: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

3. Renal Oxygen Availability

   BOLD-MRI uses the specific paramagnetic properties of deoxyhemoglobin to assess renal tissue oxygenation. Its outcome measure is the so-called R2* value, which varies inversely with local oxygenation. This apparent relaxation rate R2* (or decay rate, defined as 1/T2* and expressed as per second) is measured voxel by voxel in each kidney by BOLD-MRI. The R2* value of each voxel is influenced by microscopic inhomogeneities in the static magnetic field, largely due to the effect of deoxyhemoglobin. As such, the decay rate R2* in a voxel will be enhanced when the local deoxyhemoglobin concentration is increased. Hence, assuming that blood pO2 is in equilibrium with tissue pO2, low R2* values indicate high tissue oxygenation, while high R2* values indicate low tissue oxygenation.

   Measured: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

4. Renal Perfusion

   Arterial spin labeling (ASL) uses magnetically labeled arterial blood water as an endogenous tracer to assess renal perfusion. Its outcome measure is renal blood flow (RBF), expressed in mL/min/100 g of tissue. In ASL, inflowing arterial blood is magnetically tagged by inverting the longitudinal magnetization of water protons proximal to the imaging plane. After a defined post-labeling delay allowing labeled blood to flow into the tissue, a labeled image is acquired and subtracted from a control image obtained without labeling. The resulting difference signal, measured voxel by voxel in each kidney, is proportional to the labeled blood water delivered during the delay. As such, the difference signal in a voxel will be enhanced when local blood delivery is increased. Hence, after quantification using tissue and blood relaxation parameters, high perfusion values indicate high renal blood flow, while low perfusion values indicate reduced renal blood flow.

   Measured: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

5. C-11 Acetate Tracer Uptake

   C-11 Acetate tracer uptake measured by PET Scan (K1)

   Measured: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

6. Renal Oxidative Metabolism

   Positron emission tomography (PET) with C-11 acetate is used to assess renal oxidative metabolism. Its outcome measure is the cortical clearance rate constant k2, expressed per minute (min^-1). Following intravenous injection, C-11 acetate is taken up by renal tissue and converted to acetyl-CoA, which enters the tricarboxylic acid (TCA) cycle and is oxidized to C-11 CO2. The washout of C-11 activity from the tissue, modeled region by region in the renal cortex, reflects the rate of this oxidative process. The clearance rate constant k2, derived from kinetic modeling of the tissue time-activity curve, will be enhanced when oxidative metabolism and TCA cycle flux are increased. Hence, assuming tracer washout is in proportion to mitochondrial oxidation, high cortical k2 values indicate high renal oxidative metabolism, while low cortical k2 values indicate reduced renal oxidative metabolism.

   Measured: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

Timeline

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

1. First posted7 Sep 2022
2. Study start30 Sep 2022
3. Primary completion19 Jun 2024
4. Study completion19 Jun 2024

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
• More trials run by University of Colorado, DenverThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

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