Children's Hospital Colorado
Aurora, Colorado, 80045, United States
NCT Number: NCT04074668
Type 1 diabetes (T1D) is a complex metabolic disorder with many pathophysiological disturbances including insulin resistance (IR) and mitochondrial dysfunction which are causally related to the development of diabetic kidney disease (DKD) and which contribute to reduced life expectancy. Renal hypoxia, stemming from a potential metabolic mismatch between increased renal energy expenditure and impaired substrate utilization, is increasingly proposed as a unifying early pathway in the development of DKD. By examining the interplay between factors responsible for increased renal adenosine triphosphate (ATP) consumption and decreased ATP generation in young adults with and without T1D, this study hopes to identify novel therapeutic targets to impede the development of DKD in future trials.
The investigators propose to address the specific aims in a cross-sectional study with 30 adults with T1D and 20 controls without a diagnosis of diabetes. For this protocol, participants will complete a one day study visit at Children's Hospital Colorado. Patients will undergo a Dual-energy X-Ray Absorptiometry (DXA) scan to assess body composition, renal Magnetic Resonance Imaging (MRI) to quantify renal oxygenation and perfusion, and a Positron Emission Tomography/Computed Tomography (PET/CT) scan to quantify renal O2 consumption. After the PET and MRI, participants will undergo a hyperinsulinemic-euglycemic clamp to quantify insulin sensitivity. Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) will be measured by iohexol and PAH clearances during the hyperinsulinemic-euglycemic clamp. To further investigate the mechanisms of renal damage in T1D, 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.
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Notify Me18 year–30 year
All sexes
Observational
Aurora, Colorado, 80045, United States
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
-- Type 1 Diabetes:
Exclusion criteria
-- Type 1 Diabetes:
Inclusion criteria
-- Healthy Controls:
Exclusion criteria
-- Healthy Controls:
Additional exclusion criteria for participants undergoing optional kidney biopsy:
Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)
Other names: Sodium 4-amino hippurate (PAH) inj 20% 2 grams (g)/10 milliliters (mL), Para-aminohippurate, Aminohippuric acid
Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
Other names: omnipaque 300
Imaging used to visualize the kidneys and quantify renal metabolic activity
Minimally invasive outpatient procedure to obtain renal tissue after ultrasound visualization.
Time frame: 30 minutes
Blood oxygen level dependent (BOLD) MRI
Time frame: 30 minutes
Arterial Spin Labeling (ASL) MRI
Time frame: 30 minutes
11-C Acetate PET/CT
Time frame: 4.5 hours
Hyperinsulinemic-Euglycemic Clamp
Time frame: 5 minutes
Blood draw for mitochondrial DNA copy number
Time frame: 5 minutes
Blood draw for untargeted metabolite assessment of the tricyclic acid (TCA) cycle
Time frame: 5 minutes
Blood draw for targeted assessment and quantification of glucose oxidation using an established metabolite panel
Time frame: 5 minutes
Blood draw for untargeted metabolite assessment of Free Fatty Acid (FFA) oxidation
Time frame: 3 hours
Iohexol Clearance Study
Time frame: 2.5 hours
PAH Clearance Study
Time frame: 5 minutes
Blood draw for Plasma Renin levels
Time frame: 5 minutes
Blood draw for Angiotensin II levels
Time frame: 5 minutes
Blood draw for Copeptin levels
Time frame: 5 minutes
Blood draw for Tyrosine Lysine Leucine-40 (YKL-40) levels
Time frame: 5 minutes
Blood draw for Neutrophil gelatinase-associated lipocalin (NGAL) levels
Time frame: 5 minutes
Blood draw for Kidney Injury Marker 1 (KIM-1) levels
Time frame: 5 minutes
Blood draw for Interleukin-18 (IL-18) levels
Time frame: 5 minutes
Blood draw for Tumor Necrosis Factor Receptor 1/2 (TNF-R 1/2) levels
Time frame: 4 hours
Measured by light microscopy from tissue obtained by renal biopsy
Time frame: 4 hours
Measured by electron microscopy from tissue obtained by renal biopsy
Time frame: 4 hours
Measured by electron microscopy from tissue obtained by renal biopsy
Time frame: 4 hours
Measured by electron microscopy from tissue obtained by renal biopsy
Time frame: 4 hours
Measured from tissue obtained by renal biopsy
Time frame: 4 hours
Measured from tissue obtained by renal biopsy
University of Colorado, Denver
Other
CROCODILE Study: Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance
Acronym: CROCODILE
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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