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Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance (CROCODILE)

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ClinicalTrials.gov Identifier: NCT04074668
Recruitment Status : Not yet recruiting
First Posted : August 30, 2019
Last Update Posted : August 30, 2019
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Petter Bjornstad, University of Colorado Denver School of Medicine Barbara Davis Center

Tracking Information
First Submitted Date August 6, 2019
First Posted Date August 30, 2019
Last Update Posted Date August 30, 2019
Estimated Study Start Date November 1, 2019
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 28, 2019)
  • Renal Oxygenation [ Time Frame: 30 minutes ]
    Blood oxygen level dependent (BOLD) MRI
  • Renal Perfusion [ Time Frame: 30 minutes ]
    Arterial Spin Labeling (ASL) MRI
  • Renal Oxygen Consumption [ Time Frame: 30 minutes ]
    11-C Acetate PET/CT
  • Insulin Sensitivity [ Time Frame: 4.5 hours ]
    Hyperinsulinemic-Euglycemic Clamp
  • Mitochondrial Function [ Time Frame: 5 minutes ]
    Blood draw for mitochondrial DNA copy number
  • Mitochondrial Function [ Time Frame: 5 minutes ]
    Blood draw for untargeted metabolite assessment of the tricyclic acid (TCA) cycle
  • Mitochondrial Function [ Time Frame: 5 minutes ]
    Blood draw for targeted assessment and quantification of glucose oxidation using an established metabolite panel
  • Mitochondrial Function [ Time Frame: 5 minutes ]
    Blood draw for untargeted metabolite assessment of Free Fatty Acid (FFA) oxidation
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: August 28, 2019)
  • Glomerular Filtration Rate (GFR) [ Time Frame: 3 hours ]
    Iohexol Clearance Study
  • Effective Renal Plasma Flow (ERPF) [ Time Frame: 2.5 hours ]
    PAH Clearance Study
  • Renin-Angiotensin-Aldosterone-System Activity [ Time Frame: 5 minutes ]
    Blood draw for Plasma Renin levels
  • Renin-Angiotensin-Aldosterone-System Activity [ Time Frame: 5 minutes ]
    Blood draw for Angiotensin II levels
  • Renin-Angiotensin-Aldosterone-System Activity [ Time Frame: 5 minutes ]
    Blood draw for Copeptin levels
  • Kidney Injury Biomarkers [ Time Frame: 5 minutes ]
    Blood draw for Tyrosine Lysine Leucine-40 (YKL-40) levels
  • Kidney Injury Biomarkers [ Time Frame: 5 minutes ]
    Blood draw for Neutrophil gelatinase-associated lipocalin (NGAL) levels
  • Kidney Injury Biomarkers [ Time Frame: 5 minutes ]
    Blood draw for Kidney Injury Marker 1 (KIM-1) levels
  • Kidney Injury Biomarkers [ Time Frame: 5 minutes ]
    Blood draw for Interleukin-18 (IL-18) levels
  • Kidney Injury Biomarkers [ Time Frame: 5 minutes ]
    Blood draw for Tumor Necrosis Factor Receptor 1/2 (TNF-R 1/2) levels
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance
Official Title CROCODILE Study: Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance
Brief Summary

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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
During the study, blood and urine samples will be collected for assessment of kidney function and kidney injury markers.
Sampling Method Probability Sample
Study Population We propose to address the specific aims of this study in a cross-sectional project with 30 adults with T1D and 20 controls (50% female, ages 18-30 yr).
Condition
  • Diabetic Kidney Disease
  • Type 1 Diabetes
  • Diabetes
  • Diabetes Mellitus
  • Diabetes Complications
  • Diabetic Nephropathies
  • Type1diabetes
  • Diabetes, Autoimmune
  • Autoimmune Diabetes
  • Juvenile Diabetes
  • Type 1 Diabetes Mellitus
Intervention
  • Drug: Aminohippurate Sodium Inj 20%
    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
  • Drug: Iohexol Inj 300 milligrams/milliliter (mg/ml)
    Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
    Other Name: omnipaque 300
  • Radiation: PET/CT Scan
    Imaging used to visualize the kidneys and quantify renal metabolic activity
Study Groups/Cohorts
  • Type 1 Diabetes
    All participants will undergo DXA scan, magnetic resonance imaging (MRI) studies of the kidneys, PET/CT using 11-C acetate to measure renal oxygen consumption, hyperinsulinemic-euglycemic clamp to quantify insulin sensitivity, and renal clearance testing using iohexol and para-aminohippurate (PAH) to quantify glomerular filtration rate (GFR) and effective renal plasma flow (ERPF).
    Interventions:
    • Drug: Aminohippurate Sodium Inj 20%
    • Drug: Iohexol Inj 300 milligrams/milliliter (mg/ml)
    • Radiation: PET/CT Scan
  • Healthy Controls
    All participants will undergo DXA scan, magnetic resonance imaging (MRI) studies of the kidneys, PET/CT using 11-C acetate to measure renal oxygen consumption, hyperinsulinemic-euglycemic clamp to quantify insulin sensitivity, and renal clearance testing using iohexol and para-aminohippurate (PAH) to quantify glomerular filtration rate (GFR) and effective renal plasma flow (ERPF).
    Interventions:
    • Drug: Aminohippurate Sodium Inj 20%
    • Drug: Iohexol Inj 300 milligrams/milliliter (mg/ml)
    • Radiation: PET/CT Scan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: August 28, 2019)
50
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 31, 2022
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria -- Type 1 Diabetes:

  • Antibody positive Type 1 Diabetes with duration > 5 years
  • BMI between 18.5 and 30 kg/m2
  • Weight < 350 lbs
  • HbA1c < 11%
  • Hemoglobin >= 12 g/dl

Exclusion Criteria -- Type 1 Diabetes:

  • Recent diagnosis (within 3 months) of Diabetic Ketoacidosis (DKA)
  • Severe illness
  • Pregnancy, nursing
  • Anemia
  • Allergy to shellfish or iodine
  • Claustrophobia or implantable metal devices (MRI contraindications)
  • High blood pressure (greater than 130/80 mm Hg)
  • Elevated Urine Albumin-to-Creatinine Ratio (UACR) (>30 mg/g) or estimated Glomerular Filtration Rate (eGFR) <90 ml/min/1.73 m2
  • Taking ACE inhibitors (ACEis), Angiotensin receptor blockers (ARBs), diuretics, Sodium Glucose Transporter (SGLT) 1/2 blockers

Inclusion Criteria -- Healthy Controls:

  • No diagnosis of Type 1 or Type 2 Diabetes
  • BMI between 18.5 and 30 kg/m2
  • Weight < 350 lbs
  • HbA1c < 11%
  • Hemoglobin >= 12 g/dl

Exclusion Criteria -- Healthy Controls:

  • Severe illness
  • Pregnancy, nursing
  • Anemia
  • Allergy to shellfish or iodine
  • Claustrophobia or implantable metal devices (MRI contraindications)
  • High blood pressure (greater than 130/80 mm Hg)
  • Elevated UACR (>30 mg/g) or eGFR <90 ml/min/1.73 m2
  • Taking ACE inhibitors (ACEis), Angiotensin receptor blockers (ARBs), diuretics, SGLT 1/2 blockers
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 30 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Carissa Vinovskis, MS 720-777-2660 carissa.vinovskis@childrenscolorado.org
Contact: Petter Bjornstad, MD 720-777-4659 petter.bjornstad@childrenscolorado.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04074668
Other Study ID Numbers 19-1282
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Petter Bjornstad, University of Colorado Denver School of Medicine Barbara Davis Center
Study Sponsor University of Colorado Denver School of Medicine Barbara Davis Center
Collaborators Juvenile Diabetes Research Foundation
Investigators Not Provided
PRS Account University of Colorado Denver School of Medicine Barbara Davis Center
Verification Date August 2019