Ignite Creation Date:
2025-12-24 @ 6:28 PM
Ignite Modification Date:
2026-01-06 @ 5:12 AM
Study NCT ID:
NCT04074668
Status:
COMPLETED
Last Update Posted:
2023-02-09
First Post:
2019-08-06
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003928', 'term': 'Diabetic Nephropathies'}, {'id': 'D003922', 'term': 'Diabetes Mellitus, Type 1'}, {'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D048909', 'term': 'Diabetes Complications'}], 'ancestors': [{'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D010130', 'term': 'p-Aminohippuric Acid'}, {'id': 'D007472', 'term': 'Iohexol'}], 'ancestors': [{'id': 'D000618', 'term': 'Aminohippuric Acids'}, {'id': 'D006626', 'term': 'Hippurates'}, {'id': 'D001549', 'term': 'Benzamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D062366', 'term': 'para-Aminobenzoates'}, {'id': 'D062365', 'term': 'Aminobenzoates'}, {'id': 'D001565', 'term': 'Benzoates'}, {'id': 'D000146', 'term': 'Acids, Carbocyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D007651', 'term': 'Keto Acids'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D014283', 'term': 'Triiodobenzoic Acids'}, {'id': 'D007463', 'term': 'Iodobenzoates'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'During the study, blood and urine samples will be collected for assessment of kidney function and kidney injury markers.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'CROSS_SECTIONAL', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 58}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-01-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-02', 'completionDateStruct': {'date': '2022-11-15', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-02-08', 'studyFirstSubmitDate': '2019-08-06', 'studyFirstSubmitQcDate': '2019-08-28', 'lastUpdatePostDateStruct': {'date': '2023-02-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-08-30', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-05-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Podocyte numerical density and number per glomerulus', 'timeFrame': '4 hours', 'description': 'Measured by light microscopy from tissue obtained by renal biopsy'}, {'measure': 'Foot process width of glomeruli', 'timeFrame': '4 hours', 'description': 'Measured by electron microscopy from tissue obtained by renal biopsy'}, {'measure': 'Detachment and endothelial fenestration of glomeruli', 'timeFrame': '4 hours', 'description': 'Measured by electron microscopy from tissue obtained by renal biopsy'}, {'measure': 'Podocyte volume of glomeruli', 'timeFrame': '4 hours', 'description': 'Measured by electron microscopy from tissue obtained by renal biopsy'}, {'measure': 'Number and identity of RNA in kidney cells', 'timeFrame': '4 hours', 'description': 'Measured from tissue obtained by renal biopsy'}, {'measure': 'Epigenetic profiling', 'timeFrame': '4 hours', 'description': 'Measured from tissue obtained by renal biopsy'}], 'primaryOutcomes': [{'measure': 'Renal Oxygenation', 'timeFrame': '30 minutes', 'description': 'Blood oxygen level dependent (BOLD) MRI'}, {'measure': 'Renal Perfusion', 'timeFrame': '30 minutes', 'description': 'Arterial Spin Labeling (ASL) MRI'}, {'measure': 'Renal Oxygen Consumption', 'timeFrame': '30 minutes', 'description': '11-C Acetate PET/CT'}, {'measure': 'Insulin Sensitivity', 'timeFrame': '4.5 hours', 'description': 'Hyperinsulinemic-Euglycemic Clamp'}, {'measure': 'Mitochondrial Function', 'timeFrame': '5 minutes', 'description': 'Blood draw for mitochondrial DNA copy number'}, {'measure': 'Mitochondrial Function', 'timeFrame': '5 minutes', 'description': 'Blood draw for untargeted metabolite assessment of the tricyclic acid (TCA) cycle'}, {'measure': 'Mitochondrial Function', 'timeFrame': '5 minutes', 'description': 'Blood draw for targeted assessment and quantification of glucose oxidation using an established metabolite panel'}, {'measure': 'Mitochondrial Function', 'timeFrame': '5 minutes', 'description': 'Blood draw for untargeted metabolite assessment of Free Fatty Acid (FFA) oxidation'}], 'secondaryOutcomes': [{'measure': 'Glomerular Filtration Rate (GFR)', 'timeFrame': '3 hours', 'description': 'Iohexol Clearance Study'}, {'measure': 'Effective Renal Plasma Flow (ERPF)', 'timeFrame': '2.5 hours', 'description': 'PAH Clearance Study'}, {'measure': 'Renin-Angiotensin-Aldosterone-System Activity', 'timeFrame': '5 minutes', 'description': 'Blood draw for Plasma Renin levels'}, {'measure': 'Renin-Angiotensin-Aldosterone-System Activity', 'timeFrame': '5 minutes', 'description': 'Blood draw for Angiotensin II levels'}, {'measure': 'Renin-Angiotensin-Aldosterone-System Activity', 'timeFrame': '5 minutes', 'description': 'Blood draw for Copeptin levels'}, {'measure': 'Kidney Injury Biomarkers', 'timeFrame': '5 minutes', 'description': 'Blood draw for Tyrosine Lysine Leucine-40 (YKL-40) levels'}, {'measure': 'Kidney Injury Biomarkers', 'timeFrame': '5 minutes', 'description': 'Blood draw for Neutrophil gelatinase-associated lipocalin (NGAL) levels'}, {'measure': 'Kidney Injury Biomarkers', 'timeFrame': '5 minutes', 'description': 'Blood draw for Kidney Injury Marker 1 (KIM-1) levels'}, {'measure': 'Kidney Injury Biomarkers', 'timeFrame': '5 minutes', 'description': 'Blood draw for Interleukin-18 (IL-18) levels'}, {'measure': 'Kidney Injury Biomarkers', 'timeFrame': '5 minutes', 'description': 'Blood draw for Tumor Necrosis Factor Receptor 1/2 (TNF-R 1/2) levels'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Diabetic Kidney Disease', 'Type 1 Diabetes', 'Diabetes', 'Diabetes Mellitus', 'Diabetes Complications', 'Diabetic Nephropathies', 'Type1diabetes', 'Diabetes, Autoimmune', 'Autoimmune Diabetes', 'Juvenile Diabetes', 'Type 1 Diabetes Mellitus']}, 'referencesModule': {'references': [{'pmid': '39436695', 'type': 'DERIVED', 'citation': 'Choi YJ, Richard G, Zhang G, Hodgin JB, Demeke DS, Yang Y, Schaub JA, Tamayo IM, Gurung BK, Naik AS, Nair V, Birznieks C, MacDonald A, Narongkiatikhun P, Gross S, Driscoll L, Flynn M, Tommerdahl K, Nadeau KJ, Shah VN, Vigers T, Snell-Bergeon JK, Kendrick J, van Raalte DH, Li LP, Prasad P, Ladd P, Chin BB, Cherney DZ, McCown PJ, Alakwaa F, Otto EA, Brosius FC, Saulnier PJ, Puelles VG, Goodrich JA, Street K, Venkatachalam MA, Ruiz A, de Boer IH, Nelson RG, Pyle L, Blondin DP, Sharma K, Kretzler M, Bjornstad P. Attenuated kidney oxidative metabolism in young adults with type 1 diabetes. J Clin Invest. 2024 Oct 22;134(24):e183984. doi: 10.1172/JCI183984.'}, {'pmid': '38621633', 'type': 'DERIVED', 'citation': 'Bjornstad P, Richard G, Choi YJ, Nowak KL, Steele C, Chonchol MB, Nadeau KJ, Vigers T, Pyle L, Tommerdahl K, van Raalte DH, Hilkin A, Driscoll L, Birznieks C, Hopp K, Wang W, Edelstein C, Nelson RG, Gregory AV, Kline TL, Blondin D, Gitomer B. Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study. Am J Kidney Dis. 2024 Sep;84(3):286-297.e1. doi: 10.1053/j.ajkd.2024.02.016. Epub 2024 Apr 15.'}]}, 'descriptionModule': {'briefSummary': "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.\n\nThe 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '30 Years', 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': '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).', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria -- Type 1 Diabetes:\n\n* Antibody positive Type 1 Diabetes with duration \\> 5 years\n* BMI between 18.5 and 30 kg/m2\n* Weight \\< 350 lbs\n* HbA1c \\< 11%\n* Hemoglobin \\>= 12 g/dl\n\nExclusion Criteria -- Type 1 Diabetes:\n\n* Recent diagnosis (within 3 months) of Diabetic Ketoacidosis (DKA)\n* Severe illness\n* Pregnancy, nursing\n* Anemia\n* Allergy to shellfish or iodine\n* Claustrophobia or implantable metal devices (MRI contraindications)\n* High blood pressure (greater than 130/80 mm Hg)\n* Elevated Urine Albumin-to-Creatinine Ratio (UACR) (\\>30 mg/g) or estimated Glomerular Filtration Rate (eGFR) \\<90 ml/min/1.73 m2\n* Taking ACE inhibitors (ACEis), Angiotensin receptor blockers (ARBs), diuretics, Sodium Glucose Transporter (SGLT) 1/2 blockers\n\nInclusion Criteria -- Healthy Controls:\n\n* No diagnosis of Type 1 or Type 2 Diabetes\n* BMI between 18.5 and 30 kg/m2\n* Weight \\< 350 lbs\n* HbA1c \\< 11%\n* Hemoglobin \\>= 12 g/dl\n\nExclusion Criteria -- Healthy Controls:\n\n* Severe illness\n* Pregnancy, nursing\n* Anemia\n* Allergy to shellfish or iodine\n* Claustrophobia or implantable metal devices (MRI contraindications)\n* High blood pressure (greater than 130/80 mm Hg)\n* Elevated UACR (\\>30 mg/g) or eGFR \\<90 ml/min/1.73 m2\n* Taking ACE inhibitors (ACEis), Angiotensin receptor blockers (ARBs), diuretics, SGLT 1/2 blockers\n\nAdditional exclusion criteria for participants undergoing optional kidney biopsy:\n\n* Evidence of bleeding disorder or complications from bleeding\n* 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\n* Blood urea nitrogen (BUN) \\> 80 gm/dL\n* INR \\> 1.4\n* PTT \\> 35 seconds\n* Hemoglobin (Hgb) \\< 10 mg/dL\n* Platelet count \\< 100,000 / µL\n* Uncontrolled or difficult to control hypertension (\\> 150/90 mmHg at the day of biopsy)\n* eGFR \\< 40 mL/min/1.73m2\n* Single kidney (either by history, documented by prior imaging or ultrasound performed prior to the biopsy)\n* \\> 2 cm discrepancy between left and right kidney sizes based on largest longitudinal diameter determined by ultrasound performed prior to the biopsy.\n* Kidney size: One or both kidneys \\< 9 cm\n* Hydronephrosis or other important renal ultrasound findings such as significant stone disease\n* Any evidence of a current urinary tract infection as indicated on day of biopsy\n* Clinical evidence of non-diabetic renal disease\n* Positive urine pregnancy test or pregnancy'}, 'identificationModule': {'nctId': 'NCT04074668', 'acronym': 'CROCODILE', 'briefTitle': 'Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance', 'organization': {'class': 'OTHER', 'fullName': 'University of Colorado, Denver'}, 'officialTitle': 'CROCODILE Study: Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance', 'orgStudyIdInfo': {'id': '19-1282'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Type 1 Diabetes', 'description': '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).', 'interventionNames': ['Drug: Aminohippurate Sodium Inj 20%', 'Drug: Iohexol Inj 300 milligrams/milliliter (mg/ml)', 'Radiation: PET/CT Scan', 'Procedure: Renal Biopsy']}, {'label': 'Healthy Controls', 'description': '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).', 'interventionNames': ['Drug: Aminohippurate Sodium Inj 20%', 'Drug: Iohexol Inj 300 milligrams/milliliter (mg/ml)', 'Radiation: PET/CT Scan', 'Procedure: Renal Biopsy']}], 'interventions': [{'name': 'Aminohippurate Sodium Inj 20%', 'type': 'DRUG', 'otherNames': ['Sodium 4-amino hippurate (PAH) inj 20% 2 grams (g)/10 milliliters (mL)', 'Para-aminohippurate', 'Aminohippuric acid'], 'description': 'Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)', 'armGroupLabels': ['Healthy Controls', 'Type 1 Diabetes']}, {'name': 'Iohexol Inj 300 milligrams/milliliter (mg/ml)', 'type': 'DRUG', 'otherNames': ['omnipaque 300'], 'description': 'Diagnostic aid/agent used to measure glomerular filtration rate (GFR)', 'armGroupLabels': ['Healthy Controls', 'Type 1 Diabetes']}, {'name': 'PET/CT Scan', 'type': 'RADIATION', 'description': 'Imaging used to visualize the kidneys and quantify renal metabolic activity', 'armGroupLabels': ['Healthy Controls', 'Type 1 Diabetes']}, {'name': 'Renal Biopsy', 'type': 'PROCEDURE', 'description': 'Minimally invasive outpatient procedure to obtain renal tissue after ultrasound visualization.', 'armGroupLabels': ['Healthy Controls', 'Type 1 Diabetes']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': "Children's Hospital Colorado", 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Colorado, Denver', 'class': 'OTHER'}, 'collaborators': [{'name': 'Juvenile Diabetes Research Foundation', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}