Ignite Creation Date:
2025-12-24 @ 10:29 PM
Ignite Modification Date:
2025-12-25 @ 8:03 PM
Study NCT ID:
NCT05985135
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-06-04
First Post:
2023-08-02
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Impact of Insulin Deprivation and Hyperglycemia on Plasma Protein Synthesis in People With Type 1 Diabetes Mellitus
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003922', 'term': 'Diabetes Mellitus, Type 1'}], 'ancestors': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D005782', 'term': 'Gels'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D005947', 'term': 'Glucose'}], 'ancestors': [{'id': 'D003102', 'term': 'Colloids'}, {'id': 'D045424', 'term': 'Complex Mixtures'}, {'id': 'D004304', 'term': 'Dosage Forms'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D006601', 'term': 'Hexoses'}, {'id': 'D009005', 'term': 'Monosaccharides'}, {'id': 'D000073893', 'term': 'Sugars'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'HEALTH_SERVICES_RESEARCH', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 70}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-12-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2028-08', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-05-29', 'studyFirstSubmitDate': '2023-08-02', 'studyFirstSubmitQcDate': '2023-08-02', 'lastUpdatePostDateStruct': {'date': '2025-06-04', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-08-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-08', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Protein synthesis', 'timeFrame': 'Approximately 7 hours', 'description': 'Measurement of isotope abundance in peptides derived from the digested proteins'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Continuous subcutaneous insulin infusion', 'Multiple daily injections of insulin'], 'conditions': ['Type 1 Diabetes']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'https://www.mayo.edu/research/clinical-trials', 'label': 'Mayo Clinic Clinical Trials'}]}, 'descriptionModule': {'briefSummary': 'This research is being done to better understand how insulin effects muscle, blood, and the body in people with Type 1 Diabetes.', 'detailedDescription': "Insulin's contribution in controlling glucose homeostasis has been well appreciated but, its role in maintaining proteome homeostasis is less understood. Some animal and human studies have demonstrated that insulin signaling regulates protein synthesis and degradation as well as posttranslational modifications at the tissue level. Insulin's effect on the muscle's mitochondrial proteo-stasis has also been elucidated. Insulin deprivation increases global synthesis of splanchnic proteins based on isotope dilution studies across splanchnic bed. Most plasma proteins are derived from liver and preliminary studies suggest that synthesis rates of some plasma proteins increase while others decrease. Fractional rates of synthesis of various plasma proteins from the liver have been demonstrated in insulin deprivation state. These proteins might be implicated in the development of some of the complications from diabetes mellitus type 1. (T1DM) especially of macrovascular. Researchers have recently developed an isotope-based methodology to simultaneously measure in vivo synthesis rates of multiple plasma proteins in human.\n\nIn order to further investigate the effects of insulin deprivation researchers will apply the novel non-radioactive stable isotope-based approach on the rate of different plasma protein synthesis in T1DM and Diabetes after total pancreatectomy (DATP) in comparison with non-diabetic controls. Researchers will study pancreatectomized people because like T1DM they also are insulin deficient but unlike pancreatectomized people also are deficient in glucagon. Some tantalizing data from many studies indicate that glucagon also have catabolic effect not only on liver derived proteins but also on skeletal muscle-based proteins. Since skeletal muscle has no glucagon receptors, researchers hypothesize that unknown factors are released to the circulation that act on skeletal muscle to release amino acids for consumption in liver. Researchers will measure amino metabolites, acyl carnitines, organic acids, and ceramides in plasma and determine the blood exosome cargo by mass spectrometry-proteins and lipids and miRNA by PCR.\n\nResearchers have previously shown reduced muscle mitochondrial ATP production during insulin deprivation in both T1D humans and diabetic mice and here researchers will measure mitochondrial energy dynamics in all study participants by the established techniques available in our lab."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria - Type 1 Diabetes Group:\n\n\\- Able to provide written consent.\n\nExclusion Criteria - Type 1 Diabetes Group::\n\n* BMI \\< 20 or \\> 32 kg/m\\^2.\n* Celiac disease.\n* Pregnancy.\n* Smoking.\n* Reported history of illicit substance use.\n* History of active cardiovascular, cerebrovascular, or peripheral vascular disease.\n* Active renal disease evidenced by estimated glomerular filtration rate (GFR) \\< 50 mL/min/1.73 m\\^2.\n* Severe peripheral or autonomic neuropathy.\n* Dementia or any other neurologic disease.\n* Uncontrolled psychiatric disease.\n* Any learning disability.\n* Anemia.\n* Thyroid-stimulating hormone (TSH) ≥ 7 or TSH ≤ 7 and free T4 ≤ 0.9.\n* Hemoglobin A1c \\> 9.0%.\n* Type 2 Diabetes Mellitus (T2DM), or impaired fasting glucose.\n* Detectable C peptide.\n\nInclusion Criteria - Control Group:\n\n* Able to provide written consent.\n* T1DM treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) (not Degludec).\n\nExclusion Criteria - Control Group:\n\n* BMI \\< 20 or \\> 32 kg/m\\^2.\n* Celiac disease.\n* Pregnancy.\n* Smoking.\n* Reported history of illicit substance use.\n* History of active cardiovascular, cerebrovascular, or peripheral vascular disease.\n* Active renal disease evidenced by estimated GFR \\< 50 mL/min/1.73 m\\^2.\n* Severe peripheral or autonomic neuropathy.\n* Dementia or any other neurologic disease.\n* Uncontrolled psychiatric disease.\n* Any learning disability.\n* Anemia.\n* TSH ≥ 7 or TSH ≤ 7 and free T4 ≤ 0.9.\n* T2DM, or impaired fasting glucose.'}, 'identificationModule': {'nctId': 'NCT05985135', 'briefTitle': 'Impact of Insulin Deprivation and Hyperglycemia on Plasma Protein Synthesis in People With Type 1 Diabetes Mellitus', 'organization': {'class': 'OTHER', 'fullName': 'Mayo Clinic'}, 'officialTitle': 'Impact of Insulin Deprivation and Hyperglycemia on Plasma Protein Synthesis in People With Type 1 Diabetes Mellitus and Diabetes After Total Pancreatectomy', 'orgStudyIdInfo': {'id': '21-000001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Type 1 Diabetes Mellitus (T1DM) Insulin Deprived', 'description': 'Subjects will have their insulin infusions replaced with saline and have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.', 'interventionNames': ['Procedure: Muscle Biopsy', 'Other: Jell-O with Amino acids']}, {'type': 'EXPERIMENTAL', 'label': 'Type 1 Diabetes Mellitus (T1DM) Insulin Treated', 'description': 'Subjects will continue their baseline insulin infusion while maintaining a target blood glucose range. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.', 'interventionNames': ['Procedure: Muscle Biopsy', 'Other: Jell-O with Amino acids']}, {'type': 'EXPERIMENTAL', 'label': 'Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia', 'description': 'Subjects will be continue their baseline insulin infusion for 2 hours and then receive an intravenous dextrose infusion to maintain elevated blood sugar levels. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.', 'interventionNames': ['Procedure: Muscle Biopsy', 'Other: Jell-O with Amino acids', 'Dietary Supplement: Dextrose']}, {'type': 'OTHER', 'label': 'Non-Diabetic Controls', 'description': 'Subjects will have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.', 'interventionNames': ['Procedure: Muscle Biopsy', 'Other: Jell-O with Amino acids']}, {'type': 'EXPERIMENTAL', 'label': 'Diabetes after Total Pancreatectomized (DATP) Insulin Treated', 'description': 'Subjects will continue their baseline insulin infusion while maintaining a target blood glucose range. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.', 'interventionNames': ['Procedure: Muscle Biopsy', 'Other: Jell-O with Amino acids']}, {'type': 'EXPERIMENTAL', 'label': 'Diabetes after Total Pancreatectomized (DATP) Insulin Deprived', 'description': 'Subjects will have their insulin infusions replaced with saline and have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.', 'interventionNames': ['Procedure: Muscle Biopsy', 'Other: Jell-O with Amino acids']}], 'interventions': [{'name': 'Muscle Biopsy', 'type': 'PROCEDURE', 'description': 'Needle muscle biopsy of the outer thigh muscle', 'armGroupLabels': ['Diabetes after Total Pancreatectomized (DATP) Insulin Deprived', 'Diabetes after Total Pancreatectomized (DATP) Insulin Treated', 'Non-Diabetic Controls', 'Type 1 Diabetes Mellitus (T1DM) Insulin Deprived', 'Type 1 Diabetes Mellitus (T1DM) Insulin Treated', 'Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia']}, {'name': 'Jell-O with Amino acids', 'type': 'OTHER', 'description': 'An amino acid mixture containing 13C6 Lysine isotope label', 'armGroupLabels': ['Diabetes after Total Pancreatectomized (DATP) Insulin Deprived', 'Diabetes after Total Pancreatectomized (DATP) Insulin Treated', 'Non-Diabetic Controls', 'Type 1 Diabetes Mellitus (T1DM) Insulin Deprived', 'Type 1 Diabetes Mellitus (T1DM) Insulin Treated', 'Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia']}, {'name': 'Dextrose', 'type': 'DIETARY_SUPPLEMENT', 'description': 'Intravenous form of sugar', 'armGroupLabels': ['Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia']}]}, 'contactsLocationsModule': {'locations': [{'zip': '55905', 'city': 'Rochester', 'state': 'Minnesota', 'country': 'United States', 'contacts': [{'name': 'Mark Pataky, PhD, MS', 'role': 'CONTACT', 'email': 'pataky.mark@mayo.edu', 'phone': '507-255-8115'}, {'name': 'Rose Decker', 'role': 'CONTACT', 'email': 'bilderback.rose@mayo.edu', 'phone': '507-255-6770'}], 'facility': 'Mayo Clinic', 'geoPoint': {'lat': 44.02163, 'lon': -92.4699}}], 'centralContacts': [{'name': 'Mark Pataky, PhD, MS', 'role': 'CONTACT', 'email': 'pataky.mark@mayo.edu', 'phone': '507-255-8115'}, {'name': 'Rose Decker', 'role': 'CONTACT', 'email': 'bilderback.rose@mayo.edu', 'phone': '507-285-6770'}], 'overallOfficials': [{'name': 'K. Sreekumaran Nair, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Mayo Clinic'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Mayo Clinic', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'K. Sreekumaran Nair', 'investigatorAffiliation': 'Mayo Clinic'}}}}