Ignite Creation Date:
2025-12-24 @ 2:29 PM
Ignite Modification Date:
2026-04-17 @ 12:56 AM
Study NCT ID:
NCT02175459
Status:
RECRUITING
Last Update Posted:
2024-05-23
First Post:
2014-06-23
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D010188', 'term': 'Exocrine Pancreatic Insufficiency'}], 'ancestors': [{'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': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'PANCREAS SAMPLES'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'CROSS_SECTIONAL', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 100}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2010-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-05', 'completionDateStruct': {'date': '2024-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-05-22', 'studyFirstSubmitDate': '2014-06-23', 'studyFirstSubmitQcDate': '2014-06-25', 'lastUpdatePostDateStruct': {'date': '2024-05-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-06-26', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2024-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'change in gene expression analysis among different groups of baseline metabolic status', 'timeFrame': 'baseline', 'description': 'Extract of islet cells will be dissected from pancreatic sections by laser capture microdissection and then extracted RNA will be analyzed by real time PCR analysis.'}], 'primaryOutcomes': [{'measure': 'Change from baseline in metabolic status (normal glucose tolerance, impaired glucose tolerance, diabetes)', 'timeFrame': 'baseline, 1 month after surgery and 1year after surgery', 'description': 'Metabolic status will be determined with oral glucose tolerance test and patients will be classified according their metabolic status (after 1 month and 1 year after surgery).'}], 'secondaryOutcomes': [{'measure': 'Changes in incretin levels from baseline', 'timeFrame': 'baseline, 1 months after surgery and 1 year after surgery', 'description': 'Incretin levels (GLP1 and GIP) will be measured during mixed meal test.'}, {'measure': 'Change in insulin secretion from baseline', 'timeFrame': 'baseline, 1 month after surgery and 1 year after surgery', 'description': 'Insulin secretion will be measured by Hyperglicemic clamp.'}, {'measure': 'islet cell areas (beta, Alpha and delta cell positive area)', 'timeFrame': 'baseline', 'description': 'Pancreas section will be immunostained for insulin, glucagon and somatostatin and Each section will be analyzed separately by measuring total insulin, glucagon or somatostatin positive areas, as well as the total pancreas section area, using Image Pro Plus software version 4. 5.1 . The β, α or δ cell areas will be expressed as percentage of total pancreas section area.'}, {'measure': 'changes in beta cell function in the context of disease of exocrine pancreas', 'timeFrame': 'baseline', 'description': 'Insulin secretion will be measured by Hyperglicemic clamp and ogtt.'}, {'measure': 'changes in intraislet ncRNA in different metabolic status', 'timeFrame': 'baseline', 'description': 'ncRNA sequenting in plasma and pancreas samples'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Beta cell function', 'Islet cell crosstalk', 'Incretin intraislet System', 'Biomarkers', 'MiRNA', 'ncRNA', 'Pancreatic exocrine endocrine crosstalk', 'Diabetes of exocrine pancreas'], 'conditions': ['GLUCOSE METABOLISM', 'DIABETES', 'PANCREATIC ISLETS', 'Exocrine Pancreatic Dysfunction', 'Exocrine Pancreas Conditions', 'Exocrine Pancreatic Insufficiency', 'Endocrine Pancreas Disorder']}, 'referencesModule': {'references': [{'pmid': '39342881', 'type': 'DERIVED', 'citation': 'Quero G, Laterza V, Di Giuseppe G, Lucinato C, Massimiani G, Nista EC, Sionne F, Biffoni B, Brunetti M, Rosa F, De Sio D, Ciccarelli G, Fiorillo C, Menghi R, Langellotti L, Soldovieri L, Gasbarrini A, Pontecorvi A, Giaccari A, Alfieri S, Tondolo V, Mezza T. A single-center prospective analysis of the impact of glucose metabolism on pancreatic fistula onset after pancreaticoduodenectomy for periampullary tumors. Am J Surg. 2024 Dec;238:115987. doi: 10.1016/j.amjsurg.2024.115987. Epub 2024 Sep 24.'}, {'pmid': '33905373', 'type': 'DERIVED', 'citation': 'Mezza T, Ferraro PM, Di Giuseppe G, Moffa S, Cefalo CM, Cinti F, Impronta F, Capece U, Quero G, Pontecorvi A, Mari A, Alfieri S, Giaccari A. Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional beta cells in predicting diabetes. J Clin Invest. 2021 Jun 15;131(12):e146788. doi: 10.1172/JCI146788.'}, {'pmid': '30131390', 'type': 'DERIVED', 'citation': 'Mezza T, Ferraro PM, Sun VA, Moffa S, Cefalo CMA, Quero G, Cinti F, Sorice GP, Pontecorvi A, Folli F, Mari A, Alfieri S, Giaccari A. Increased beta-Cell Workload Modulates Proinsulin-to-Insulin Ratio in Humans. Diabetes. 2018 Nov;67(11):2389-2396. doi: 10.2337/db18-0279. Epub 2018 Aug 21.'}]}, 'descriptionModule': {'briefSummary': 'Regeneration of mature cells that produce functional insulin represents a major focus of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes. The capacity to adapt in response to diverse physiological conditions during life and the consequent ability to cope for increased metabolic demands is a distinctive feature of the endocrine pancreas in the regulation of glucose homeostasis. Both beta and alpha cells are dynamically regulated to continually maintain a balance between proliferation, neogenesis, and apoptosis. In this proposal, the investigators will focus on exploring key mechanism(s) that potentially regulate islet cell plasticity in altered glucose metabolic states.\n\nInvestigators will explore in a unique cohort of individuals who undergo duodenal pancretectomy. Prior to their surgery will be performed in vivo studies (Hyperglycemic clamp, Euglycemic Hyperinsulinemic clamp and Mixed Meal Tests) to accurately assess glucose homeostasis parameters to classify each individual into metabolic phenotypes. Then exploit the opportunity to collect pancreas samples from these patients who will be evaluated again after surgery, the investigators will determine the ability of the remnant pancreas to compensate for the acute reduction in islet mass and perform correlations between ex vivo and in vivo parameters.\n\nSpecifically, the patients will be subjected to incretin secretion (mixed meal), metabolic status (OGTT), insulin secretion characteristics (first and second phase responses), β-cell insulin content evaluation (arginine bolus). Subsequently, pancreas samples will be evaluated for morphometry, and proteomics and gene expression analyses of islet cell samples obtain by laser capture will allow a detailed investigation of mechanisms that contribute to islet plasticity. The overall goal of this project is to investigate key mechanisms driving the ability of islet mass to adapt to diverse metabolic states. We aim to explore modifications in gene expression and proteomics and correlate them with specific metabolic phenotypes, in order to determine key regulators of islet morphology.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '69 Years', 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': "Patients scheduled for elective pancreaticoduodenectomy for periampullary neoplasms will be enrolled in the study. Indications for surgery will be periampullary neoplasms, i.e.\n\ntumors of the Vater's ampulla, distal CBD and periampullary duodenum. Patients with pancreatic cancer will be excluded from the study. The metabolic features of all patients will be assessed before and after surgery. The patients will visit the Division of Endocrinology for studies at least 1 week before surgery. Only patients with normal cardiopulmonary and kidney functions, as determined by medical history, physical examination, screening blood tests, electrocardiogram and urinalysis, and not on any antidiabetic medications will be enrolled for metabolic assessments before and after surgery. Each subject will undergo, on separate days, a hyperinsulinemic euglycemic clamp, a hyperglycemic clamp and a mixed meal test one week before and after a variable period of recovery from the surgical procedure.", 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* SCHEDULED FOR PANCREATECTOMY\n* NO DIABETIC and DIABETIC\n\nExclusion Criteria:\n\n* CHRONIC DESEASES\n* STEROID THERAPY'}, 'identificationModule': {'nctId': 'NCT02175459', 'briefTitle': 'Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy', 'organization': {'class': 'OTHER', 'fullName': 'Fondazione Policlinico Universitario Agostino Gemelli IRCCS'}, 'orgStudyIdInfo': {'id': '14081985'}}, 'contactsLocationsModule': {'locations': [{'zip': '00168', 'city': 'Rome', 'state': 'RM', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': 'ANDREA GIACCARI, MD, PHD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Endocrinology - Catholic University', 'geoPoint': {'lat': 41.89193, 'lon': 12.51133}}], 'centralContacts': [{'name': 'TERESA MEZZA, MD, PHD', 'role': 'CONTACT', 'email': 'TERESA.MEZZA@UNICATT.IT', 'phone': '+39063015', 'phoneExt': '6664'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fondazione Policlinico Universitario Agostino Gemelli IRCCS', 'class': 'OTHER'}, 'collaborators': [{'name': 'Joslin Diabetes Center', 'class': 'OTHER'}, {'name': 'University of Siena', 'class': 'OTHER'}, {'name': 'University of Copenhagen', 'class': 'OTHER'}, {'name': 'Istituto di Neuroscienze Consiglio Nazionale delle Ricerche', 'class': 'NETWORK'}, {'name': 'University of Pisa', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'associate professor', 'investigatorFullName': 'Giaccari Andrea', 'investigatorAffiliation': 'Fondazione Policlinico Universitario Agostino Gemelli IRCCS'}}}}