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Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy

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ClinicalTrials.gov Identifier: NCT02175459
Recruitment Status : Recruiting
First Posted : June 26, 2014
Last Update Posted : January 24, 2018
Sponsor:
Collaborator:
Joslin Diabetes Center
Information provided by (Responsible Party):
Andrea Giaccari, Catholic University of the Sacred Heart

Tracking Information
First Submitted Date June 23, 2014
First Posted Date June 26, 2014
Last Update Posted Date January 24, 2018
Study Start Date August 2010
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 25, 2014)
Change from baseline in metabolic status (normal glucose tolerance, impaired glucose tolerance, diabetes) [ Time Frame: baseline, 1 month after surgery and 1year after surgery ]
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).
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT02175459 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: July 25, 2016)
  • Changes in incretin levels from baseline [ Time Frame: baseline, 1 months after surgery and 1 year after surgery ]
    Incretin levels (GLP1 and GIP) will be measured during mixed meal test.
  • Change in insulin secretion from baseline [ Time Frame: baseline, 1 month after surgery and 1 year after surgery ]
    Insulin secretion will be measured by Hyperglicemic clamp.
  • islet cell areas (beta, Alpha and delta cell positive area) [ Time Frame: baseline ]
    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.
Original Secondary Outcome Measures
 (submitted: June 25, 2014)
  • Chages in incretin levels from baseline [ Time Frame: baseline, 1 months after surgery and 1 year after surgery ]
    Incretin levels (GLP1 and GIP) will be measured during mixed meal test.
  • Change in insulin secretion from baseline [ Time Frame: baseline, 1 month after surgery and 1 year after surgery ]
    Insulin secretion will be measured by Hyperglicemic clamp.
  • islet cell areas (beta, Alpha and delta cell positive area) [ Time Frame: baseline ]
    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.
Current Other Pre-specified Outcome Measures
 (submitted: June 25, 2014)
change in gene expression analysis among different groups of baseline metabolic status [ Time Frame: baseline ]
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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy
Official Title Not Provided
Brief Summary

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.

Investigators 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.

Specifically, 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.

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 Without DNA
Description:
PANCREAS SAMPLES
Sampling Method Probability Sample
Study Population

Patients scheduled for elective pancreaticoduodenectomy for periampullary neoplasms will be enrolled in the study. Indications for surgery will be periampullary neoplasms, i.e.

tumors 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.

Condition
  • GLUCOSE METABOLISM
  • DIABETES
  • PANCREATIC ISLETS
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * 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 β-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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 25, 2014)
100
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2018
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • SCHEDULED FOR ELECTIVE DUODENALPANCREATECTOMY
  • NO DIABETIC

Exclusion Criteria:

  • DIABETES
  • CHRONIC DESEASES
  • STEROID THERAPY
  • PANCREATITIS
  • PANCREATIC CANCER
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 69 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: ANDREA GIACCARI, MD, PHD +39063015 ext 6664 GIACCARI@RM.UNICATT.IT
Listed Location Countries Italy
Removed Location Countries  
 
Administrative Information
NCT Number NCT02175459
Other Study ID Numbers 14081985
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Andrea Giaccari, Catholic University of the Sacred Heart
Study Sponsor Catholic University of the Sacred Heart
Collaborators Joslin Diabetes Center
Investigators Not Provided
PRS Account Catholic University of the Sacred Heart
Verification Date January 2018