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Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02175459
Recruitment Status : Recruiting
First Posted : June 26, 2014
Last Update Posted : January 27, 2020
Joslin Diabetes Center
Information provided by (Responsible Party):
Andrea Giaccari, Catholic University of the Sacred Heart

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.

Condition or disease

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Study Start Date : August 2010
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

Other Outcome Measures:
  1. 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.

Biospecimen Retention:   Samples Without DNA

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Inclusion Criteria:


Exclusion Criteria:


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02175459

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Endocrinology - Catholic University Recruiting
Rome, RM, Italy, 00168
Principal Investigator: ANDREA GIACCARI, MD, PHD         
Sponsors and Collaborators
Catholic University of the Sacred Heart
Joslin Diabetes Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Andrea Giaccari, associate professor, Catholic University of the Sacred Heart Identifier: NCT02175459    
Other Study ID Numbers: 14081985
First Posted: June 26, 2014    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020