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GLUCOSE METABOLISMNCT02175459

Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy

An observational study of GLUCOSE METABOLISM and DIABETES, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 69 years
Conditions the study is for
GLUCOSE METABOLISM, DIABETES, PANCREATIC ISLETS
How many people
100 participants
Where
1 siteItaly
Study dates
Aug 2010to Dec 2024
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • SCHEDULED FOR PANCREATECTOMY
  • NO DIABETIC and DIABETIC

Who cannot join

  • CHRONIC DESEASES
  • STEROID THERAPY

Trial locations and contacts

1 site in 1 country.

TERESA MEZZA, MD, PHD contact

+39063015 ext. 6664

TERESA.MEZZA@UNICATT.IT

Italy1 site, 1 recruiting

  • Endocrinology - Catholic University

    Rome, RM, 00168

    ANDREA GIACCARI, MD, PHD

    Recruiting

Other trials in Italy

About this study

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.

Keywords
Beta cell function, Islet cell crosstalk, Incretin intraislet System, Biomarkers, MiRNA, ncRNA, Pancreatic exocrine endocrine crosstalk, Diabetes of exocrine pancreas
Medical subject headings
Diabetes Mellitus, Exocrine Pancreatic Insufficiency

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline in metabolic status (normal glucose tolerance, impaired glucose tolerance, diabetes)

    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).

    Measured: baseline, 1 month after surgery and 1year after surgery

Secondary outcomes (5)

  1. Changes in incretin levels from baseline

    Incretin levels (GLP1 and GIP) will be measured during mixed meal test.

    Measured: baseline, 1 months after surgery and 1 year after surgery

  2. Change in insulin secretion from baseline

    Insulin secretion will be measured by Hyperglicemic clamp.

    Measured: baseline, 1 month after surgery and 1 year after surgery

  3. islet cell areas (beta, Alpha and delta cell positive area)

    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.

    Measured: baseline

  4. changes in beta cell function in the context of disease of exocrine pancreas

    Insulin secretion will be measured by Hyperglicemic clamp and ogtt.

    Measured: baseline

  5. changes in intraislet ncRNA in different metabolic status

    ncRNA sequenting in plasma and pancreas samples

    Measured: baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2014 (estimated)
  2. Study startAug 2010
  3. Primary completionDec 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Cross-sectional
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02175459
Sponsor's protocol ID
14081985
Status last verified
May 2024
First submitted
23 Jun 2014
Last updated
23 May 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • Mezza T, Wewer Albrechtsen NJ, Di Giuseppe G, Ferraro PM, Soldovieri L, Ciccarelli G, Brunetti M, Quero G, Alfieri S, Nista EC, Gasbarrini A, Tondolo V, Mari A, Pontecorvi A, Giaccari A, Holst JJ. Human subjects with impaired beta-cell function and glucose tolerance have higher levels of intra-islet intact GLP-1. Metabolism. 2025 Feb;163:156087. doi: 10.1016/j.metabol.2024.156087. Epub 2024 Dec 1.

    PubMed 39626843

  • 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.

    PubMed 39342881

  • 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.

    PubMed 33905373

  • 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.

    PubMed 30131390

Questions about this trial

What is this clinical trial studying?

An observational study of GLUCOSE METABOLISM and DIABETES, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact TERESA MEZZA, MD, PHD (+39063015 ext. 6664, TERESA.MEZZA@UNICATT.IT), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline in metabolic status (normal glucose tolerance, impaired glucose tolerance, diabetes) (time frame: baseline, 1 month after surgery and 1year after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02175459, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2024.

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