Assessment of Pancreatic Beta Cell Mass and Function by Positron Emission Tomography Imaging in Human Diabetes Mellitus

March 14, 2025 updated by: Riccardo Bonadonna, Azienda Ospedaliero-Universitaria di Parma

Assessment of Pancreatic Beta Cell Mass and Function with the Aid of Positron Emission Tomography Imaging in Human Diabetes Mellitus

The goals of this project are to build an experimental tool to dissect out in vivo pancreatic beta cell mass (BCM) and beta cell function (BCF) and to assess for the first time these two determinants of beta cell functional mass (BCFxM) in obesity and in various stages of type 1 and type 2 diabetes mellitus.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Pancreatic beta cell functional mass (BCFxM) can be loosely defined as the product of beta cell mass (BCM) multiplied by beta cell function (BCF). Current in vivo methods (e.g. hyperglycemic clamp, intravenous glucose tolerance test, oral glucose tolerance test, mixed meal tolerance test) actually assess BCFxM, not beta cell function per se. Loss of BCFxM is at the heart of the etiology and pathogenesis of both type 1 (2) and type 2 diabetes mellitus. In the former, destruction of beta cell mass by autoimmune insulitis is the the primary determinant of BCFxM loss. In the latter, beta cell mass loss is about 25-35% and keeps increasing with the duration of the disease, but an additional key role is played by the loss of beta cell function. Previous dogma held that in type 1 diabetes complete destruction of beta cells was achieved within ≈5 years from diagnosis. Recent data have challenged this concept and shown that residues of both beta cells and BCFxM (i.e. nutrient-stimulated C-peptide secretion, which is equimolar and simultaneous to insulin secretion and is a much better biomarker of BCFxM than insulin concentration) are detectable even decades after diagnosis. Exendin-4 has been already labeled with a positron emitting nuclide and made amenable to PET imaging for diagnostic purposes. Under rigorous experimental conditions, beta cell standardized uptake per volume (SUV) of the ligand could be assessed. Furthermore, current PET-CT instruments can also provide a measure of pancreatic volume BCFxM can be determined accurately by mathematical modeling of relatively simple tests, such as a mixed meal.

The investigators will assess the relative roles of beta cell mass (BCM) and beta cell function (BCF) in two polar BCFxM groups : people with long-standing type 1 diabetes (close to 0 BCFxM) and obese people with normal glucose regulation (highest expected BCFxM), i.e. the investigators will test our method in a negative control (type 1 diabetes) and in a strongly positive control (uncomplicated obesity). A group of lean controls will be studied to ascertain that their BCMs, as determined by 68GA-exendin-4 PET-CT, fall, as they should, in the intermediate range between type 1 diabetes and obesity.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Pr
      • Parma, Pr, Italy, 43126
        • Recruiting
        • Azienda Ospedaliero Universitaria di Parma
        • Contact:
        • Contact:
          • Alessandra Dei Cas, PhD
        • Contact:
          • Livia Ruffini, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥18 years; ≤ 75 years
  • Both sexes
  • Good health
  • Absence of exclusion criteria
  • Able to understand methods, goals, and implications of the research and of delivering a free, written informed consent

Exclusion Criteria:

  • Hemoglobin < 12 g/dl
  • HbA1c > 10%
  • Pregnancy or breast-feeding
  • If not in menopause, women not using effective birth control methods or not willing to undergo a pregnancy test
  • History of severe psychiatric disorder or alcohol abuse
  • Recent head traumas (<6 months)
  • Active neurologic diseases
  • Claustrophobia
  • Active malignant neoplasms
  • Severe kidney and/or liver disease
  • Recent (<6 months) major adverse cardiovascular events
  • Heart failure (class NYHA 3-4)
  • Drugs known to affect beta cell function and/or insulin sensitivity
  • Current or past treatment with GLP1R-agonists
  • Intolerance to exenatide
  • Endocrine diseases, other than diabetes mellitus, known to affect beta cell function and/or insulin sensitivity, except well controlled hypothyroidism or adrenal insufficiency
  • COPD on day time oxygen therapy
  • Any current acute disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: long standing type 1 diabetes (> 20 yrs)
68Ga-exendin4 PET-CT scan +mixed meal test
Drug: 68Ga-exendin-4
68Ga-exendin4 PET-CT scan
Other: mixed meal test
before and after a standardized mixed meal venous blood samples will be collected at time intervals to measure plasma glucose, C-peptide,insulin, glucagon, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) curves
Other: newly diagnosed type 1 diabetes (< 5yrs)
68Ga-exendin4 PET-CT scan +mixed meal test
Drug: 68Ga-exendin-4
68Ga-exendin4 PET-CT scan
Other: mixed meal test
before and after a standardized mixed meal venous blood samples will be collected at time intervals to measure plasma glucose, C-peptide,insulin, glucagon, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) curves
Other: long standing type 2 diabetes (> 20 yrs)
68Ga-exendin4 PET-CT scan +mixed meal test
Drug: 68Ga-exendin-4
68Ga-exendin4 PET-CT scan
Other: mixed meal test
before and after a standardized mixed meal venous blood samples will be collected at time intervals to measure plasma glucose, C-peptide,insulin, glucagon, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) curves
Other: newly diagnosed type 2 diabetes (<6 months)
68Ga-exendin4 PET-CT scan +mixed meal test
Drug: 68Ga-exendin-4
68Ga-exendin4 PET-CT scan
Other: mixed meal test
before and after a standardized mixed meal venous blood samples will be collected at time intervals to measure plasma glucose, C-peptide,insulin, glucagon, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) curves
Other: pre-diabetes
68Ga-exendin4 PET-CT scan +mixed meal test
Drug: 68Ga-exendin-4
68Ga-exendin4 PET-CT scan
Other: mixed meal test
before and after a standardized mixed meal venous blood samples will be collected at time intervals to measure plasma glucose, C-peptide,insulin, glucagon, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) curves
Other: hyperinsulinemic
68Ga-exendin4 PET-CT scan +mixed meal test
Drug: 68Ga-exendin-4
68Ga-exendin4 PET-CT scan
Other: mixed meal test
before and after a standardized mixed meal venous blood samples will be collected at time intervals to measure plasma glucose, C-peptide,insulin, glucagon, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) curves
Other: control
68Ga-exendin4 PET-CT scan +mixed meal test
Drug: 68Ga-exendin-4
68Ga-exendin4 PET-CT scan
Other: mixed meal test
before and after a standardized mixed meal venous blood samples will be collected at time intervals to measure plasma glucose, C-peptide,insulin, glucagon, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) curves

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
BCF x M
Time Frame: through study completion, an average of 3 months after enrolment

BCFxM=parameters derived from mixed meal test

Beta cell function(BCF)=BCFxM/BCM
through study completion, an average of 3 months after enrolment
pancreatic beta cell mass (BCM)
Time Frame: through study completion, an average of 3 months after enrolment
Beta cell mass index (BCM) = 68GA-exendin-4 Standard Uptake Value (SUV)*pancreatic volume
through study completion, an average of 3 months after enrolment
pancreatic beta cell function (BCF)
Time Frame: through study completion, an average of 3 months after enrolment
BCFxM/BCM
through study completion, an average of 3 months after enrolment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliero-Universitaria di Parma

Collaborators

University of Parma

Investigators

  • Principal Investigator: Riccardo Bonadonna, MD, Azienda Ospedaliero Universitaria di Parma, University of Parma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2022

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

December 1, 2022

First Submitted That Met QC Criteria

December 20, 2022

First Posted (Actual)

December 22, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 14, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 462 (Alzheimer's Society)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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