Type1diabetesNCT05662189
Assessment of Pancreatic Beta Cell Mass and Function by Positron Emission Tomography Imaging in Human Diabetes Mellitus
A study testing 68Ga-exendin-4 and mixed meal test in people with Type1diabetes and Type2diabetes, run by Azienda Ospedaliero-Universitaria di Parma at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type1diabetes, Type2diabetes, Pre Diabetes
- What is being tested?
- 68Ga-exendin-4 and mixed meal test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteItaly
- Study dates
- 15 Mar 2022to Dec 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliero Universitaria di Parma
Parma, Pr, 43126
Raffaella Aldigeri, MSc, +390521033306, raffaella.aldigeri@unipr.it
Alessandra Dei Cas, PhD
About this study
Official title: 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.
Read the 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.
- Conditions
- Type1diabetes, Type2diabetes, Pre Diabetes, Hyperinsulinism
- Being tested
- 68Ga-exendin-4, mixed meal test
- Keywords
- diabetes, beta-cell, exendin, PET-CT
- Medical subject headings
- Glucose Intolerance, Hyperinsulinism, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
68Ga-exendin-4Drug
68Ga-exendin4 PET-CT scan
mixed meal testOther
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
| Study group | Role | What they receive |
|---|---|---|
| long standing type 1 diabetes (> 20 yrs) | Other | 68Ga-exendin4 PET-CT scan +mixed meal test Receives: Drug: 68Ga-exendin-4; Other: mixed meal test |
| newly diagnosed type 1 diabetes (< 5yrs) | Other | 68Ga-exendin4 PET-CT scan +mixed meal test Receives: Drug: 68Ga-exendin-4; Other: mixed meal test |
| long standing type 2 diabetes (> 20 yrs) | Other | 68Ga-exendin4 PET-CT scan +mixed meal test Receives: Drug: 68Ga-exendin-4; Other: mixed meal test |
| newly diagnosed type 2 diabetes (<6 months) | Other | 68Ga-exendin4 PET-CT scan +mixed meal test Receives: Drug: 68Ga-exendin-4; Other: mixed meal test |
| pre-diabetes | Other | 68Ga-exendin4 PET-CT scan +mixed meal test Receives: Drug: 68Ga-exendin-4; Other: mixed meal test |
| hyperinsulinemic | Other | 68Ga-exendin4 PET-CT scan +mixed meal test Receives: Drug: 68Ga-exendin-4; Other: mixed meal test |
| control | Other | 68Ga-exendin4 PET-CT scan +mixed meal test Receives: Drug: 68Ga-exendin-4; Other: mixed meal test |
What is being measured
The primary outcome is the main question the study is designed to answer.
BCF x M
BCFxM=parameters derived from mixed meal test
Beta cell function(BCF)=BCFxM/BCM
Measured: through study completion, an average of 3 months after enrolment
pancreatic beta cell mass (BCM)
Beta cell mass index (BCM) = 68GA-exendin-4 Standard Uptake Value (SUV)*pancreatic volume
Measured: through study completion, an average of 3 months after enrolment
pancreatic beta cell function (BCF)
BCFxM/BCM
Measured: through study completion, an average of 3 months after enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2022
- Study start15 Mar 2022
- Primary completionJul 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type1diabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Obese people with normal glucose regulation , patients with long standing or newly diagnosed type 1 diabetes, patients with long standing or newly diagnosed type 2 diabetes, subjects with pre-diabetes, and lean healthy age- and gender-matched controls will participate in two study sessions on two separate days: * Session A (Endocrinology and Metabolic Diseases Unit) - Quantitation of beta cell functional mass (BCFxM) by mixed-meal test * Session B (Nuclear Medicine Unit) - Quantitation of beta cell mass (BCM) by PET-CT scan.
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria di Parma
- Sponsor type
- University, hospital or other
- Collaborators
- University of Parma
- Responsible party
- Principal investigator, Riccardo Bonadonna, Azienda Ospedaliero-Universitaria di Parma
- Investigators
- Riccardo Bonadonna, MD, Principal investigator, Azienda Ospedaliero Universitaria di Parma, University of Parma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05662189
- Sponsor's protocol ID
- 462
- Status last verified
- Mar 2025
- First submitted
- 1 Dec 2022
- Last updated
- 18 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Pancreatic Beta Cell Mass and Function with the Aid of Positron Emission Tomography Imaging in Human Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT05662189
- Acronym / sponsor ID
- 462
- Conditions
- Type1diabetes, Type2diabetes, Pre Diabetes, Hyperinsulinism
- Keywords
- diabetes, beta-cell, exendin, PET-CT
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Azienda Ospedaliero-Universitaria di ParmaUniversity, hospital or other
- Collaborators
- University of Parma
- Study start
- 15 Mar 2022 (actual)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 22 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 7
- Model description
- Obese people with normal glucose regulation , patients with long standing or newly diagnosed type 1 diabetes, patients with long standing or newly diagnosed type 2 diabetes, subjects with pre-diabetes, and lean healthy age- and gender-matched controls will participate in two study sessions on two separate days: * Session A (Endocrinology and Metabolic Diseases Unit) - Quantitation of beta cell functional mass (BCFxM) by mixed-meal test * Session B (Nuclear Medicine Unit) - Quantitation of beta cell mass (BCM) by PET-CT scan.
| Arm | Type | Receives |
|---|---|---|
| long standing type 1 diabetes (> 20 yrs) | Other | Drug: 68Ga-exendin-4, Other: mixed meal test68Ga-exendin4 PET-CT scan +mixed meal test |
| newly diagnosed type 1 diabetes (< 5yrs) | Other | Drug: 68Ga-exendin-4, Other: mixed meal test68Ga-exendin4 PET-CT scan +mixed meal test |
| long standing type 2 diabetes (> 20 yrs) | Other | Drug: 68Ga-exendin-4, Other: mixed meal test68Ga-exendin4 PET-CT scan +mixed meal test |
| newly diagnosed type 2 diabetes (<6 months) | Other | Drug: 68Ga-exendin-4, Other: mixed meal test68Ga-exendin4 PET-CT scan +mixed meal test |
| pre-diabetes | Other | Drug: 68Ga-exendin-4, Other: mixed meal test68Ga-exendin4 PET-CT scan +mixed meal test |
| hyperinsulinemic | Other | Drug: 68Ga-exendin-4, Other: mixed meal test68Ga-exendin4 PET-CT scan +mixed meal test |
| control | Other | Drug: 68Ga-exendin-4, Other: mixed meal test68Ga-exendin4 PET-CT scan +mixed meal test |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 68Ga-exendin-468Ga-exendin4 PET-CT scan | Drug | control, hyperinsulinemic, long standing type 1 diabetes (> 20 yrs), long standing type 2 diabetes (> 20 yrs), newly diagnosed type 1 diabetes (< 5yrs), newly diagnosed type 2 diabetes (<6 months), pre-diabetes |
| mixed meal testbefore 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, hyperinsulinemic, long standing type 1 diabetes (> 20 yrs), long standing type 2 diabetes (> 20 yrs), newly diagnosed type 1 diabetes (< 5yrs), newly diagnosed type 2 diabetes (<6 months), pre-diabetes |
Primary outcome
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
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
pancreatic beta cell function (BCF)
Time frame: through study completion, an average of 3 months after enrolment
BCFxM/BCM
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Riccardo Bonadonna, MD principal investigator
Azienda Ospedaliero Universitaria di Parma, University of Parma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 68Ga-exendin-4 and mixed meal test in people with Type1diabetes and Type2diabetes, run by Azienda Ospedaliero-Universitaria di Parma 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 5 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 18 Mar 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Riccardo Bonadonna, MD (+390521033307, riccardo.bonadonna@unipr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BCF x M (time frame: through study completion, an average of 3 months after enrolment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Mar 2025.