Type 2 DiabetesNCT02244164
Pathophysiological Study of the Increase in Pancreatic Volume in Type 2 Diabetes Treatments.
A study testing Incretinomimetics and DPP-4 inhibitors in people with Type 2 Diabetes and Incretinomimetics, run by Erasme University Hospital at 1 site in Belgium.
Trial summary
Incretinomimetics and inhibitors of dipeptidyl peptidase-4 (DPP-4) are new treatments for diabetes. Previous retrospective studies have shown that these treatments induced an increase in pancreatic mass with potentially a risk for pancreatitis and development of precancerous lesions. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 2 Diabetes, Incretinomimetics, Pancreas
- What is being tested?
- Incretinomimetics and DPP-4 inhibitors
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteBelgium
- Study dates
- Oct 2014to 13 Feb 2023
- Phase
- Interventional
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes inadequately controlled or intolerant to metformin
- Obtaining informed consent
- Aged between 18 and 70 years
- BMI between 20 and 45 kg / m²
Who cannot join
- Contraindication to nuclear magnetic resonance (NMR):
- Carrying a metallic foreign body (pacemaker, valve, intraocular equipment, clips)
- Allergy to Gadolinium / Secretin
- Pregnancy or breastfeeding
- Contraindication to treatment with incretinomimetic:
- Hypersensitivity to the active substance or to any of the excipients
Show all 11Show fewer
- Severe Gastroparesis
- Severe renal impairment
- History of Surgery (gastroduodenal, pancreatic or ileocecal)
- Presence or history of pancreatic disease
- Active alcoholism
Trial locations and contacts
1 site in 1 country.
About this study
Incretinomimetics and inhibitors of dipeptidyl peptidase-4 (DPP-4) are new treatments for diabetes. Previous retrospective studies have shown that these treatments induced an increase in pancreatic mass with potentially a risk for pancreatitis and development of precancerous lesions.
The aim of our study is to provide a better understanding of the pathophysiological mechanisms of increased volume and / or pancreatic exocrine secretion when exposed to certain treatment of type 2 diabetes.
Read the detailed description
The incretinomimetics and the inhibitors of dipeptidyl peptidase-4 (DPP-4) are new treatments for diabetes. The incretinomimetics are analogs of Glucagon Like Peptide 1 (GLP-1), secreted from endocrine L-cells of the colon and terminal ileum peptide. Serum GLP-1 increase rapidly after a meal. But its degradation is also fast. It acts on the hypothalamus by reducing appetite and food intake, on the stomach by delaying gastric emptying and the level of beta islet cells by inducing the synthesis and secretion of insulin (1). The incretinomimetics currently marketed in Belgium (March 2014) are exenatide (Byetta ®), liraglutide (Victoza ®), lixisenatide (Lyxumia ®) and very soon (April 2014) extended-release exenatide (Bydureon ®). The DPP-4 prevent the degradation of GLP-1. The DPP-4 currently marketed (March 2014) are sitagliptin (Januvia ®), vildagliptin (Galvus ®), saxagliptin (Onglyza ®) and (Trajenta ®) linagliptin.
In diabetic patients, these treatments allow a significant reduction in fasting plasma glucose and postprandial, with a low risk of hypoglycemia and no weight gain (and sometimes weight loss) (2).
Their place in the management of type 2 diabetes is considered or in combination with metformin, when diabetes is inadequately controlled despite maximal dose of the latter, or when patients are intolerant to metformin.
A study to evaluate the safety of 'incretinomimetics therapy "showed an increase in pancreatic weight of 40% (3). Indeed, in a cohort of 34 pancreatic organ donors from brain death, 20 patients were diabetic and 8 as incretin mimetics for over 1 year. An increase in pancreatic mass on average 40% was observed compared to diabetic patients without this treatment.
This study also demonstrated an increase in the mass of beta cells without restoring insulin function. The advanced for this mass increase without a significant increase of cell size is a hypothesis decreased apoptosis of beta cells.
Furthermore there is also an increase in the mass of cells producing α intraductulaire cell proliferation. This would be responsible for the onset of pancreatitis but also the appearance of endocrine microadenomas. The same study (3) also observed an increase in cell proliferation in the exocrine compartment of the pancreas (ductal and acinar cells) induced by incretinomimetic and an increased frequency of lesions potentially pre-cancerous PanIN 1 and 2 with this treatment.
Another study (4) by the same group of researchers showed that GLP-1 induced ductal cell growth in rats treated with high-dose exenatide for 12 weeks. It could therefore, by ductal obstruction induce pancreatitis.
All of these studies therefore warns about these new treatments potentially inducers of different pancreatic lesions.
The aim of our study is to provide a better understanding of the pathophysiological mechanisms of increased volume and / or pancreatic exocrine secretion when exposed to certain treatment of type 2 diabetes.
- Conditions
- Type 2 Diabetes, Incretinomimetics, Pancreas
- Being tested
- Incretinomimetics, DPP-4 inhibitors
- Keywords
- Type 2 Diabetes, Incretinomimetics, DPP-4 inhibitors, Pancreas, PanIN, RMN, Lipasemia
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IncretinomimeticsDrug
Also called - exenatide (Byetta®), - liraglutide (Victoza®), - lixisenatide (Lyxumia®), - exenatide extended-release (Bydureon®).
DPP-4 inhibitorsDrug
Also called - sitagliptine (Januvia®), - vildagliptine (Galvus®), - saxagliptine (Onglyza®), - linagliptine (Trajenta®).
| Study group | Role | What they receive |
|---|---|---|
| Sulfonylurea | Active comparator | Patient will received metformine with sulfonylurea Receives: Drug: Incretinomimetics; Drug: DPP-4 inhibitors |
| Incretinomimectics | Active comparator | Patients will received metformin with sulfonylurea with GLP-1 analogue Receives: Drug: DPP-4 inhibitors |
| DPP-4 inhibitors | Active comparator | Patients will received metformin with DPP-4 inhibitors Receives: Drug: Incretinomimetics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volumetric measurement of the pancreas
A RMN will be done before and 1 year after the treatment. A comparative mesure of pancreatic volume will be performed.
Measured: 1 year
Secondary outcomes (1)
Quantitative response to secretin
A RMN with injection of secretin will be done before and after the treatment. A quantitative evaluation of secretin response will be performed.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2014 (estimated)
- Study startOct 2014
- Primary completion13 Feb 2023
- Study completion13 Feb 2023
Why it stopped: Recruitment too slow
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies 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
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasme University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent Huberty, MD, Principal investigator, Gastroenterology Department Erasme Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02244164
- Sponsor's protocol ID
- Incretine study
- Status last verified
- Feb 2023
- First submitted
- 15 Sep 2014
- Last updated
- 16 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006 Nov 11;368(9548):1696-705. doi: 10.1016/S0140-6736(06)69705-5.
PubMed 17098089Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007 Jul 11;298(2):194-206. doi: 10.1001/jama.298.2.194.
PubMed 17622601Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M, Butler PC. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes. 2013 Jul;62(7):2595-604. doi: 10.2337/db12-1686. Epub 2013 Mar 22.
PubMed 23524641Butler PC, Elashoff M, Elashoff R, Gale EA. A critical analysis of the clinical use of incretin-based therapies: Are the GLP-1 therapies safe? Diabetes Care. 2013 Jul;36(7):2118-25. doi: 10.2337/dc12-2713. Epub 2013 May 3.
PubMed 23645885
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pathophysiological Study of the Increase in Pancreatic Volume in Type 2 Diabetes Treatments.
- ClinicalTrials.gov ID
- NCT02244164
- Acronym / sponsor ID
- Incretine study
- Conditions
- Type 2 Diabetes, Incretinomimetics, Pancreas
- Keywords
- Type 2 Diabetes, Incretinomimetics, DPP-4 inhibitors, Pancreas, PanIN, RMN, Lipasemia
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment too slow
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Erasme University HospitalUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- 13 Feb 2023 (actual)
- Study completion
- 13 Feb 2023 (actual)
- First posted
- 18 Sep 2014 (estimated)
- 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.
Incretinomimetics and inhibitors of dipeptidyl peptidase-4 (DPP-4) are new treatments for diabetes. Previous retrospective studies have shown that these treatments induced an increase in pancreatic mass with potentially a risk for pancreatitis and development of precancerous lesions.
The aim of our study is to provide a better understanding of the pathophysiological mechanisms of increased volume and / or pancreatic exocrine secretion when exposed to certain treatment of type 2 diabetes.
Detailed description
The incretinomimetics and the inhibitors of dipeptidyl peptidase-4 (DPP-4) are new treatments for diabetes. The incretinomimetics are analogs of Glucagon Like Peptide 1 (GLP-1), secreted from endocrine L-cells of the colon and terminal ileum peptide. Serum GLP-1 increase rapidly after a meal. But its degradation is also fast. It acts on the hypothalamus by reducing appetite and food intake, on the stomach by delaying gastric emptying and the level of beta islet cells by inducing the synthesis and secretion of insulin (1). The incretinomimetics currently marketed in Belgium (March 2014) are exenatide (Byetta ®), liraglutide (Victoza ®), lixisenatide (Lyxumia ®) and very soon (April 2014) extended-release exenatide (Bydureon ®). The DPP-4 prevent the degradation of GLP-1. The DPP-4 currently marketed (March 2014) are sitagliptin (Januvia ®), vildagliptin (Galvus ®), saxagliptin (Onglyza ®) and (Trajenta ®) linagliptin.
In diabetic patients, these treatments allow a significant reduction in fasting plasma glucose and postprandial, with a low risk of hypoglycemia and no weight gain (and sometimes weight loss) (2).
Their place in the management of type 2 diabetes is considered or in combination with metformin, when diabetes is inadequately controlled despite maximal dose of the latter, or when patients are intolerant to metformin.
A study to evaluate the safety of 'incretinomimetics therapy "showed an increase in pancreatic weight of 40% (3). Indeed, in a cohort of 34 pancreatic organ donors from brain death, 20 patients were diabetic and 8 as incretin mimetics for over 1 year. An increase in pancreatic mass on average 40% was observed compared to diabetic patients without this treatment.
This study also demonstrated an increase in the mass of beta cells without restoring insulin function. The advanced for this mass increase without a significant increase of cell size is a hypothesis decreased apoptosis of beta cells.
Furthermore there is also an increase in the mass of cells producing α intraductulaire cell proliferation. This would be responsible for the onset of pancreatitis but also the appearance of endocrine microadenomas. The same study (3) also observed an increase in cell proliferation in the exocrine compartment of the pancreas (ductal and acinar cells) induced by incretinomimetic and an increased frequency of lesions potentially pre-cancerous PanIN 1 and 2 with this treatment.
Another study (4) by the same group of researchers showed that GLP-1 induced ductal cell growth in rats treated with high-dose exenatide for 12 weeks. It could therefore, by ductal obstruction induce pancreatitis.
All of these studies therefore warns about these new treatments potentially inducers of different pancreatic lesions.
The aim of our study is to provide a better understanding of the pathophysiological mechanisms of increased volume and / or pancreatic exocrine secretion when exposed to certain treatment of type 2 diabetes.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sulfonylurea | Active comparator | Drug: Incretinomimetics, Drug: DPP-4 inhibitorsPatient will received metformine with sulfonylurea |
| Incretinomimectics | Active comparator | Drug: DPP-4 inhibitorsPatients will received metformin with sulfonylurea with GLP-1 analogue |
| DPP-4 inhibitors | Active comparator | Drug: IncretinomimeticsPatients will received metformin with DPP-4 inhibitors |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Type 2 diabetes inadequately controlled or intolerant to metformin
- Obtaining informed consent
- Aged between 18 and 70 years
- BMI between 20 and 45 kg / m²
Key exclusion criteria (11 listed)
- Contraindication to nuclear magnetic resonance (NMR):
- Carrying a metallic foreign body (pacemaker, valve, intraocular equipment, clips)
- Allergy to Gadolinium / Secretin
- Pregnancy or breastfeeding
- Contraindication to treatment with incretinomimetic:
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 |
|---|---|---|
| IncretinomimeticsAlso: - exenatide (Byetta®), - liraglutide (Victoza®), - lixisenatide (Lyxumia®), - exenatide extended-release (Bydureon®). | Drug | DPP-4 inhibitors, Sulfonylurea |
| DPP-4 inhibitorsAlso: - sitagliptine (Januvia®), - vildagliptine (Galvus®), - saxagliptine (Onglyza®), - linagliptine (Trajenta®). | Drug | Incretinomimectics, Sulfonylurea |
Primary outcome
Volumetric measurement of the pancreas
Time frame: 1 year
A RMN will be done before and 1 year after the treatment. A comparative mesure of pancreatic volume will be performed.
1 secondary outcome
Quantitative response to secretin
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Recruitment too slow). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2023.
- Results publication: PubMed 17098089Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006 Nov 11;368(9548):1696-705. doi: 10.1016/S0140-6736(06)69705-5.
- Results publication: PubMed 17622601Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007 Jul 11;298(2):194-206. doi: 10.1001/jama.298.2.194.
- Results publication: PubMed 23524641Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M, Butler PC. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes. 2013 Jul;62(7):2595-604. doi: 10.2337/db12-1686. Epub 2013 Mar 22.
- Results publication: PubMed 23645885Butler PC, Elashoff M, Elashoff R, Gale EA. A critical analysis of the clinical use of incretin-based therapies: Are the GLP-1 therapies safe? Diabetes Care. 2013 Jul;36(7):2118-25. doi: 10.2337/dc12-2713. Epub 2013 May 3.
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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. This study is not recruiting at the moment.
Vincent Huberty, MD principal investigator
Gastroenterology Department Erasme Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Incretinomimetics and DPP-4 inhibitors in people with Type 2 Diabetes and Incretinomimetics, run by Erasme University Hospital at 1 site in Belgium.
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 4 inclusion and 11 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: stopped early, as of the sponsor's last update on 16 Feb 2023. 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 Belgium. 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?
The study was stopped early (reason given: Recruitment too slow). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volumetric measurement of the pancreas (time frame: 1 year). 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 NCT02244164, 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 16 Feb 2023.