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Trial record 60 of 61 for:    Lixisenatide

Pathophysiological Study of the Increase in Pancreatic Volume in Type 2 Diabetes Treatments.

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ClinicalTrials.gov Identifier: NCT02244164
Recruitment Status : Recruiting
First Posted : September 18, 2014
Last Update Posted : August 7, 2019
Sponsor:
Information provided by (Responsible Party):
Erasme University Hospital

Brief 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.

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.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Incretinomimetics Pancreas Drug: Incretinomimetics Drug: DPP-4 inhibitors Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Pathophysiological Study of the Increase in Pancreatic Volume in Type 2 Diabetes Treatments.
Study Start Date : October 2014
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Sulfonylurea
Patient will received metformine with sulfonylurea
Drug: Incretinomimetics
Other Names:
  • - exenatide (Byetta®)
  • - liraglutide (Victoza®)
  • - lixisenatide (Lyxumia®)
  • - exenatide extended-release (Bydureon®).

Drug: DPP-4 inhibitors
Other Names:
  • - sitagliptine (Januvia®)
  • - vildagliptine (Galvus®)
  • - saxagliptine (Onglyza®)
  • - linagliptine (Trajenta®).

Active Comparator: Incretinomimectics
Patients will received metformin with sulfonylurea with GLP-1 analogue
Drug: DPP-4 inhibitors
Other Names:
  • - sitagliptine (Januvia®)
  • - vildagliptine (Galvus®)
  • - saxagliptine (Onglyza®)
  • - linagliptine (Trajenta®).

Active Comparator: DPP-4 inhibitors
Patients will received metformin with DPP-4 inhibitors
Drug: Incretinomimetics
Other Names:
  • - exenatide (Byetta®)
  • - liraglutide (Victoza®)
  • - lixisenatide (Lyxumia®)
  • - exenatide extended-release (Bydureon®).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Quantitative response to secretin [ Time Frame: 1 year ]
    A RMN with injection of secretin will be done before and after the treatment. A quantitative evaluation of secretin response will be performed.


Other Outcome Measures:
  1. Fasting glycemia [ Time Frame: 1 year ]
    Quarterly during 1 years a blood analysis will be done.

  2. C-Peptide [ Time Frame: 1 years ]
    Quarterly during 1 year a blood analysis will be done.

  3. HbA1c [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  4. Cholesterol [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  5. Calcium [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  6. Phosphorus [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  7. Urea [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  8. Creatininemia [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  9. Bilirubinemia [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  10. Alcaline phosphatase [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  11. Gamma GT [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  12. Alanine aminotransferase [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  13. Asparate aminotransferase [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.

  14. Lipasemia [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Severe Gastroparesis
  • Severe renal impairment
  • History of Surgery (gastroduodenal, pancreatic or ileocecal)
  • Presence or history of pancreatic disease
  • Active alcoholism

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 ClinicalTrials.gov identifier (NCT number): NCT02244164


Contacts
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Contact: Vincent Huberty, MD +3225553715 vincent.huberty@erasme.ulb.ac.be
Contact: Blero Daniel, PhD +3225553712 daniel.blero@erasme.ulb.ac.be

Locations
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Belgium
Gastroenterology Department Erasme Hospital Recruiting
Brussels, Belgium, 1070
Contact: Vincent Huberty, MD    +3225553715    vincent.huberty@erasme.ulb.ac.be   
Sponsors and Collaborators
Erasme University Hospital
Investigators
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Principal Investigator: Vincent Huberty, MD Gastroenterology Department Erasme Hospital

Publications of Results:
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Responsible Party: Erasme University Hospital
ClinicalTrials.gov Identifier: NCT02244164     History of Changes
Other Study ID Numbers: Incretine study
First Posted: September 18, 2014    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: August 2019
Keywords provided by Erasme University Hospital:
Type 2 Diabetes
Incretinomimetics
DPP-4 inhibitors
Pancreas
PanIN
RMN
Lipasemia
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Obesity Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action