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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

Tracking Information
First Submitted Date  ICMJE September 15, 2014
First Posted Date  ICMJE September 18, 2014
Last Update Posted Date August 7, 2019
Study Start Date  ICMJE October 2014
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2014)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02244164 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2014)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 17, 2014)
  • Fasting glycemia [ Time Frame: 1 year ]
    Quarterly during 1 years a blood analysis will be done.
  • C-Peptide [ Time Frame: 1 years ]
    Quarterly during 1 year a blood analysis will be done.
  • HbA1c [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Cholesterol [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Calcium [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Phosphorus [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Urea [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Creatininemia [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Bilirubinemia [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Alcaline phosphatase [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Gamma GT [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Alanine aminotransferase [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Asparate aminotransferase [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
  • Lipasemia [ Time Frame: 1 year ]
    Quarterly during 1 year a blood analysis will be done.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Pathophysiological Study of the Increase in Pancreatic Volume in Type 2 Diabetes Treatments.
Official Title  ICMJE Pathophysiological Study of the Increase in Pancreatic Volume in Type 2 Diabetes Treatments.
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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Type 2 Diabetes
  • Incretinomimetics
  • Pancreas
Intervention  ICMJE
  • 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®).
Study Arms  ICMJE
  • Active Comparator: Sulfonylurea
    Patient will received metformine with sulfonylurea
    Interventions:
    • Drug: Incretinomimetics
    • Drug: DPP-4 inhibitors
  • Active Comparator: Incretinomimectics
    Patients will received metformin with sulfonylurea with GLP-1 analogue
    Intervention: Drug: DPP-4 inhibitors
  • Active Comparator: DPP-4 inhibitors
    Patients will received metformin with DPP-4 inhibitors
    Intervention: Drug: Incretinomimetics
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 17, 2014)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Vincent Huberty, MD +3225553715 vincent.huberty@erasme.ulb.ac.be
Contact: Blero Daniel, PhD +3225553712 daniel.blero@erasme.ulb.ac.be
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02244164
Other Study ID Numbers  ICMJE Incretine study
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Erasme University Hospital
Study Sponsor  ICMJE Erasme University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Vincent Huberty, MD Gastroenterology Department Erasme Hospital
PRS Account Erasme University Hospital
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP