The Role of Endogenous Glucagon-like Peptide 1 (GLP-1) in Type 2 Diabetes Mellitus (T2DM)

Diabetes Mellitus, Type 2 Clinical Trial

— DFG_5  

Official title:

The Contribution of Glucagon-like Peptide 1 (GLP-1) to the Entero-insulinar Axis in Healthy Subjects and Patients With Type 2 Diabetes Mellitus (T2DM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01449019
• Other study ID #: DPI
• Status: Completed
• Phase: Phase 1
• First received: October 2, 2011
• Last updated: October 5, 2011
• Start date: December 2006
• Est. completion date: July 2010

Study information

• Verified date: October 2011
• Source: Ludwig-Maximilians - University of Munich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine the contribution of endogenous Glucagon-like peptide 1 (GLP-1) to the postprandial secretion of insulin and glucagon and the incretin effect in healthy subjects and patients with type 2 diabetes mellitus (T2DM).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2010
• Est. primary completion date: August 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

• male or female (postmenopausal, surgically sterile or using double-barrier method of contraception) healthy subjects and patients with type 2 diabetes mellitus (T2DM)

• must be able to complete a 1 week wash-out of current anti-diabetic medications

• Age 30-70 years

• HbA1c (Hemoglobin A1c) =11% at screening

• Body mass index (BMI) <40 kg/m2

• Patients with type 2 diabetes mellitus (T2DM): Must have a fasting blood glucose of =12.2 mmol/L (240 mg/dL) at screening

• Able to provide written informed consent prior to study participation

• Able to communicate well with the investigator and comply with the requirements of the study

Exclusion Criteria:

• Patients with type 1 diabetes mellitus (T1DM), diabetes as a result of pancreatic injury, or secondary forms of diabetes (eg Cushing, acromegaly)

• Need for insulin within the previous 3 months

• Use of Thiazolidinediones in the previous 4 weeks

• Significant concomitant disease or complications of diabetes (i.e. nephropathy, autonomic dysfunction, orthostasis).

• Treatment with systemic steroids and thyroid hormone (unstable dosage).

• Patients with any history of gastrointestinal surgery, e.g. partial bowel resections, partial gastric resections, etc.

• Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.

• Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.

• Significant illness within the two weeks prior to dosing.

• Past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome.

• History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug.

• history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;

• history or clinical evidence of pancreatic injury or pancreatitis;

• history or presence of impaired renal function as indicated by abnormal creatinine or urea val-ues or abnormal urinary constituents (e.g., albuminuria);

• evidence of urinary obstruction or difficulty in voiding at screening;

• Polymorphonuclears <1500/µL at inclusion or platelet count < 100,000/µL at screening and baseline.

• History of immunocompromise.

• Evidence of liver disease as indicated by abnormal transaminases and alkaline phosphatase exceeding twice the upper limit of the normal range, and serum bilirubin should not exceed the value of 27 µmol/L (1.6 mg/dL).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• exendin(9-39)amide
intravenous infusion of exendin(9-39)
• saline
intravenous infusion of saline

Other:
• duodenal meal
duodenal perfusion of a meal
• duodenal saline
duodenal perfusion of saline

Locations

Country	Name	City	State
Germany	Clinical Research unit, Dept. of Internal Medicine II - Großhadern, University of Munich	Munich
Germany	Ludwig Maximilians-University, Clinical Research Unit	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incretin effect	The incretin effect is the difference between postprandial plasma concentrations of insulin and C-peptide, respectively, and those during the isoglycemic fasting control experiment. The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	No
Secondary	Plasma concentrations of glucagon	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	No
Secondary	Plasma concentrations of insulin	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	No
Secondary	Plasma concentrations of C-peptide	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	No
Secondary	Plasma concentrations of Glucagon-like peptide-1(7-36) (GLP-1(7-36))	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	No
Secondary	Plasma concentrations of Glucose-dependent insulinotropic polpypeptide (GIP)	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	No