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

NCT ID: NCT01449019

Last Updated: 2011-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2010-07-31

Brief 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).

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

intravenous infusion

Group Type: ACTIVE_COMPARATOR

exendin(9-39)amide

Intervention Type: DRUG

intravenous infusion of exendin(9-39)

saline

Intervention Type: DRUG

intravenous infusion of saline

intraduodenal perfusion

Group Type: EXPERIMENTAL

duodenal meal

Intervention Type: OTHER

duodenal perfusion of a meal

duodenal saline

Intervention Type: OTHER

duodenal perfusion of saline

Interventions

exendin(9-39)amide

intravenous infusion of exendin(9-39)

Intervention Type: DRUG

saline

intravenous infusion of saline

Intervention Type: DRUG

duodenal meal

duodenal perfusion of a meal

Intervention Type: OTHER

duodenal saline

duodenal perfusion of saline

Intervention Type: OTHER

Eligibility Criteria

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).

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Joerg Schirra

Principal investigator, Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joerg Schirra, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Research Unit (CRU), Department of Internal Medicine, Campus Großhadern, Clinical Center of Ludwig-Maximilians-University of Munich

Locations

Ludwig Maximilians-University, Clinical Research Unit

Munich, , Germany

Clinical Research unit, Dept. of Internal Medicine II - Großhadern, University of Munich

Munich, , Germany

Countries

Germany

References

Woerle HJ, Carneiro L, Derani A, Goke B, Schirra J. The role of endogenous incretin secretion as amplifier of glucose-stimulated insulin secretion in healthy subjects and patients with type 2 diabetes. Diabetes. 2012 Sep;61(9):2349-58. doi: 10.2337/db11-1701. Epub 2012 Jun 20.

Reference Type: DERIVED

PMID: 22721966 (View on PubMed)

Other Identifiers

DPI

Identifier Type: -

Identifier Source: org_study_id