Clinical trial NCT01449019: The Role of Endogenous Glucagon-like Peptide 1 (GLP-1) in Type 2 Diabetes Mellitus (T2DM)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: GLP-1
Exendin(9-39)
Insulin
Glucagon
T2DM
incretin effect
human physiology
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2011-10-07
Enrollment: 24
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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).


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).

Primary outcomes:
measure: The incretin effect
timeFrame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion
Secondary outcomes:
measure: Plasma concentrations of glucagon
timeFrame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion
measure: Plasma concentrations of insulin
timeFrame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion
measure: Plasma concentrations of C-peptide
timeFrame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion
measure: Plasma concentrations of Glucagon-like peptide-1(7-36) (GLP-1(7-36))
timeFrame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion
measure: Plasma concentrations of Glucose-dependent insulinotropic polpypeptide (GIP)
timeFrame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Ludwig Maximilians-University, Clinical Research Unit
city: Munich
country: Germany
facility: Clinical Research unit, Dept. of Internal Medicine II - Großhadern, University of Munich
Study officials:
affiliation: Clinical Research Unit (CRU), Department of Internal Medicine, Campus Großhadern, Clinical Center of Ludwig-Maximilians-University of Munich
name: Joerg Schirra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.