The Role of Endogenous Glucagon-like Peptide 1 (GLP-1) in Type 2 Diabetes Mellitus (T2DM) (DFG_5)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Joerg Schirra, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT01449019
First received: October 2, 2011
Last updated: October 5, 2011
Last verified: October 2011
  Purpose

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).


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: exendin(9-39)amide
Drug: saline
Other: duodenal meal
Other: duodenal saline
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • The incretin effect [ Time Frame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Plasma concentrations of glucagon [ Time Frame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion ] [ Designated as safety issue: No ]
    The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.

  • Plasma concentrations of insulin [ Time Frame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion ] [ Designated as safety issue: No ]
    The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.

  • Plasma concentrations of C-peptide [ Time Frame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion ] [ Designated as safety issue: No ]
    The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.

  • Plasma concentrations of Glucagon-like peptide-1(7-36) (GLP-1(7-36)) [ Time Frame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion ] [ Designated as safety issue: No ]
    The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.

  • Plasma concentrations of Glucose-dependent insulinotropic polpypeptide (GIP) [ Time Frame: Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion ] [ Designated as safety issue: No ]
    The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.


Enrollment: 24
Study Start Date: December 2006
Study Completion Date: July 2010
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: intravenous infusion Drug: exendin(9-39)amide
intravenous infusion of exendin(9-39)
Drug: saline
intravenous infusion of saline
Experimental: intraduodenal perfusion Other: duodenal meal
duodenal perfusion of a meal
Other: duodenal saline
duodenal perfusion of saline

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01449019

Locations
Germany
Ludwig Maximilians-University, Clinical Research Unit
Munich, Germany, 80999
Clinical Research unit, Dept. of Internal Medicine II - Großhadern, University of Munich
Munich, Germany, 81377
Sponsors and Collaborators
Ludwig-Maximilians - University of Munich
Investigators
Principal Investigator: Joerg Schirra, MD Clinical Research Unit (CRU), Department of Internal Medicine, Campus Großhadern, Clinical Center of Ludwig-Maximilians-University of Munich
  More Information

No publications provided by Ludwig-Maximilians - University of Munich

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Joerg Schirra, Principal investigator, Clinical Professor, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT01449019     History of Changes
Other Study ID Numbers: DPI
Study First Received: October 2, 2011
Last Updated: October 5, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ludwig-Maximilians - University of Munich:
GLP-1
Exendin(9-39)
Insulin
Glucagon
T2DM
incretin effect
human physiology

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glucagon
Glucagon-Like Peptide 1
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Incretins

ClinicalTrials.gov processed this record on July 24, 2014