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

NCT01449019 | Completed Phase 1 DMC

• 1 other identifier: DPI
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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

Keywords

GLP-1; Exendin(9-39); Insulin; Glucagon; T2DM; incretin effect; human physiology

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Plasma concentrations of glucagon

  Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion

• Plasma concentrations of insulin

  Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion

• Plasma concentrations of C-peptide

  Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion

• Plasma concentrations of Glucagon-like peptide-1(7-36) (GLP-1(7-36))

  Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion

• Plasma concentrations of Glucose-dependent insulinotropic polpypeptide (GIP)

  Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion

Study Arms (2)

intravenous infusion

ACTIVE COMPARATOR

Drug: exendin(9-39)amide; Drug: saline

intraduodenal perfusion

EXPERIMENTAL

Other: duodenal meal; Other: duodenal saline

Interventions

exendin(9-39)amide DRUG

intravenous infusion of exendin(9-39)

intravenous infusion

saline DRUG

intravenous infusion of saline

intravenous infusion

duodenal meal OTHER

duodenal perfusion of a meal

intraduodenal perfusion

duodenal saline OTHER

duodenal perfusion of saline

intraduodenal perfusion

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (2)

Ludwig Maximilians-University, Clinical Research Unit

Munich, 80999, Germany

Location

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

Munich, 81377, Germany

Location

Related Publications (1)

• 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.

  PMID: 22721966 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

exendin (9-39); Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Joerg Schirra, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, Clinical Professor

Study Record Dates

• First Submitted: October 2, 2011
• First Posted: October 7, 2011
• Study Start: December 1, 2006
• Primary Completion: August 1, 2007
• Study Completion: July 1, 2010
• Last Updated: October 7, 2011

Record last verified: 2011-10

Locations

DE (2)