GLP-1 Mediating DPP-4 Inhibition in Type 2 Diabetes

Type 2 Diabetes Clinical Trial

Official title:

Quantification of the Contribution of GLP-1 to Mediating Insulinotropic Effects of DPP-4 Inhibition With Vildagliptin in Healthy Subjects and Type 2-diabetic Patients Using Exendin [9-39] as a GLP-1 Receptor Antagonist

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02639130
• Other study ID #: DZBL-2007-1
• Status: Completed
• Phase: Phase 4
• First received: December 17, 2015
• Last updated: August 15, 2016
• Start date: February 2008
• Est. completion date: January 2010

Study information

• Verified date: August 2016
• Source: Diabeteszentrum Bad Lauterberg im Harz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesGermany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

To determine the extent to which the effects of treatment with LAF237 100 mg QD on glucagon secretion are mediated by Glucagon-like-peptide 1 (GLP-1) in type 2 diabetic patients and healthy subjects.

Description:

Design:

This two center study employs a double blind, placebo controlled, cross-over study in patients with type 2 diabetes (T2D) and healthy volunteers with comparable age, gender and BMI distribution. Subjects (40 patients and 40 healthy volunteers, referred to as subjects in remaining part of the document) will be randomized to 100 mg LAF 237 QD or placebo for two 10-day treatment periods in a cross-over design. Thirty two (32) efficacy evaluable patients are required to complete the study.

Each subjects will participate in an approximate 14-day screening period, a 2-week wash-out period from metformin, a 1-day baseline period and a 10-day treatment period followed by a 2-4 week wash-out period and a second treatment period. An end of study evaluation will be conducted following the completion of the second treatment period or in the event of early withdrawal or termination of the patient.

At screening, subjects meeting inclusion/exclusion criteria will begin a weight maintenance diet containing 50% carbohydrates, 30% protein and 20% fat. Patients will receive guidance on dietary maintenance at screening and will stay on this diet from screening to the end of study evaluation. Following the screening visit, enrolled patients will start a 2 week drug wash-out period where oral hypoglycemic medication will be discontinued.

During the drug wash-out period, all patients will monitor their glucose levels two times a day (prior to breakfast and dinner) using a glucometer. Additionally, at one week intervals, patients will perform a seven point blood glucose test, where glucose measurements will be made prior to and two hours after each meal, and prior to bed. Weekly telephone calls will be made to each patient, where the results of these glucose tests will be recorded. Patients will be discontinued from the study during the wash-out period if fasting glucose levels exceed 200 mg/dl on any two consecutive measurements.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

• Treatment with either diet/exercise or metformin

• HbA1c 6.5 - 9.0 %

• Fasting plasma glucose 6.0 - 11.0 mmol/l

• Body-mass-index 20.0 - 35.0 kg/m²

• Healthy controls were required to have a normal oral glucose tolerance test (75g) and no first-degree relatives with type 2 diabetes nor a personal history of gestational diabetes

Exclusion Criteria:

• Significant heart, kidney (serum creatinine = 123 µmol/l in woman and = 132 µmol/l in men), liver (transaminases < 2fold upper limit of normal) and gastrointestinal disease

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Exendin [9-39]
Exendin [9-39] at 350 and 500 pmol/kg/min for infusion as challenge agent
• Placebo
Placebo infusion as challenge agent

Locations

Country	Name	City	State
Germany	Diabeteszentrum Bad Lauterberg	Bad Lauterberg	Niedersachsen

Sponsors (1)

Lead Sponsor	Collaborator
Diabeteszentrum Bad Lauterberg im Harz

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ratio of integrated insulin secretion rates (total AUC ISR) over 4 hour following the meal		4 hour following the meal	No
Primary	total AUC Glucose over 4 hour following the meal		4 hour following the meal	No