Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02639130
Recruitment Status : Completed
First Posted : December 24, 2015
Last Update Posted : August 16, 2016
Sponsor:
Information provided by (Responsible Party):
Michael A. Nauck, Diabeteszentrum Bad Lauterberg im Harz

Tracking Information
First Submitted Date  ICMJE December 17, 2015
First Posted Date  ICMJE December 24, 2015
Last Update Posted Date August 16, 2016
Study Start Date  ICMJE February 2008
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2016)
  • Ratio of integrated insulin secretion rates (total AUC ISR) over 4 hour following the meal [ Time Frame: 4 hour following the meal ]
  • total AUC Glucose over 4 hour following the meal [ Time Frame: 4 hour following the meal ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 20, 2015)
Ratio of integrated insulin secretion rates (total AUC ISR) and total AUC Glucose over 4 hour following the meal [ Time Frame: 4 hour following the meal ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE GLP-1 Mediating DPP-4 Inhibition in Type 2 Diabetes
Official Title  ICMJE 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
Brief 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type 2 Diabetes
Intervention  ICMJE
  • Drug: Exendin [9-39]
    Exendin [9-39] at 350 and 500 pmol/kg/min for infusion as challenge agent
    Other Name: (GLP-1 receptor antagonist)
  • Drug: Placebo
    Placebo infusion as challenge agent
Study Arms  ICMJE
  • Active Comparator: Vildagliptin

    After a screening examination, patients were treated with vildagliptin and participated in meal tests (day 9 and 10, respectively), in a crossover design. Between the two treatment periods, there was a ≥ 5 week wash-out period.

    Experimental procedures: Meal test, determination of the rate of gastric emptying. On days 9 and 10 of treatment, the volunteers underwent a mixed meal (one scrambled egg, a slice of ham, 10 g of butter, two slices of toast, 20 g strawberry jam, and 200 ml of unsweetened tea) test in the morning after fasting overnight. 13C-octanoic acid (110 µl/100 mg) was used as label.

    Meal tests were performed (days 9 and 10), without and with a high dose intravenous infusion of exendin [9-39].

    Interventions:
    • Drug: Exendin [9-39]
    • Drug: Placebo
  • Placebo Comparator: Placebo

    After a screening examination, patients were treated with placebo, and participated in meal tests (day 9 and 10, respectively), in a crossover design. Between the two treatment periods, there was a ≥ 5 week wash-out period.

    Experimental procedures: Meal test, determination of the rate of gastric emptying. On days 9 and 10 of treatment, the volunteers underwent a mixed meal (one scrambled egg, a slice of ham, 10 g of butter, two slices of toast, 20 g strawberry jam, and 200 ml of unsweetened tea) test in the morning after fasting overnight. 13C-octanoic acid (110 µl/100 mg) was used as label.

    Meal tests were performed (days 9 and 10), without and with a high dose intravenous infusion of exendin [9-39].

    Interventions:
    • Drug: Exendin [9-39]
    • Drug: Placebo
Publications * Nauck MA, Kind J, Köthe LD, Holst JJ, Deacon CF, Broschag M, He YL, Kjems L, Foley J. Quantification of the Contribution of GLP-1 to Mediating Insulinotropic Effects of DPP-4 Inhibition With Vildagliptin in Healthy Subjects and Patients With Type 2 Diabetes Using Exendin [9-39] as a GLP-1 Receptor Antagonist. Diabetes. 2016 Aug;65(8):2440-7. doi: 10.2337/db16-0107. Epub 2016 Apr 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 20, 2015)
67
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2010
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02639130
Other Study ID Numbers  ICMJE DZBL-2007-1
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Michael A. Nauck, Diabeteszentrum Bad Lauterberg im Harz
Study Sponsor  ICMJE Diabeteszentrum Bad Lauterberg im Harz
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael A. Nauck, Prof. Diabeteszentrum Bad Lauterberg
PRS Account Diabeteszentrum Bad Lauterberg im Harz
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP