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

• ClinicalTrials.gov Identifier: NCT02639130
• Recruitment Status: Completed
• First Posted: December 24, 2015
• Last Update Posted: August 16, 2016
• Sponsor: Diabeteszentrum Bad Lauterberg im Harz
• Information provided by (Responsible Party): Michael A. Nauck, Diabeteszentrum Bad Lauterberg im Harz

Tracking Information

• First Submitted Date: December 17, 2015
• First Posted Date: December 24, 2015
• Last Update Posted Date: August 16, 2016
• Study Start Date: February 2008
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GLP-1 Mediating DPP-4 Inhibition in Type 2 Diabetes
• 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
• 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: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Type 2 Diabetes

Intervention

• 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

• 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, Kothe 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 20, 2015): 67
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: January 2010
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 30 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02639130
• Other Study ID Numbers: DZBL-2007-1
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Michael A. Nauck, Diabeteszentrum Bad Lauterberg im Harz
• Original Responsible Party: Same as current
• Current Study Sponsor: Diabeteszentrum Bad Lauterberg im Harz
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michael A. Nauck, Prof.; Diabeteszentrum Bad Lauterberg

• PRS Account: Diabeteszentrum Bad Lauterberg im Harz
• Verification Date: August 2016