Clinical trial NCT02639130: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: Gastric Inhibitory Polypeptide (GIP)
Glucagon-Like Peptide 1 (GLP-1)
DPP-4 inhibition; Exendin [9-39]
Gastric emptying
Glucagon
Incretin
Insulin Secretion
Normal glucose-tolerant
Lead sponsor: Diabeteszentrum Bad Lauterberg im Harz
Sponsor class: OTHER
First posted: 2015-12-24
Enrollment: 67
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Ratio of integrated insulin secretion rates (total AUC ISR) over 4 hour following the meal
timeFrame: 4 hour following the meal
measure: total AUC Glucose over 4 hour following the meal
timeFrame: 4 hour following the meal
Secondary outcomes:
Other outcomes:
Locations:
city: Bad Lauterberg
country: Germany
facility: Diabeteszentrum Bad Lauterberg
state: Niedersachsen
Study officials:
affiliation: Diabeteszentrum Bad Lauterberg
name: Michael A. Nauck, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.