Correlation Between Plasma- and Endothelial DPP-4 Activity
|Study Design:||Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Plasma and Endothelial Activity of Dipeptidyl Peptidase 4 During Different Doses of Sitagliptin|
- Correlation between the total and intact GLP-1 hormone during different doses of sitagliptin measured as total area under the curve (tAUC) [ Time Frame: GLP.1 total and GLP-1 intact will be calculated based on blood samples at time points: -40,-30,-20,-10,0,10,20,30,40,50,60,75,90,105,120,150,180,240,300,360 on all days ]
- Differences in serum-/plasma concentrations of GLP-1 measured as total Area under the curve (tAUC) [ Time Frame: GLP-1 will be measured at time points(minutes): -40,-30,-20,-10,0,10,20,30,40,50,60,75,90,105,120,150,180,240,300,360 on all days ]
- Differences in glucose measured as total Area under the curve (tAUC) [ Time Frame: Glucose will be measured at time points(minutes): -40,-30,-20,-10,0,10,20,30,40,50,60,75,90,105,120,150,180,240,300,360 on all days ]
- Differences in Insulin measured as total Area under the curve (tAUC) [ Time Frame: Insulin will be measured at time points(minutes): -40,-30,-20,-10,0,10,20,30,40,50,60,75,90,105,120,150,180,240,300,360 on all days ]
|Study Start Date:||May 2013|
|Study Completion Date:||March 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Patients with Type 2 Diabetes Mellitus and healthy control subjects are given tablets of sitagliptin in either a dosage of 25, 100 or 200 mg or a placebo tablet in 4 different days.
In randomized order:
Day 1: tablet of 25 mg of sitagliptin + i.v. GLP-1 infusion Day 2: tablet of 100 mg of sitagliptin + i.v. GLP-1 infusion Day 3: tablet of 200 mg of sitagliptin + i.v. GLP-1 infusion
Other Name: JanuviaDrug: Placebo
Day 4: placebo tablet
The two incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the intestinal L- and K- cells, respectively in response to ingestion of nutrients. The two hormones are able to lower blood glucose levels during high glucose levels - by the so called incretin effect. GIP and GLP-1 are both rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4). The remaining metabolites are without insulinotropic effects. The effect of DPP-4 inhibitors used in treatment of type 2 diabetes relies on their impact on DPP-4 activity.
DPP-4 exists in a soluble form in plasma ad as a membrane-bound form in blood vessels and other tissues. The impact of DPP-4 inhibitors on DPP-4 activity has only been evaluated in plasma. We aim to investigate plasma and endothelial DPP-4 activity (i.e. whole-body DPP-4 activity) in patients with type 2 diabetes during different doses of the DPP-4 inhibitor sitagliptin.
Both healthy control subjects and patients with type 2 diabetes are subjected to 4 experimental days (in a randomized order) with continuous infusion of GLP-1 and pre-treatment with 25 mg sitagliptin, 100 mg sitagliptin, 200 mg sitagliptin and placebo, respectively. Afterwards, we are going to measure the whole-body DPP-4 activity by comparing plasma levels of active (intact) GLP-1 and total GLP-1, and relate to plasma DPP-4 activity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02192853
|Diabetes Research Division, Department of Endocrinology, Gentofte Hospital|
|Hellerup, Denmark, 2900|
|Study Director:||Filip K Knop, MD PhD||Gentofte Hospital|
|Study Chair:||Tina Vilsbøll, MD DMSc||Gentofte Hospital|
|Study Chair:||Asger Lund, MD||Gentofte Hospital|
|Study Chair:||Camilla Andersen, Med.stud.||Gentofte Hospital|
|Study Chair:||Jens Juul Holst, MD DMSc||Institute of biomedical sciences, University of Copenhagen|
|Principal Investigator:||Emilie Skytte Andersen, Med.stud.||Gentofte Hospital|