Correlation Between Plasma- and Endothelial DPP-4 Activity
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|ClinicalTrials.gov Identifier: NCT02192853|
Recruitment Status : Completed
First Posted : July 17, 2014
Last Update Posted : September 11, 2017
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes Mellitus||Drug: sitagliptin Drug: Placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Masking Description:||intervention was blinded for the participant and the investigator|
|Official Title:||Plasma and Endothelial Activity of Dipeptidyl Peptidase 4 During Different Doses of Sitagliptin|
|Study Start Date :||May 2013|
|Actual Primary Completion Date :||February 2014|
|Actual Study Completion Date :||March 2014|
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 tablet in 3 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: Januvia
|Placebo Comparator: placebo||
Day 4: placebo tablet
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|