Correlation Between Plasma- and Endothelial DPP-4 Activity

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Emilie Skytte Andersen, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT02192853
First received: January 4, 2014
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

The investigators want to estimate both the endothelial and the plasma activity of dipeptidyl peptidase 4 during different doses of sitagliptin in healthy subjects and patients with type 2 diabetes. Furthermore, the investigators want to investigate whether the current clinical dose of 100 mg of sitagliptin is sufficient to inhibit both the plasma and the endothelial activity of the enzyme dipeptidyl peptidase 4.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: sitagliptin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
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.
Drug: sitagliptin

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
Drug: Placebo
Day 4: placebo tablet

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   35 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Caucasians with diet and/or metformin treated patients with type 2 diabetes (diagnosed according to the criterias of the World Health Organization)
  • Normal Hemoglobin
  • Prior Informed Consent

Exclusion Criteria:

  • Nephropathy
  • Liver disease
  • Inflammatory bowel disease
  • Pregnancy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02192853

Locations
Denmark
Diabetes Research Division, Department of Endocrinology, Gentofte Hospital
Hellerup, Denmark, 2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Investigators
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
  More Information

Publications:

Responsible Party: Emilie Skytte Andersen, Research student, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT02192853     History of Changes
Other Study ID Numbers: H-2-2012-149
Study First Received: January 4, 2014
Last Updated: July 16, 2014
Health Authority: Denmark: Ethics Committee
Denmark: Danish Dataprotection Agency

Keywords provided by University Hospital, Gentofte, Copenhagen:
Diabetes Mellitus
Glucagon-like peptide 1
Dipeptidyl peptidase 4
Dipeptidyl peptidase 4 inhibitor
sitagliptin
Enzyme activity

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014