Correlation Between Plasma- and Endothelial DPP-4 Activity

NCT ID: NCT02192853

Last Updated: 2017-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2014-03-31

Brief Summary

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.

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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 tablet in 3 different days.

Group Type: EXPERIMENTAL

sitagliptin

Intervention Type: DRUG

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

placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Day 4: placebo tablet

Interventions

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

Intervention Type: DRUG

Placebo

Day 4: placebo tablet

Intervention Type: DRUG

Other Intervention Names

Januvia

Eligibility 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

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Emilie Skytte Andersen

Research student

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Filip K Knop, MD PhD

Role: STUDY_DIRECTOR

Gentofte Hospital

Tina Vilsbøll, MD DMSc

Role: STUDY_CHAIR

Gentofte Hospital

Asger Lund, MD

Role: STUDY_CHAIR

Gentofte Hospital

Camilla Andersen, Med.stud.

Role: STUDY_CHAIR

Gentofte Hospital

Jens Juul Holst, MD DMSc

Role: STUDY_CHAIR

Institute of biomedical sciences, University of Copenhagen

Emilie Skytte Andersen, Med.stud.

Role: PRINCIPAL_INVESTIGATOR

Gentofte Hospital

Locations

Diabetes Research Division, Department of Endocrinology, Gentofte Hospital

Hellerup, , Denmark

Countries

Denmark

References

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Reference Type: BACKGROUND

PMID: 9588448 (View on PubMed)

Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409-39. doi: 10.1152/physrev.00034.2006.

Reference Type: BACKGROUND

PMID: 17928588 (View on PubMed)

Holst JJ, Vilsboll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol. 2009 Jan 15;297(1-2):127-36. doi: 10.1016/j.mce.2008.08.012. Epub 2008 Aug 20.

Reference Type: BACKGROUND

PMID: 18786605 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 8482423 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Deacon CF. Circulation and degradation of GIP and GLP-1. Horm Metab Res. 2004 Nov-Dec;36(11-12):761-5. doi: 10.1055/s-2004-826160.

Reference Type: BACKGROUND

PMID: 15655705 (View on PubMed)

Herman GA, Stevens C, Van Dyck K, Bergman A, Yi B, De Smet M, Snyder K, Hilliard D, Tanen M, Tanaka W, Wang AQ, Zeng W, Musson D, Winchell G, Davies MJ, Ramael S, Gottesdiener KM, Wagner JA. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther. 2005 Dec;78(6):675-88. doi: 10.1016/j.clpt.2005.09.002.

Reference Type: BACKGROUND

PMID: 16338283 (View on PubMed)

Other Identifiers

H-2-2012-149

Identifier Type: -

Identifier Source: org_study_id