Correlation Between Plasma- and Endothelial DPP-4 Activity

NCT02192853 | Completed Phase 4 DMC

• 1 other identifier: H-2-2012-149
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes Mellitus; Glucagon-like peptide 1; Dipeptidyl peptidase 4; Dipeptidyl peptidase 4 inhibitor; sitagliptin; Enzyme activity

Outcome Measures

Primary Outcomes (1)

• Correlation between the total and intact GLP-1 hormone during different doses of sitagliptin measured as total area under the curve (tAUC)

  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

Secondary Outcomes (3)

• Differences in serum-/plasma concentrations of GLP-1 measured as total Area under the curve (tAUC)

  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)

  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)

  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 Arms (2)

Sitagliptin

EXPERIMENTAL

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.

Drug: sitagliptin

placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

sitagliptin 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

Also known as: Januvia

Sitagliptin

Placebo DRUG

Day 4: placebo tablet

placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Nephropathy
• Liver disease
• Inflammatory bowel disease
• Pregnancy

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead

Study Sites (1)

Diabetes Research Division, Department of Endocrinology, Gentofte Hospital

Hellerup, 2900, Denmark

Location

Related Publications (9)

• Deacon CF, Hughes TE, Holst JJ. Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig. Diabetes. 1998 May;47(5):764-9. doi: 10.2337/diabetes.47.5.764.

  PMID: 9588448 BACKGROUND

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

  PMID: 17928588 BACKGROUND

• 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.

  PMID: 18786605 BACKGROUND

• Orskov C, Wettergren A, Holst JJ. Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes. 1993 May;42(5):658-61. doi: 10.2337/diab.42.5.658.

  PMID: 8482423 BACKGROUND

• Nauck MA, Heimesaat MM, Behle K, Holst JJ, Nauck MS, Ritzel R, Hufner M, Schmiegel WH. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab. 2002 Mar;87(3):1239-46. doi: 10.1210/jcem.87.3.8355.

  PMID: 11889194 BACKGROUND

• Gutzwiller JP, Drewe J, Goke B, Schmidt H, Rohrer B, Lareida J, Beglinger C. Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol. 1999 May;276(5):R1541-4. doi: 10.1152/ajpregu.1999.276.5.R1541.

  PMID: 10233049 BACKGROUND

• Vilsboll T, Krarup T, Madsbad S, Holst JJ. Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept. 2003 Jul 15;114(2-3):115-21. doi: 10.1016/s0167-0115(03)00111-3.

  PMID: 12832099 BACKGROUND

• 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.

  PMID: 15655705 BACKGROUND

• 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.

  PMID: 16338283 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Filip K Knop, MD PhD

  Gentofte Hospital

  STUDY DIRECTOR

• 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

  STUDY CHAIR

• Emilie Skytte Andersen, Med.stud.

  Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: intervention was blinded for the participant and the investigator
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research student

Study Record Dates

• First Submitted: January 4, 2014
• First Posted: July 17, 2014
• Study Start: May 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: March 1, 2014
• Last Updated: September 11, 2017

Record last verified: 2017-09

Locations

DK (1)