Arginase Inhibition and Microvascular Endothelial Function in Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Effect of Arginase Inhibition on Microvascular Endothelial Function in Patients With Type 2 Diabetes and Microvascular Dysfunction.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02687152
• Other study ID #: Micro Arginase
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 9, 2016
• Last updated: February 16, 2016
• Start date: March 2014
• Est. completion date: January 2016

Study information

• Verified date: February 2016
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial Summary

The present project is designed to test the hypothesis that arginase contributes to microvascular endothelial dysfunction in patients with type 2 diabetes and microvascular complications.

Description:

Background

The development of microvascular complications in diabetes is a complex process, in which endothelial dysfunction is of importance. Emerging evidence suggests that arginase is a key mediator of endothelial dysfunction in type 2 diabetes mellitus (T2DM) by reciprocally regulating nitric oxide bioavailability. The aim of this study was to test the hypothesis that arginase activity is increased and that arginase contributes to microvascular endothelial function in patients with T2DM and microvascular dysfunction.

Method

Microvascular endothelium-dependent and -independent vasodilatation are investigated in patients with T2DM (n =12) and healthy age-matched control subjects (n =12) with laser-Doppler flowmetry during iontophoretic application of acetylcholine and sodium nitroprusside, respectively, before and after intra-arterial administration of the arginase inhibitor N-hydroxy-nor-L-arginine (0.1 mg/min) for 120 min.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2016
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of type 2 diabetes mellitus and microvascular dysfunction defined as microalbuminuria > 3.0 mg/mmol or presence of retinopathy.

Exclusion Criteria:

• Myocardial infarction or unstable angina within the last three months,

• Changed dose of any vasodilator drug during the preceding six weeks,

• Ongoing treatment with warfarin

• Concomitant disease that may have interfered with the possibility for the patients to comply with or complete the study protocol

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Other:
• N-hydroxy-nor-L-arginine

Locations

Country	Name	City	State
Sweden	Karolinska Institutet	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in cutaneous microvascular endothelial function	Laser Doppler flow rate	2 hours	No