Arginase Inhibition and Microvascular Endothelial Function in Type 2 Diabetes

NCT ID: NCT02687152

Last Updated: 2016-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2016-01-31

Brief 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.

Detailed 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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Arginase inhibition

N-hydroxyl-nor-L-arginine, i.a. 0.1 mg/min for 120 min

Group Type: EXPERIMENTAL

N-hydroxy-nor-L-arginine

Intervention Type: OTHER

Interventions

N-hydroxy-nor-L-arginine

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

John Pernow

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John Pernow, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

Karolinska Institutet

Stockholm, , Sweden

Countries

Sweden

Other Identifiers

Micro Arginase

Identifier Type: -

Identifier Source: org_study_id