Arginase Inhibition and Microvascular Endothelial Function in Type 2 Diabetes

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Other: N-hydroxy-nor-L-arginine

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska Institutet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arginase inhibition; N-hydroxyl-nor-L-arginine, i.a. 0.1 mg/min for 120 min	Other: N-hydroxy-nor-L-arginine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cutaneous microvascular endothelial function	Laser Doppler flow rate	2 hours

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: John Pernow, MD, PhD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: February 9, 2016
• First Submitted That Met QC Criteria: February 16, 2016
• First Posted (Estimate): February 22, 2016

Study Record Updates

• Last Update Posted (Estimate): February 22, 2016
• Last Update Submitted That Met QC Criteria: February 16, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: Micro Arginase

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No