Arginase Inhibition in Ischemia-reperfusion Injury

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2013-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The present project is designed to test the hypothesis that arginase contributes to endothelial dysfunction induced by ischemia-reperfusion in patients with coronary artery disease.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Prevention of Contrast-Induced Nephropathy in Diabetic Patients With Undergoing Coronary Angiography

NCT00950079

Contrast Induced Nephropathy

UNKNOWN PHASE4

N-Acetylcysteine and Arginine Administration in Diabetic Patients

NCT00569465

Type 2 Diabetes Mellitus Hypertension

TERMINATED PHASE4

Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease

NCT02791906

Renal Insufficiency, Chronic

TERMINATED PHASE2

Prevention of Contrast-induced Nephropathy in Patients With Acute Myocardial Infarction

NCT01160627

Contrast Induced Nephropathy

COMPLETED NA

The Role of L-arginine in the Endothelial Dysfunction

NCT00583388

Healthy

WITHDRAWN

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Background: Arginase competes with nitric oxide synthase for their common substrate L-arginine. Up-regulation of arginase in coronary artery disease (CAD) and diabetes mellitus may reduce nitric oxide bioavailability contributing to endothelial dysfunction and ischemia-reperfusion injury. Arginase inhibition reduces infarct size in animal models. Therefore the aim of the current study was to investigate if arginase inhibition protects from endothelial dysfunction induced by ischemia-reperfusion in patients with CAD with or without type 2 diabetes.

Methods: Male patients with CAD (n=12) or CAD + type 2 diabetes (n=12), were included in this cross-over study with blinded evaluation. Endothelium-dependent vasodilatation was assessed by flow-mediated dilatation (FMD) of the radial artery before and after 20 min ischemia-reperfusion during intra-arterial infusion of the arginase inhibitor (N-hydroxy-nor-L-arginine, 0.1 mg/min) or saline.

Results: The forearm ischemia-reperfusion was well tolerated. Endothelium-independent vasodilatation was assessed by sublingual nitroglycerin. Ischemia-reperfusion decreased FMD in patients with CAD from 12.7±5.2% to 7.9±4.0% during saline administration (P\<0.05). N-hydroxy-nor-L-arginine administration prevented the decrease in FMD in the CAD group (10.3±4.3% at baseline vs. 11.5±3.6% at reperfusion). Ischemia-reperfusion did not significantly reduce FMD in patients with CAD + type 2 diabetes. However, FMD at reperfusion was higher following nor-NOHA than following saline administration in both groups (P\<0.01). Endothelium-independent vasodilatation did not differ between the occasions.

Conclusions: Inhibition of arginase protects against endothelial dysfunction caused by ischemia-reperfusion in patients with CAD. Arginase inhibition may thereby be a promising therapeutic strategy in the treatment of ischemia-reperfusion injury.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Coronary Artery Disease Type 2 Diabetes Mellitus

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

N-hydroxy-nor-arginine

N-hydroxy-nor-arginine 0.1 mg/ min i.a. for 20 min

Group Type EXPERIMENTAL

N-hydroxy-nor-arginine

Intervention Type DRUG

NaCl

NaCl 0.9%, 6 ml/min i.a. for 20 min

Group Type PLACEBO_COMPARATOR

NaCl

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

N-hydroxy-nor-arginine

Intervention Type DRUG

NaCl

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Coronary artery disease

Exclusion Criteria

* Age \>80 years, Myocardial infarction/unstable angina within 6 weeks prior to the study, Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm, Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol, Participant in an ongoing study, Unwillingness to participate following oral and written information.

Maximum Eligible Age

80 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No