N-Acetylcysteine and Arginine Administration in Diabetic Patients

• Status: Terminated
• Trial end date: 2006-01-01
• Target enrollment: 0
• Participant gender: Male

Summary

It has been demonstrated that the nitric oxide production is reduced in type 2 diabetic patients and that cardiovascular complications represent 80% of the causes of death in these patients. As nitric oxide is able to reduce platelet aggregation, increase the relaxation of smooth muscle cells, and reduce plasminogen activator inhibitor-1 and endothelin, we hypothesized that nitric oxide deficiency is responsable for the cardiovascular disease in type 2 diabetes mellitus. Arginine and N-acetylcysteine, precursor and enhancer of the nitric oxide synthesis respectively, are able to increase nitric oxide production.

Aim of the study is to evaluate the effect of arginine and N-acetylcysteine administration on arterial blood pressure and different metabolic parameters in patients with type 2 diabetes mellitus and hypertension.

Subjects and methods. 24 male subjects, randomly divided in two groups, will be studied. These subjects will undergo a treatment with arginine (1200 mg once a day) plus N-acetylcysteine (600 mg twice a day) or placebo for six months. Basal and final evaluations include:

• general examination

• ABPM (ambulatory blood pressure monitoring)

• HbA1c, total-cholesterol, HDL-cholesterol, LDL-cholesterol, oxidized LDLs, triglycerides, reduced/oxidized glutathione ratio in red blood cells, nitrites/nitrates, asymmetrical and symmetrical dimethyl-arginine, nitrotyrosine, arginine, homocysteine, C-reactive protein, interleukin-6, tumor necrosis factor-α, intercellular and vascular-cell adhesion molecules, plasminogen activator inhibitor-1 and fibrinogen

• the ultrasound assessment of the intima-media thickness after endothelium-dependent flow-mediated vasodilation of the brachial artery

Expected results. Increase of nitric oxide production and reduction of arterial blood pressure and oxidative parameters.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Turin, Italy
• Treatments: Acetylcysteine; N-monoacetylcystine; Nitric Oxide

Criteria

Inclusion Criteria:

• Male subjects

• Age between 40 and 70 years

• Type 2 diabetes mellitus and hypertension

• Mean 24h arterial blood pressure after the wash-out period: systolic >136mmHg and/or diastolic >86 mmHh

• Written informed consent

Exclusion Criteria:

• Female subjects

• Mean 24h arterial blood pressure after the wash-out period: systolic >180 mmHg and/or diastolic >110 mmHg

• Secondary hypertension

• Significative cardiovascular complications of diabetes

• Cancer or severe systemic, hepatic, pulmonary, cardiovascular or diseases

• Actual treatment with nitrates, acetylcysteine or arginine

• Acetylcysteine hypersensitivity

• Psychiatric disturbs, abuse of drugs or alcohol

• Low compliance

• Absence of written informed consent