N-Acetylcysteine and Arginine Administration in Diabetic Patients (NACARGPAO)

University of Turin

Status and phase: Terminated; Phase 4

Conditions: Hypertension; Type 2 Diabetes Mellitus

Treatments: Drug: Placebo; Drug: Acetylcysteine; Drug: Arginine

Study type: Interventional

Funder types: Other

Identifiers

NCT00569465

EUDRACT 2004-004203-38

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: Male

Ages: 40 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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24 participants in 2 patient groups, including a placebo group

A

Placebo Comparator group

Treatment:

Drug: Placebo

B

Experimental group

Treatment:

Drug: Arginine

Drug: Acetylcysteine