N-Acetylcysteine and Arginine Administration in Diabetic Patients

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Arginine and N-Acetylcysteine Administration on Nitric Oxide Production and Arterial Blood Pressure in Hypertensive Diabetic Patients.

Conditions
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Type 2 Diabetes Mellitus, Hypertension

Intervention / Treatment
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* Drug: Arginine
* Drug: Acetylcysteine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br> | Drug: Placebo<br>* 3 vials a day<br>|
| Experimental: B<br> | Drug: Arginine<br>* 1200 mg, once a day<br>* Other names: Zentrum;Drug: Acetylcysteine<br>* 600 mg twice a day<br>* Other names: Acetilcisteina;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| arterial blood pressure decrease |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| oxidative parameters decrease |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nitric oxide, oxidative stress, diabetes, hypertension, endothelial dysfunction