Clinical trial NCT00569465: N-Acetylcysteine and Arginine Administration in Diabetic Patients
Official title: Effects of Arginine and N-Acetylcysteine Administration on Nitric Oxide Production and Arterial Blood Pressure in Hypertensive Diabetic Patients.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Hypertension
Keywords: nitric oxide
oxidative stress
diabetes
hypertension
endothelial dysfunction
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2007-12-07
Enrollment: 24
Sex: MALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: arterial blood pressure decrease
timeFrame: 6 months
Secondary outcomes:
measure: oxidative parameters decrease
timeFrame: 6 months
Other outcomes:
Locations:
city: Turin
country: Italy
facility: "San Giovanni Battista" Hospital of Turin
Study officials:
affiliation: University of Turin, Italy
name: Valentino Martina, MD
role: PRINCIPAL_INVESTIGATOR
References: