N-Acetylcysteine and Arginine Administration in Diabetic Patients

NCT00569465 | Terminated Phase 4

• 1 other identifier: EUDRACT 2004-004203-38
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus; Hypertension

Keywords

nitric oxide; oxidative stress; diabetes; hypertension; endothelial dysfunction

Outcome Measures

Primary Outcomes (1)

• arterial blood pressure decrease

  6 months

Secondary Outcomes (1)

• oxidative parameters decrease

  6 months

Study Arms (2)

A

PLACEBO COMPARATOR

Drug: Placebo

B

EXPERIMENTAL

Drug: Arginine; Drug: Acetylcysteine

Interventions

Arginine DRUG

1200 mg, once a day

Also known as: Zentrum

B

Acetylcysteine DRUG

600 mg twice a day

Also known as: Acetilcisteina

B

Placebo DRUG

3 vials a day

A

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Turin, Italy: lead

Study Sites (1)

"San Giovanni Battista" Hospital of Turin

Turin, Turin, 10126, Italy

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension; Diabetes Mellitus

Interventions

Arginine; Acetylcysteine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals

Study Officials

• Valentino Martina, MD

  University of Turin, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 6, 2007
• First Posted: December 7, 2007
• Study Start: January 1, 2005
• Study Completion: January 1, 2006
• Last Updated: December 7, 2007

Record last verified: 2007-12

Locations

IT (1)