Atorvastatin, Aspirin, Oxidative Stress, Coagulation and Platelet Activation Indexes

NCT01322711 | Unknown Phase 4

• 1 other identifier: ATORVASA
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Primary and secondary prevention trials with statins, as well as with antiplatelet, clearly demonstrated that these drugs are able to reduce cardiovascular events. Even if the principal mechanism of action of statins is to lower cholesterol, other effects, the so-called pleiotropic effects, have been considered as adjunctive properties potentially accounting for the anti-atherosclerotic effect of statins. Inhibition of oxidative stress may be considered an intriguing pleiotropic effect in view of the fact that oxidative stress is thought to be a key event in the initiation and progression of atherosclerotic disease. Reduction of several markers of oxidative stress including isoprostanes, 8-hydroxydeoxyguanosine (8-OHdG), and nitrotyrosine have been observed after statin treatment. NADPH oxidase is among the most important sources of reactive oxygen species involved in atherosclerotic disease. The investigators developed an ELISA to evaluate serum levels of soluble-gp91phox, the catalytic core of phagocyte NADPH oxidase. Recently the investigators showed that statins (30 days treatment) exert an antioxidant effect via inhibition of soluble gp91phox expression. The exact mechanism by which atorvastatin reduces NADPH oxidase, however, is unclear. Recent study showed that statin treatment inhibits leukocyte ROCK activity, a protein kinase implicated in the activation of NADPH oxidase, with a mechanism that seems to be independent from lowering cholesterol. To further study the mechanism(s) implicate in gp91phox downregulation by statin the investigators planned the present study in patients with high risk of vascular events such as hypercholesterolemic and Type 2 Diabetes mellitus patients. In addition the investigators want to evaluate the synergistic role of atorvastatin with aspirin treatment.

Conditions

Type 2 Diabetes Mellitus; Hypercholesterolemia

Keywords

Thromboxane; Aspirin; Atorvastatin; Platelet activation; Thrombin Activation; Oxidative stress

Outcome Measures

Primary Outcomes (1)

• Evaluation of effect of Atorvastatin Therapy in Hypercholesterolemic Patients (n=30) and Diabetic Patients (n=30)

  In Hypercholesterolemic patients (n=30) and in Diabetic patients (n=30) under chronic treatment with low dose aspirin (100 mg daily for at least 30 days), blood and urine samples were taken at each above reported time to evaluate the effect of atorvastatin or no treatment (Diet) on platelet recruitment, platelet and serum isoprostanes, platelet and serum thromboxane A2, platelet and serum NOX2 activation indexes, thrombin activation indexes, urinary excretion of thromboxane and isoprostanes.

  Baseline, 2 hours, 24 hours, 3 days, 7 days, 30 days

Study Arms (2)

Atorvastatin

ACTIVE COMPARATOR

Each day accordingly to randomization patients allocated to Atorvastatin received a pill of 40 mg of atorvastatin. In diabetic patients the concomitant aspirin treatment include a previous 30 days treatment with 100 mg daily of aspirin. All patients followed the diet used in the placebo group.

Drug: Atorvastatin

Diet

PLACEBO COMPARATOR

Low-fat diet with mean macronutrient profiles that were close to the present Adult Treatment Panel III guidelines (7% energy from saturated fat and, 200 mg dietary cholesterol per day)

Drug: Placebo

Interventions

Atorvastatin DRUG

Atorvastatin 40 mg day

Also known as: Totalip 40 mg, Torvast 40 mg

Atorvastatin

Placebo DRUG

Diet

Diet

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with polygenic hypercholesterolemia (LDL-C \> 160 mg/dl)
• Males and Females
• White race
• Sign of the informed consent

You may not qualify if:

• Liver insufficiency
• Serious renal disorders
• Diabetes mellitus
• Arterial hypertension
• History or evidence of previous myocardial infarction or other atherothrombotic diseases
• Any autoimmune diseases
• Cancer
• Present or recent infections
• Patients were taking nonsteroidal antiinflammatory drugs, drugs interfering with cholesterol metabolism, or vitamin supplements
• For T2 Diabetic patients:
• Patients with T2DM diagnosed according to the American Diabetes Association definition
• Treatment with 100 mg/day aspirin from at least 30 days
• Males and Females
• White race
• Sign of the informed consent

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Stefania Basili

Rome, 00161, Italy

Location

Related Publications (3)

• Carnevale R, Pignatelli P, Di Santo S, Bartimoccia S, Sanguigni V, Napoleone L, Tanzilli G, Basili S, Violi F. Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients. Atherosclerosis. 2010 Nov;213(1):225-34. doi: 10.1016/j.atherosclerosis.2010.08.056. Epub 2010 Aug 19.

  PMID: 20832062 BACKGROUND

• Pignatelli P, Carnevale R, Cangemi R, Loffredo L, Sanguigni V, Stefanutti C, Basili S, Violi F. Atorvastatin inhibits gp91phox circulating levels in patients with hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):360-7. doi: 10.1161/ATVBAHA.109.198622. Epub 2009 Dec 3.

  PMID: 19965781 BACKGROUND

• Pignatelli P, Carnevale R, Pastori D, Cangemi R, Napoleone L, Bartimoccia S, Nocella C, Basili S, Violi F. Immediate antioxidant and antiplatelet effect of atorvastatin via inhibition of Nox2. Circulation. 2012 Jul 3;126(1):92-103. doi: 10.1161/CIRCULATIONAHA.112.095554. Epub 2012 May 21.

  PMID: 22615342 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypercholesterolemia

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Stefania Basili, Prof.

  Sapienza-Univerity of Rome

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: March 24, 2011
• First Posted: March 25, 2011
• Study Start: March 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 28, 2015

Record last verified: 2015-05

Locations

IT (1)