Ramipril and Clopidogrel in Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Type 2 Diabetes and Diabetic Nephropathy

AHEPA University Hospital60 enrolled

Overview

The purpose of this study is to determine whether the combination with ramipril and clopidogrel leads to further improvement of endothelial function, reduction of oxidative stress and reduction of vascular inflammation, compared with ramipril monotherapy, in patients with Diabetes Mellitus type 2 and diabetic nephropathy.

* Cardiovascular disease is the leading cause of deaths in diabetic population with diabetic nephropathy. * Pharmacologic therapy for patients with diabetes and hypertension should be with a regimen that includes either an angiotensin-converting-enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) * Diabetic patients at increased cardiovascular risk should receive an antiplatelet agent for primary prevention. Methods: An open label,randomized, two period cross-over design study, involving patients with type 2 diabetes and diabetic nephropathy. After a 4 weeks wash out period for ACE inhibitors or Angiotensin receptor blockers (week 0, baseline) 60 patients will be randomized to receive ramipril(10 mg) only or ramipril (10 mg) and clopidogrel (75mg) for 12 weeks exchanging their treatment for a further 12 weeks, after a 2 week wash out period for clopidogrel. Patients will be examined and measurements will be taken at baseline (week 0), and at the end of 12, 14, and 26 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Type 2 Diabetic Nephropathy Vascular Disease

Interventions

RamiprilDRUG

Patients will receive 10 mg ramipril throughout the study. Each dose will be taken orally once daily. The duration of treatment with ramipril is 26 weeks

ClopidogrelDRUG

12 weeks treatment with ramipril 10 mg and clopidogrel 75 mg once daily followed by a 2 week wash out period for clopidogrel and subsequently additional 12 weeks treatment wit both drugs after cross over.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: type 2 diabetes patients with diabetic nephropathy in the range of micro- or macroalbuminuria and * HbA1c(glycosylated haemoglobin A1c \<7% * Blood pressure ≤130/80 mmHg * LDL (Low Density Lipoproteins) \<100 mg/dl * Informed consent Exclusion Criteria: * patients with diabetic nephropathy and estimated GFR \<30ml/min with Modification of Diet in Renal Disease equation (MDRD equation) * baseline potassium \> 5.2 meq/L * patients with nephrotic proteinuria defined as albumine to creatinine ratio (ACR)\> 3.5 g/g or as proteinuria \>3.5 g per 1.73 m2 per 24 hours * history or evidence of non-diabetic kidney disease * history of stroke, peripheral artery disease, coronary artery disease * history or evidence of a secondary form of hypertension * history of severe hepatic failure, malignancy, severe endocrinopathy,autoimmune disease or chronic inflammatory disease * any known bleeding or platelet disorder or platelets \<100.000/μL * heart failure in New York Heart Association(NYHA) functional class II-IV * inability or unwillingness on the part of the patient to sign the Patient Consent Form * known hypersensitivity to ramipril or to clopidogrel * Women of child-bearing potential * use of oral anticoagulants or other antithrombotic treatment * use of glitazones * patients receiving statins should be on a stable dose of at least 3 months prior to study initiation and dose should be constant during the study * any surgical or medical condition which in the opinion of the investigator may expose the patient to a higher risk in participation in the study

Locations (2)

AHEPA University Hospital

Thessaloniki, Thessaloniki, Greece

RECRUITING

Aristotle University of Thessaloniki/ AHEPA University Hospital

Thessaloniki, Thessaloniki, Greece

RECRUITING

Outcomes

Primary Outcomes

Changes in Asymmetric dimethylarginine (ADMA) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy

The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in ADMA as biomarker of endothelial dysfunction.

Time frame: Baseline to week 12 and week 14 to week 26

Changes in High-sensitivity C-reactive protein (HsCRP) blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy

The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in hsCRP as biomarker of vascular inflammation

Time frame: Baseline to week 12 and week 14 to week 26

Changes in soluble CD40 Ligand (sCD40L)blood levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy

The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in soluble CD40 Ligand as biomarker of vascular inflammation.

Time frame: Baseline to week 12 and week 14 to week 26

Changes in urine 8-isoprostane-F2 levels after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy

The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in urine 8-isoprostane-F2 as biomarker of oxidative stress.

Time frame: Baseline to week 12 and week 14 to week 26

Reduction in albumine to creatine ratio after the combined treatment with ramipril and clopidogrel compared with ramipril monotherapy

The primary aim is to investigate the effect of the combined treatment with ramipril and clopidogrel versus ramipril monotherapy in albumine to creatine ratio as an index of cardiovascular disease