Atherosclerosis
Conditions
Brief summary
The purpose of this study is to determine the efficacy of treatment with olmesartan medoxomil, an Angiotensin Receptor Blocker, compared to placebo on the blood levels of surrogate markers of vascular inflammation for atherosclerotic disease. Patients will be randomized to receive either olmesartan medoxomil or placebo for one year.
Interventions
DRUGOlmesartan medoxomil
DRUGPlacebo
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or Females age less than or equal to 18 * TEE-defined Grade III or IV atherosclerotic disease of the thoracic aorta documented within the previous 90 days, or established atherosclerotic disease of the lower extremities as demonstrated by: * a history of lower extremity peripheral vascular surgery for obstructive atherosclerotic disease, or * a history of lower extremity peripheral arterial angioplasty for obstructive atherosclerotic disease, or * a history of lower extremity amputation secondary to atherosclerotic disease, or * an ABI \<0.90 within the previous 90 days, or * a history of claudication in patients with documented coronary artery disease (i.e., history of myocardial infarction, coronary revascularization, or coronary angiography demonstrating at least one obstructive coronary lesion with a 50% or greater stenosis).
Exclusion criteria
* Women of childbearing age who do not agree to utilize protocol approved contraceptive methods. * Average pre-dose SBP \< 100 or DBP \< 60. * Patients with any serious disorder including cardiovascular (ventricular arrhythmias, valvular disease or implantable defibrillator), renal, pulmonary, hepatic, gastrointestinal, endocrine/metabolic (excluding patients with controlled diabetes mellitus), hematologic/oncologic (including an active malignancy other than basal cell carcinoma or non-metastatic prostate cancer), neurologic, and psychiatric diseases. * Patients with a history of MI, PTCA, CABG, heart failure, CVA or TIA within the last 30 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint for the determination of efficacy will be a composite of | — |
| ten circulating surrogate markers of atherosclerosis for vascular inflammation. | — |
| The surrogate markers of vascular inflammation to be used will include | — |
| C-reactive protein, MCP-1, M-CSF, VCAM-1, TNFα, IL-1, E-Selectin, ICAM-1, IL-6 | — |
| and MMP-9. | — |
Secondary
| Measure | Time frame |
|---|---|
| of oxidative stress (GSH/GSSG ratio). | — |
| Composite of adhesion markers (VCAM-1, E-selectin, and ICAM-1). | — |
| Composite of chemoattractant markers (MCP-1, M-CSF). | — |
| Composite of Growth Factor Markers (PDGF, HGF, TGF-β). | — |
| Assessment of atherosclerotic disease severity of the thoracic aorta as | — |
| Serum levels of TGF-β, PDGF, HGF, and PAI-1. | — |
| on the basis of TEE-defined aortic atherosclerosis. | — |
| Assessment of atherosclerotic disease severity of the peripheral arteries | — |
| of the lower extremities as determined by the ankle brachial index (ABI). | — |
| Endothelial function as determined by brachial artery diameter responses to | — |
| hyperemic flow. | — |
| determined by transesophageal echocardiography (TEE) in patients enrolled | — |
| Individual circulating surrogate markers of atherosclerosis listed above | — |
| (C-reactive protein, MCP-1, M-CSF, VCAM-1, TNFα, IL-1, E-Selectin, ICAM-1, | — |
| IL-6 and MMP). | — |
| The ratio of reduced to oxidized glutathione in the plasma as an indicator | — |
Outcome results
None listed