Effect of Valsartan on Carotid Artery Disease
Condition: Carotid Artery Diseases; Atherosclerosis
MeSH terms: Carotid Artery Diseases; Atherosclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      The EFFERVESCENT trial is designed to evaluate the effects of a specific ARB, called
      valsartan, on atherosclerosis. The investigators want to know if treatment with valsartan
      will increase the blood levels of markers responsible for repair of the vessel wall, reduce
      oxidation and inflammation, improve the function of the blood vessels, and arrest or slow
      down the progression of atherosclerosis over time.
    

Detailed description: 
      Atherosclerosis or 'hardening of the arteries' is a process that ultimately leads to the
      development of heart attacks, strokes, poor circulation, and death. Millions of Americans are
      affected by this progressive disease of the arteries. Researchers have tried to understand
      the very complex processes that lead to hardening of the arteries. Part of this research has
      taught the investigators that there are specific molecules that can cause damage or injury to
      the vessel wall by increasing oxidation and inflammation which, in turn, leads to
      atherosclerosis. Other molecules and cells have been found that can actually repair the
      vessel wall.

      Currently, the best treatment the investigators have for preventing or slowing
      atherosclerosis is to control the patients' risk factors such as high blood pressure,
      diabetes, or cholesterol levels using prevention and specific drugs. Angiotensin receptor
      blockers (ARBs) are a class of drugs that have been shown in clinical trials to have many
      beneficial effects in patients with high blood pressure, advanced heart diseases (such as
      after heart attack and heart failure), and diabetes. However, whether these drugs will also
      be useful in people with early signs of hardening of the arteries, measured as a thickening
      of the carotid (neck) arteries is unknown, and is the purpose of this study.

      The EFFERVESCENT trial is designed to evaluate the effects of a specific ARB, called
      valsartan, on atherosclerosis. The investigators want to know if treatment with valsartan
      will increase the blood levels of markers responsible for repair of the vessel wall, reduce
      oxidation and inflammation, improve the function of the blood vessels, and arrest or slow
      down the progression of atherosclerosis over time.

      In this study, the investigators will recruit subjects who have a hardening or thickening of
      their carotid arteries, one of the main blood vessels in the neck. People will be screened
      with ultrasound or sonar examination for this. Two-thirds of those eligible for participation
      will receive valsartan while the remaining one-third will receive a placebo pill. The
      investigators and subjects will be unaware of which drug is being given until the end of the
      study. The study will last for 2 years. Half of the individuals will also be treated with a
      statin drug (used for cholesterol reduction) and the remaining individuals will not be on a
      statin.

      The investigators will measure carotid artery thickening with magnetic resonance imaging
      (MRI); forearm blood vessel function using ultrasound; and they will perform blood tests to
      measure oxidation and inflammation in the blood stream and circulation stem cells that are
      responsible for healing. These tests will be repeated at 3 months, 1 year and 2 years after
      starting treatment. The investigators will also collect blood for genotyping where the DNA
      will be stored for future analysis to study whether subjects' genotype alters their
      susceptibility to treatments. The investigators' hypothesis is that ARB treated individuals
      will have less oxidation and inflammation, higher levels of stem cells, and a slower
      progression of arterial thickening.

      Finding an early treatment for atherosclerosis would hopefully prevent future strokes, heart
      attacks, and deaths leading to improved longevity and reduced medical expenditure.
    

Intervention name(s): Valsartan; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Valsartan was titrated to a target dose of 320 mg orally daily; A matched placebo pill will be given orally daily.
Other intervention name(s): Diovan is a brand name of Valsartan
Intervention MeSH terms: Valsartan
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Angiotensin receptor blockade; Oxidative stress; Endothelial dysfunction