Effect of Valsartan on Carotid Artery Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Arshed A. Quyyumi, Emory University
ClinicalTrials.gov Identifier:
NCT00208767
First received: September 13, 2005
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Carotid Artery Diseases
Atherosclerosis
Drug: Valsartan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Valsartan on Endothelial Function, Oxidative Stress, Carotid Atherosclerosis, and Endothelial Progenitor Cells (EFFERVESCENT)

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Change in the Mean Vessel Wall Area (VMA) of the Carotid Bulb From Baseline to 2 Years [ Time Frame: Baseline, 2 years ] [ Designated as safety issue: No ]
    The PI will measure carotid artery thickening with magnetic resonance imaging.


Enrollment: 120
Study Start Date: February 2005
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Valsartan
Valsartan titrated up to 320 mg orally daily
Drug: Valsartan
Valsartan was titrated to a target dose of 320 mg orally daily
Other Name: Diovan is a brand name of Valsartan
Placebo Comparator: Placebo
Patients received a placebo instead of Valsartan

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.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • > 0.65 mm intima-media thickness of the carotid artery measured by ultrasound
  • Males aged 21-80 years or women without child bearing potential up to age 80
  • Can be on concomitant therapy with aspirin, thiazide diuretics, calcium antagonists (for treatment of hypertension), or beta-receptor antagonists.
  • May be on statin if on stable dose for at least 2 months before recruitment

Exclusion Criteria:

  • Angiotensin-converting enzyme (ACE) inhibitor or ARB therapy in the previous 3 months.
  • Initiation or change in dose of statin therapy within 2 months before the study
  • Inability to return to Emory for follow-up blood drawing and MR imaging
  • Age < 21 or > 80 years
  • Premenopausal females with potential for pregnancy
  • Current neoplasm
  • Chronic renal failure [creatinine > 2.5 mg/dL]
  • Diabetes with hemoglobin (Hb) A1c > 8.5
  • Anticipated change in lipid lowering therapy
  • Inability to give informed consent
  • MR exclusion criteria
  • Blood pressure > 140 mmHg systolic and > 90 mmHg diastolic
  • Low-density lipoprotein (LDL) cholesterol level >130 mg/dl
  • Acute coronary syndrome within 2 months
  • Acute cerebrovascular accident within 2 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00208767

Locations
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Arshed Quyyumi, MD Emory University
  More Information

No publications provided

Responsible Party: Arshed A. Quyyumi, Professor of Medicine, Emory University
ClinicalTrials.gov Identifier: NCT00208767     History of Changes
Other Study ID Numbers: IRB00024913, CVAL489AUS51
Study First Received: September 13, 2005
Results First Received: September 12, 2014
Last Updated: September 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Angiotensin receptor blockade
Oxidative stress
Endothelial dysfunction

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Carotid Artery Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Valsartan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014