Effect of Valsartan on Carotid Artery Disease

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00208767
• Collaborator: (none)
• Enrollment: 120
• Location: 1
• Arms: 2
• Duration (Months): 57
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Carotid Artery Diseases; Atherosclerosis	Drug: Valsartan; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Valsartan on Endothelial Function, Oxidative Stress, Carotid Atherosclerosis, and Endothelial Progenitor Cells (EFFERVESCENT)
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Diovan is a brand name of Valsartan
Placebo Comparator: Placebo Patients received a placebo instead of Valsartan	Drug: Placebo; A matched placebo pill will be given orally daily.

Outcome Measures

Primary Outcome Measures

1. Change in the Mean Vessel Wall Area (VMA) of the Carotid Bulb From Baseline to 2 Years [Baseline, 2 years]

   The PI will measure carotid artery thickening with magnetic resonance imaging.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Emory University School of Medicine	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University

Investigators

• Principal Investigator: Arshed Quyyumi, MD, Emory University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Arshed A. Quyyumi, Professor of Medicine, Emory University
• ClinicalTrials.gov Identifier: NCT00208767
• Other Study ID Numbers: IRB00024913; CVAL489AUS51
• First Posted: Sep 21, 2005
• Last Update Posted: Dec 8, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Arshed A. Quyyumi, Professor of Medicine, Emory University: Angiotensin receptor blockade; Oxidative stress; Endothelial dysfunction
• Additional relevant MeSH terms: Carotid Artery Diseases; Atherosclerosis; Valsartan

Study Results

Participant Flow

Recruitment Details	Emory Healthcare sites or by advertisement between March 2005 and October 2008.
Pre-assignment Detail	60 of the enrolled subjects were already on long-term statin therapy and were stratified for statin use before randomization. Subjects on statin therapy were switched to simvastatin 40 mg daily unless they were already on high dose statin therapy and thus were placed on 80 mg daily of simvastatin for the duration of the study.

Arm/Group Title	Valsartan	Placebo
Arm/Group Description	Valsartan titrated up to 320 mg orally daily Valsartan: Valsartan was titrated to a target dose of 320 mg orally daily	Patients received a placebo instead of Valsartan
Period Title: Overall Study
STARTED	80	40
COMPLETED	53	33
NOT COMPLETED	27	7

Baseline Characteristics

Arm/Group Title	Valsartan	Placebo	Total
Arm/Group Description	Valsartan titrated up to 320 mg orally daily Valsartan: Valsartan was titrated to a target dose of 320 mg orally daily	Patients received a placebo instead of Valsartan	Total of all reporting groups
Overall Participants	80	40	120
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (9)	62 (9)	60 (9)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	80 100%	40 100%	120 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	38 47.5%	21 52.5%	59 49.2%
Male	42 52.5%	19 47.5%	61 50.8%
Region of Enrollment (participants) [Number]
United States	80 100%	40 100%	120 100%

Outcome Measures

1. Primary Outcome

Title	Change in the Mean Vessel Wall Area (VMA) of the Carotid Bulb From Baseline to 2 Years
Description	The PI will measure carotid artery thickening with magnetic resonance imaging.
Time Frame	Baseline, 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valsartan	Placebo
Arm/Group Description	Valsartan titrated up to 320 mg orally daily Valsartan: Valsartan was titrated to a target dose of 320 mg orally daily	Patients received a placebo instead of Valsartan
Measure Participants	49	27
Mean (Standard Deviation) [mm2]	-6.7 (2.4)	3.4 (3.1)

Adverse Events

Arm/Group Title	Valsartan		Placebo
Arm/Group Description	Valsartan titrated up to 320 mg orally daily Valsartan: Valsartan was titrated to a target dose of 320 mg orally daily		Patients received a placebo instead of Valsartan
All Cause Mortality
	Valsartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Valsartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/80 (3.8%)		0/40 (0%)
Cardiac disorders
Stroke	1/80 (1.3%)	1	0/40 (0%)	0
Injury, poisoning and procedural complications
Majory injury/accident	1/80 (1.3%)	1	0/40 (0%)	0
Respiratory, thoracic and mediastinal disorders
Death	1/80 (1.3%)	1	0/40 (0%)	0
Other (Not Including Serious) Adverse Events
	Valsartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.