Effects of Angiotensin-Converting Enzyme Inhibitor (Ramipril) Therapy on Blood Vessel Inflammation
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Atherosclerosis; Coronary Disease; Vasculitis
Intervention: Ramipril (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
Summary
This study will determine the effects of angiotensin-converting enzyme (ACE) inhibitor (trade
name Ramipril) therapy on inflammation and stiffness of artery walls. These are two risk
factors for developing atherosclerosis-deposits of fatty substances called plaques that can
block the blood vessel, causing a heart attack or stroke. Studies of patients with coronary
artery disease suggest that ACE inhibitor therapy reduces the risk of heart attack and heart
failure. This study will examine the effects of this treatment on the artery walls and on
levels of substances in the blood that indicate blood vessel inflammation.
Patients between 40 and 75 years old with coronary artery disease caused by atherosclerosis
may be eligible for this study. Candidates will be screened with a medical history,
cardiovascular (heart and blood vessel) examination, electrocardiogram and blood tests.
Those enrolled will be randomly assigned to take either an ACE inhibitor pill or a placebo
(look-alike pill with no medicine) once a day for 3 months. No pills will be taken for the
next month, and then participants will take the alternate pill for the next 3 months. That
is, those who took ACE inhibitor for the first 3-month period will take placebo for the
second 3-month period and vice versa. Blood pressures will be taken at the NIH Clinical
Center or by the patient's physician at the end of the first and second weeks of the study.
At the end of 3 weeks, patients will return to the Clinical Center for a blood draw of 6 cc
(1/2 teaspoon) to assess kidney function. In addition, at the end of each 3-month study
period, patients will undergo the following procedures at the Clinical Center:
1. Fasting blood draw of 60 cc (2 ounces) to measure electrolytes (e. g., sodium and
potassium) and blood markers for inflammation
2. Ultrasound (use of sound waves to create pictures) study of the carotid arteries
(arteries in the neck leading to the brain)-An ultrasound probe is applied gently on the
neck, and ultrasound pictures of the right and left carotid arteries are recorded on
tape. Heart activity and blood pressure are monitored during the procedure with an
electrocardiogram and blood pressure cuff.
3. Magnetic resonance imaging (MRI) of the carotid arteries-The patient lies on a table in
a narrow cylinder (the MRI machine) containing a magnetic field. A flexible padded
sensor called a MRI coil is placed over the neck area. Earplugs are placed in the ear
to muffle the loud thumping sounds the machine makes when the magnetic fields are
switched. During the second half of the exam, a contrast agent (gadolinium) is injected
through an intravenous catheter (flexible tube placed in a vein) to brighten the images.
The heart is monitored during the procedure with an electrocardiogram.
Clinical Details
Official title: Effects of Angiotensin Converting Enzyme Inhibitor Therapy on Vascular Inflammation and Compliance
Study design: Treatment, Safety/Efficacy Study
Detailed description:
Vascular inflammation plays a major role in the progression and clinical expression of
atherosclerosis and may contribute to stiffening of arteries that increases the risk of
myocardial infarction and stroke. Therapies that reduce vascular inflammation may reduce
cardiovascular events. Angiotensin converting enzyme (ACE) inhibitor therapy reduces
cardiovascular events in patients with coronary artery disease (CAD), potentially by
reducing vascular oxidant stress and activation of genes that encode protein mediators of
inflammation. However, we found that ACE inhibitor therapy in patients with CAD had no
overall significant effect on serum levels of cell adhesion molecules VCAM-1, ICAM-1, and
E-selectin (surrogate markers of vascular inflammation), although some patients showed a
reduction in levels, suggesting either that these surrogate markers of vascular inflammation
may not accurately reflect reduction in vascular inflammation, or that only a subset of
patients have biological responses that might reduce their cardiovascular risk. The purposes
of this protocol are to determine 1) the effect of ACE inhibitor therapy on vascular
inflammation in patients with coronary artery disease as assessed by MRI of the carotid
arteries, and 2) whether serum markers of inflammation correlate with reduced vascular
inflammation and thus may be suitable surrogates for determining success of ACE inhibitor
therapy.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
All volunteer subjects must be between 40 and 75 years of age with documented CAD, and must
have provided informed, written consent for participation in this study.
Ability to comprehend or willingness to sign the consent form.
No pregnant women or women with child-bearing potential not on effective contraception.
No ACE inhibitor therapy within 6 months.
No renal insufficiency (creatinine greater than 2. 0 mg/dl).
Blood pressure must not be higher than 140/90 on current medical therapy.
No claustrophobia.
No history of involuntary motion disorder.
Specific MRI exclusion criteria (i. e. pacemaker, cochlear implants, AICD, internal infusion
pump, metal implants or clips in field of view).
No systemic inflammatory disorder (e. g, rheumatoid arthritis, periarteritis nodosa,
systemic lupus erythromatosus, temporal arteritis).
No need for chronic NSAID therapy.
Locations and Contacts
National Heart, Lung and Blood Institute (NHLBI), Bethesda, Maryland 20892, United States
Additional Information
Related publications: Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med. 1994 Aug 18;331(7):417-24. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD, Lusis AJ. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation. 1995 May 1;91(9):2488-96. Review. Koh KK, Bui MN, Hathaway L, Csako G, Waclawiw MA, Panza JA, Cannon RO 3rd. Mechanism by which quinapril improves vascular function in coronary artery disease. Am J Cardiol. 1999 Feb 1;83(3):327-31.
Starting date: June 2000
Ending date: February 2002
Last updated: March 3, 2008
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