Effects of Angiotensin-Converting Enzyme Inhibitor (Ramipril) Therapy on Blood Vessel Inflammation

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00005928
First received: June 28, 2000
Last updated: March 3, 2008
Last verified: February 2002
  Purpose

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.

Condition Intervention Phase
Atherosclerosis
Coronary Disease
Vasculitis
Drug: Ramipril
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: Effects of Angiotensin Converting Enzyme Inhibitor Therapy on Vascular Inflammation and Compliance

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 25
Study Start Date: June 2000
Estimated Study Completion Date: February 2002
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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  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: NCT00005928

Locations
United States, Maryland
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00005928     History of Changes
Other Study ID Numbers: 000162, 00-H-0162
Study First Received: June 28, 2000
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
ACE Inhibitor
Vascular Inflammation
Vascular Compliance
Cell Adhesion Molecules
Coronary Artery Disease

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Coronary Disease
Coronary Artery Disease
Inflammation
Vasculitis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Myocardial Ischemia
Heart Diseases
Pathologic Processes
Angiotensin-Converting Enzyme Inhibitors
Ramipril
Enzyme Inhibitors
Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014