Statins and Endothelial Function in Patients With Coarctation of the Aorta

• ClinicalTrials.gov Identifier: NCT00767572
• Recruitment Status: Terminated
• First Posted: October 7, 2008
• Results First Posted: October 14, 2013
• Last Update Posted: October 14, 2013
• Sponsor: University of California, San Francisco
• Collaborator: American Heart Association
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

Brief Summary:

Coarctation of the aorta (CoA) accounts for approximately 8% of all congenital heart problems. Patients with CoA are well known to have an increased rates of early heart disease, high blood pressure, heart failure and stroke. Abnormal arterial function (dilation and constriction of the blood vessels) has been observed in these patients and likely contributes to the increased risk of cardiovascular problems. However, therapies targeted at improving arterial function have not been investigated in this population. Statin therapy (cholesterol medicines like Lipitor) have been studied in other subgroups of patients with abnormal arterial function and has shown benefit in improving arterial function and reducing risk of cardiovascular problems.

The investigators hypothesize that patients with CoA have abnormal arterial function leading to increased cardiovascular risk. We further hypothesize that statin therapy may improve this problem. We plan to compile a complete database of information regarding these patients cardiovascular health and propose to then examine the effect of atorvastatin (Lipitor) on arterial function as measured by changes in arm arterial function tests.

Condition or disease	Intervention/treatment	Phase
Coarctation of the Aorta	Drug: atorvastatin; Drug: Sugar pill	Phase 4

Detailed Description:

The study design is a randomized double-blind cross over clinical trial. Patients who meet inclusion criteria and no exclusion criteria will be enrolled. They will undergo a baseline cardiovascular assessment including echocardiography, magnetic resonance imaging or magnetic resonance angiography (MRI/MRA), serum blood samples, brachial artery reactivity testing, and carotid intimal media thickness testing. Once they have completed their baseline testing, they will be randomized to either atorvastatin 80mg or placebo. They will complete 12 weeks of therapy and return at the end of 12 weeks to have a repeat brachial artery study and serum studies. There will then be a four week washout period where they take no medication. They will return for a follow up visit at the end of that four week period for repeat baseline brachial artery testing and serum studies. They then will be assigned to the opposite agent they were on previously (so if they originally were on placebo they switch to atorvastatin and vice versa). They will complete another 12 weeks of therapy and return at the end for a final brachial artery study and blood testing.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Effects of Statins on Endothelial Function in Patients With Coarctation of the Aorta
• Study Start Date: August 2008
• Actual Primary Completion Date: July 2010
• Actual Study Completion Date: July 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: atorvastatin; Patients are randomized to either atorvastatin or placebo once daily for 12 weeks. There is a 4 week washout, and then the groups are switched for 12 weeks. Brachial artery assessment will be performed before and after each 12 week period on therapy.	Drug: atorvastatin; Atorvastatin 80mg daily vs. placebo daily X 12 weeks, then 4 week washout period, then cross over groups to complete another 12 weeks. (Total study time is 28 weeks (12+4+12); Other Name: Lipitor
Placebo Comparator: sugar pill; See above. Patients will be randomized to atorvastatin vs. placebo for 12 weeks and after a 4 week washout period the groups will be switched.	Drug: Sugar pill; atorvastatin 80mg daily vs. placebo daily X 12 weeks, then 4 week washout, then cross over groups X 12 weeks. Total study time is 28weeks (12+4+12).; Other Name: placebo

Outcome Measures

Primary Outcome Measures :

1. Pre-post Change in Brachial Artery Reactivity [ Time Frame: Baseline, 12 weeks ]
   Brachial artery reactivity was assessed by Flow-mediated dilatation (FMD), performed before and after the 12 week period on therapy. FMD uses high-frequency ultrasound measurement of changes in brachial artery diameter after a 5-minute blood pressure cuff arterial occlusion. Brachial artery reactivity has been shown to predict long-term cardiovascular events.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• patients over the age of 18 years with repaired coarctation of the aorta (CoA) and willing to participate in all portions of the study including follow up, blood draws, urine sample, echocardiogram, MRI, brachial artery flow-mediated dilatation (FMD) testing, Carotid Intima Media Thickness (CIMT) testing and statin administration.

Exclusion Criteria:

• patients who are pregnant, nursing, or planning on becoming pregnant in the subsequent year
• current smokers
• patients with documented coronary artery disease (CAD), other systemic inflammatory disorder such as systemic lupus erythematosis or rheumatoid arthritis
• patients already on statin therapy or who have had previous adverse effects to statin therapy
• patients with hepatic transaminases >2X the upper limit of normal
• patients with creatinine clearance <60mg/dL
• patients who have implanted devices such as pacemakers or defibrillators that preclude MRI testing
• patients with low blood pressure at baseline (< 90/50)
• patients who are unwilling or unable to comply with the aforementioned portions of the study

Contacts and Locations

Locations

United States, California

UCSF Medical Center, 505 Parnassus Ave

San Francisco, California, United States, 94143

Sponsors and Collaborators

University of California, San Francisco

American Heart Association

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00767572
• Other Study ID Numbers: H7151-32792-01
• First Posted: October 7, 2008
• Results First Posted: October 14, 2013
• Last Update Posted: October 14, 2013
• Last Verified: October 2013

Keywords provided by University of California, San Francisco:

Coarctation of the aorta; cross over design; atorvastatin; endothelial function

Additional relevant MeSH terms:

Aortic Coarctation; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Atorvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors