Statins and Endothelial Function in Patients With Coarctation of the Aorta

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00767572
• Collaborator: American Heart Association (Other)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 23
• Patients Per Site Per Month: 0.5

Study Details

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
• 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: Aug 1, 2008
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 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 Names: 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 Names: placebo

Outcome Measures

Primary Outcome Measures

1. Pre-post Change in Brachial Artery Reactivity [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	UCSF Medical Center, 505 Parnassus Ave	San Francisco	California	United States	94143

Sponsors and Collaborators

• University of California, San Francisco
• American Heart Association

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00767572
• Other Study ID Numbers: H7151-32792-01
• First Posted: Oct 7, 2008
• Last Update Posted: Oct 14, 2013
• Last Verified: Oct 1, 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; Atorvastatin

Study Results

Participant Flow

Recruitment Details	Patients were recruited from the UCSF Adult Congenital Heart Disease Clinic between July 2008 and July 2009. All reviewed the study protocol and agreed to participate. There was no compensation for study participants.
Pre-assignment Detail	Patients were excluded if they did not have prior repair of aortic coarctation or could not participate in all 4 study visits.

Arm/Group Title	Atorvastatin Then Sugar Pill, or Sugar Pill Then Atorvastatin
Arm/Group Description	Patients were randomized to atorvastatin or placebo once daily for 12 weeks. After a 4 week washout, each participant received the other intervention for 12 weeks. Brachial artery assessment was performed before and after each 12 week intervention.
Period Title: First Intervention (12 Weeks)
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: First Intervention (12 Weeks)
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: First Intervention (12 Weeks)
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Atorvastatin Then Sugar Pill, or Sugar Pill Then Atorvastatin
Arm/Group Description	Patients were randomly assigned to receive atorvastatin or placebo once daily for 12 weeks. After a 4 week washout, each participant received the other intervention for 12 weeks. Brachial artery assessment were performed before and after each 12 week intervention.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35 (8.8)
Sex: Female, Male (Count of Participants)
Female	4 33.3%
Male	8 66.7%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Pre-post Change in Brachial Artery Reactivity
Description	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.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

12 enrolled participants were randomly assigned to receive a 12-week course of either atorvastatin or placebo, followed by a 4-week washout, then 12 weeks on the alternate intervention.

Arm/Group Title	Atorvastatin	Sugar Pill
Arm/Group Description	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.	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.
Measure Participants	12	12
Mean (Standard Deviation) [mm]	3 (1.5)	3 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorvastatin, Sugar Pill
	Comments	Null hypothesis: pre-post brachial artery diameter changes do not differ between placebo and atorvastatin
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	Significance threshold p<0.05
	Method	t-test, 2 sided
	Comments

Adverse Events

Arm/Group Title	Atorvastatin		Sugar Pill
Arm/Group Description	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.		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.
All Cause Mortality
	Atorvastatin		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Atorvastatin		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Atorvastatin		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)

Limitations/Caveats

All patients were enrolled and completed the study interventions and assessments. Technical problems with measurements may have led to some unreliable data.

More Information

Certain Agreements

All Principal Investigators ARE 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.