Cerebral and Peripheral Perfusion Pilot Study

Alzheimer's Disease Clinical Trial

— CAPP  

Official title:

Impact of Atorvastatin on Cerebral Perfusion and Endothelial Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00751907
• Other study ID #: IA0138
• Secondary ID: K23AG026752Pilot
• Status: Completed
• Phase: Phase 2
• Start date: June 2006
• Est. completion date: April 2007

Study information

• Verified date: September 2019
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the hypothesis that in middle-aged, asymptomatic, adult children of persons with Alzheimer's disease (AD), atorvastatin therapy will beneficially affect mechanisms thought to contribute to AD risk by improving blood flow in the brain, improving cerebral perfusion, increasing brain activity patterns, and improving blood vessel function.

Description:

Treatment with cholesterol-lowering medications, specifically statins, is associated with up to a 73% reduction in the prevalence of AD, suggesting a potentially promising role for statins in the prevention of AD. In order to better understand the mechanisms through which statins may possibly modify blood AD risk, this study evaluated whether administration of atorvastatin favorably altered blood flow in the brain (measured by magnetic resonance imaging (MRI)) and blood vessel function (measured by ultrasound).

Participants attended 3 visits over the course of the 4-month study. At the initial visit, participants completed a short questionnaire about their past medical history and medication history. At the baseline visit, participants were randomized in a 1:1 ratio to receive atorvastatin 40 mg nightly vs. matching placebo. At baseline and follow-up visits, participants provided an update on medical problems and medications, reviewed any potential side effects, and had fasting blood tests collected for safety monitoring, including liver and muscle enzyme monitoring. In addition, all participants had MRI and ultrasound measures collected.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

Inclusion Criteria:

• Adult (ages 40-65) children of parent with documented Alzheimer's disease

Exclusion Criteria:

• Current use of cholesterol lowering medication

• History of liver disease

• History of adverse reaction to statin medications

• Elevated lab values (CK and creatinine)

• Use of medications that counteract with atorvastatin

• History of dementia

• Currently pregnant

• Use of large quantities of grapefruit juice (more than 1 quart/day)

• Current involvement in another investigational drug study

• Contraindications to MRI

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• atorvastatin
40mg daily for 4 months
• Placebo
Matching placebo daily for 4 months

Locations

Country	Name	City	State
United States	Karen Lazar	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Carlsson CM, Xu G, Wen Z, Barnet JH, Blazel HM, Chappell RJ, Stein JH, Asthana S, Sager MA, Alsop DC, Rowley HA, Fain SB, Johnson SC. Effects of atorvastatin on cerebral blood flow in middle-aged adults at risk for Alzheimer's disease: a pilot study. Curr — View Citation

Newman GC, Delucia-Deranja E, Tudorica A, Hospod FE, Patlak CS. Cerebral blood volume measurements by T*2-weighted MRI and contrast infusion. Magn Reson Med. 2003 Oct;50(4):844-55. — View Citation

Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J; ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003 Apr 5;361(9364):1149-58. — View Citation

Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O, Deanfield JE. Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. Br Heart J. 1995 Sep;74(3):247-53. — View Citation

Stein JH, Keevil JG, Wiebe DA, Aeschlimann S, Folts JD. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation. 1999 Sep 7;100(10):1050-5. — View Citation

Wassmann S, Ribaudo N, Faul A, Laufs U, Böhm M, Nickenig G. Effect of atorvastatin 80 mg on endothelial cell function (forearm blood flow) in patients with pretreatment serum low-density lipoprotein cholesterol levels <130 mg/dl. Am J Cardiol. 2004 Jan 1;93(1):84-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in regional cerebral blood flow (rCBF)	rCBF , a measure of cerebral perfusion, is the primary outcome. rCBF was measured by arterial spin-labeling magnetic resonance imaging and used to evaluate effects of atorvastatin vs placebo	Baseline and 4 months
Secondary	Change in Endothelial function	Brachial artery reactivity was used to measure endothelial function	Baseline and 4 months

External Links

•   Wisconsin Alzheimer's Disease Research Center