Cerebral and Peripheral Perfusion Pilot Study (CAPP)

• ClinicalTrials.gov Identifier: NCT00751907
• Recruitment Status: Completed
• First Posted: September 12, 2008
• Last Update Posted: September 9, 2019
• Sponsor: University of Wisconsin, Madison
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): University of Wisconsin, Madison

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: atorvastatin; Drug: Placebo	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Impact of Atorvastatin on Cerebral Perfusion and Endothelial Function
• Study Start Date: June 2006
• Actual Primary Completion Date: April 2007
• Actual Study Completion Date: April 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: Atorvastatin; 40mg Atorvastatin nightly for 4 months	Drug: atorvastatin; 40mg daily for 4 months; Other Name: Lipitor
Placebo Comparator: Placebo; matching placebo nightly for 4 months	Drug: Placebo; Matching placebo daily for 4 months

Outcome Measures

Primary Outcome Measures :

1. Change in regional cerebral blood flow (rCBF) [ Time Frame: Baseline and 4 months ]
   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

Secondary Outcome Measures :

1. Change in Endothelial function [ Time Frame: Baseline and 4 months ]
   Brachial artery reactivity was used to measure endothelial function

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Wisconsin

Karen Lazar

Madison, Wisconsin, United States, 53705

Sponsors and Collaborators

University of Wisconsin, Madison

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Cynthia M. Carlsson, MD, MS; University of Wisconsin, Madison

More Information

Additional Information:

Wisconsin Alzheimer's Disease Research Center 

Publications of Results:

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 Alzheimer Res. 2012 Oct;9(8):990-7.

Other Publications:

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.

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.

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.

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.

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.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT00751907
• Other Study ID Numbers: IA0138; K23AG026752 ( U.S. NIH Grant/Contract ); Pilot Award ( Other Grant/Funding Number: Wisconsin Comprehensive Memory Program Pilot Award )
• First Posted: September 12, 2008
• Last Update Posted: September 9, 2019
• Last Verified: September 2019

Keywords provided by University of Wisconsin, Madison:

Cerebral blood flow

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Atorvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors