Cerebral and Peripheral Perfusion Pilot Study - Full Text View

Purpose

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	Intervention	Phase
Alzheimer's Disease	Drug: atorvastatin Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease

Drug Information available for: Atorvastatin Atorvastatin calcium Atorvastatin calcium trihydrate

Genetic and Rare Diseases Information Center resources: Familial Alzheimer Disease

U.S. FDA Resources

Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:

Perfusion in the posterior cingulate [ Time Frame: baseline and 4 months ]

Secondary Outcome Measures:

Endothelial function and pulse wave velocity [ Time Frame: Baseline and 4 months ]


Enrollment:	16
Study Start Date:	June 2006
Study Completion Date:	April 2007
Primary Completion Date:	April 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: atorvastatin 40mg daily for 4 months Other Name: Lipitor
Placebo Comparator: 2	Drug: Placebo Matching placebo daily for 4 months

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 will evaluate whether administration of atorvastatin favorably alters blood flow in the brain (measured by magnetic resonance imaging (MRI)) and blood vessel function (measured by ultrasound).

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

Eligibility


Ages Eligible for Study:	40 Years to 65 Years (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

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: NCT00751907

Locations


United States, Wisconsin
University of Wisconsin
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

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


Responsible Party:	Cynthia M. Carlsson, MD, MS, University of Wisconsin School of Medicine and Public Health
ClinicalTrials.gov Identifier:	NCT00751907 History of Changes
Other Study ID Numbers:	IA0138 1R01AG031790 ( U.S. NIH Grant/Contract )
Study First Received:	September 10, 2008
Last Updated:	September 27, 2010

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 Calcium Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 21, 2017

Cerebral and Peripheral Perfusion Pilot Study (CAPP)