Clinical trial NCT00046358: The Effect of Short-Term Statins and NSAIDs on Levels of Beta-Amyloid, a Protein Associated With Alzheimer's Disease
Official title: The Effect of Short-Term Statin and NSAID Treatment on CSF Beta-Amyloid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alzheimer Disease
Keywords: Cerebrospinal Fluid
Cholesterol
Statin
NSAID
Antiinflammatory
Dementia
Alzheimer's Disease
Nonsteroidal Antiinflammatory
Healthy Volunteer
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2002-09-27
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether short-term use of the drugs ibuprofen and lovastatin affects levels of a protein called beta-amyloid in people who are at risk for developing Alzheimer's Disease (AD).

Detailed description: There is increasing evidence that nonsteroidal and cholesterol lowering medications may be associated with a delay in the onset of Alzheimer's disease (AD). There is separate evidence that beta-amyloid(1-42) is involved in the pathophysiology of AD and levels of beta-amyloid(1-42) in the cerebrospinal fluid (CSF) of AD patients are significantly lower than that found in controls. It has been suggested that these standard medications may have indirect effects that alter the normal course of AD, but there is no data to directly support this contention in humans. Based on previous work, it is our hypothesis that CSF beta-amyloid(1-42) levels may serve as an early biomarker of AD. Any pharmacological induced change in CSF beta-amyloid(1-42) might have profound implications for the eventual onset of illness. Therefore, the purpose of this study is to evaluate the short-term effects of two commonly prescribed nonsteroidal and cholesterol lowering medications, ibuprofen and lovastatin, on the levels of cerebrospinal fluid beta-amyloid(1-42) in a group of normal controls 'at risk' for developing AD.

Eligibility criteria: INCLUSION CRITERIA:

1. Normal volunteer over the age of 18
2. Cognitively within normal limits at baseline evaluation
3. Previously evaluated in Protocol 95-M-0096
4. Women of child-bearing potential will be advised not to become pregnant during the treatment period

EXCLUSION CRITERIA:

1. Known allergies to lovastatin or ibuprofen
2. Use of regular dosing of NSAID or statin during the previous month
3. Concurrent use of cyclosporine, itraconazole, ketoconazole, gemfibrozil, niacin, erythromycin, clarithromycin, HIV protease inhibitors or nefazodone because of possible drug interactions with lovastatin.
4. Women who are currently pregnant
5. Concurrent use of anticoagulants, aspirin, beta-adrenergic agents, cimetidine, digoxin and oral hypoglycemics because of possible drug interactions with ibuprofen.
6. Peptic ulcer disease by history
7. Autoimmune disease by history

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institute of Mental Health (NIMH)
state: Maryland
Study officials:
References:
citation: St George-Hyslop PH. Molecular genetics of Alzheimer's disease. Biol Psychiatry. 2000 Feb 1;47(3):183-99. doi: 10.1016/s0006-3223(99)00301-7.
citation: Small GW, Rabins PV, Barry PP, Buckholtz NS, DeKosky ST, Ferris SH, Finkel SI, Gwyther LP, Khachaturian ZS, Lebowitz BD, McRae TD, Morris JC, Oakley F, Schneider LS, Streim JE, Sunderland T, Teri LA, Tune LE. Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society. JAMA. 1997 Oct 22-29;278(16):1363-71.
citation: Bass MP, Yamaoka LH, Scott WK, Gaskell PC, Welsh-Bohmer KA, Roses AD, Saunders AM, Haines JL, Pericak-Vance MA. No association of alpha1-antichymotrypsin flanking region polymorphism and Alzheimer disease risk in early- and late-onset Alzheimer disease patients. Neurosci Lett. 1998 Jul 3;250(2):79-82. doi: 10.1016/s0304-3940(98)00398-x.