Alzheimer's DiseasePhase 4NCT00303277
Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
A Phase 4 study testing simvastatin and pravastatin in people with Alzheimer's Disease and Aging, run by Seattle Institute for Biomedical and Clinical Research at 1 site in United States.
Trial summary
Recent evidence suggests that there is a significant overlap between AD and cerebrovascular disease. In fact, AD and cerebrovascular disease may share some of the same risk factors, including hypercholesterolemia. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Alzheimer's Disease, Aging
- What is being tested?
- simvastatin and pravastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2002to Apr 2005
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Total cholesterol > 200, and/or LDL > 130
- No cognitive impairment
- Statin-naive for at least one year
- Women must not be pregnant, nursing, or planning to become pregnant
Who cannot join
- Back ailments which would hinder LP procedure
- Neurological disease, including stroke, Parkinson's disease, Multiple Sclerosis, uncontrolled epilepsy, history of severe head trauma
- Hepatic disease
- Renal insufficiency
- Unstable medical disease
- Severe pulmonary disease
Show all 13Show fewer
- Severe cardiac disease
- Uncontrolled hypertension (greater than 160/90)
- Uncontrolled hyper/hypothyroidism
- History of blood clotting abnormalities or platelet abnormalities
- History of chronic major psychiatric disorders or presence of current major depressive disorder (by DSM-IV criteria)
- History of substance abuse within the past year
- Taking exclusionary medications
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Puget Sound Health Care System
Seattle, Washington, 98108
About this study
Recent evidence suggests that there is a significant overlap between AD and cerebrovascular disease. In fact, AD and cerebrovascular disease may share some of the same risk factors, including hypercholesterolemia. In addition, studies have suggested that the HMG Co-A reductase inhibitor lipid-lowering agents, known as "statins," decrease the risk of AD by up to 70%; however, effects differed by specific statin use. This study will compare two statins, simvastatin (which crosses the blood brain barrier) and pravastatin (which does not), with respect to their ability to alter blood and cerebrospinal fluid (CSF) levels of AD and inflammatory markers. The primary aim of the proposed study is to determine whether there is a reduction in Abeta with statins and whether the ability of the statin to cross the blood-brain barrier will affect its ability to decrease Abeta. If it can be demonstrated that statins alter AD-associated biomarkers, this would have broad implications for the treatment and prevention of AD.
Read the detailed description
Recent evidence suggests that there is a significant overlap between AD and cerebrovascular disease. In fact, AD and cerebrovascular disease may share some of the same risk factors, including hypercholesterolemia. In addition, studies have suggested that the HMG Co-A reductase inhibitor lipid-lowering agents, known as "statins," decrease the risk of AD by up to 70%; however, effects differed by specific statin use. This study will compare two statins, simvastatin (which crosses the blood brain barrier) and pravastatin (which does not), with respect to their ability to alter blood and cerebrospinal fluid (CSF) levels of AD and inflammatory markers. The primary aim of the proposed study is to determine whether there is a reduction in Abeta with statins and whether the lipophilicity of the statin will affect its ability to decrease Abeta. In addition, the proposal will determine statin effects on both peripheral and central inflammation and whether the lipophilicity of the statin will affect its ability to decrease inflammation. If it can be demonstrated that statins alter AD-associated biomarkers, this would have broad implications for the treatment and prevention of AD.
This study will be performed in 60 cognitively normal middle-aged and older persons with hypercholesterolemia (total cholesterol >200 and/or LDL>130), presumably persons that have a lipid-related increased risk of AD and in whom alterations of CSF Abeta can be interpreted.The differential effects of the two statins will be evaluated in a 12-week randomized treatment trial with 30 subjects in each group.
Prior to randomization and following 12 weeks of treatment with simvastatin or pravastatin, subjects will undergo CSF and blood collection. In the CSF, concentrations of Abeta 1-40, Abeta 1-42, soluble APP, tau, 24S-hydroxycholesterol, apoE, total cholesterol, F2-isoprostanes, glucose, protein, and cell count will be measured. In the blood, concentrations of total cholesterol, HDL, LDL, triglyceride, phospholipids, fatty acids, 24S-hydroxycholesterol, apoE, apoB, apoA1, Abeta 1-40, Abeta 1-42, F2-isoprostanes, C-reactive protein, fibrinogen, iron, homocysteine, and albumin will be measured. Plasma simvastatin and pravastatin concentrations will be measured at study completion. APOE genotyping will be performed.
- Conditions
- Alzheimer's Disease, Aging
- Being tested
- simvastatin, pravastatin
- Keywords
- Alzheimer's disease, beta-amyloid, statins
- Medical subject headings
- Alzheimer Disease, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
simvastatinDrug
Also called Zocor
simvastatin 40 mg tablets once per day for 12 weeks
pravastatinDrug
Also called Lipitor
pravastatin 80 mg tablets once per day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | simvastatin Receives: Drug: simvastatin |
| 2 | Active comparator | pravastatin Receives: Drug: pravastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
CSF abeta levels
Measured: baseline and 12 weeks
Secondary outcomes (1)
CSF biomarkers
Measured: baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2006 (estimated)
- Study startAug 2002
- Primary completionApr 2005
- Study completionApr 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Institute for Biomedical and Clinical Research
- Sponsor type
- University, hospital or other
- Investigators
- Elaine R Peskind, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00303277
- Sponsor's protocol ID
- 21974
- Status last verified
- Apr 2010
- First submitted
- 14 Mar 2006
- Last updated
- 13 Apr 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Li G, Larson EB, Sonnen JA, Shofer JB, Petrie EC, Schantz A, Peskind ER, Raskind MA, Breitner JC, Montine TJ. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology. 2007 Aug 28;69(9):878-85. doi: 10.1212/01.wnl.0000277657.95487.1c.
PubMed 17724290Li G, Higdon R, Kukull WA, Peskind E, Van Valen Moore K, Tsuang D, van Belle G, McCormick W, Bowen JD, Teri L, Schellenberg GD, Larson EB. Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neurology. 2004 Nov 9;63(9):1624-8. doi: 10.1212/01.wnl.0000142963.90204.58.
PubMed 15534246Riekse RG, Li G, Petrie EC, Leverenz JB, Vavrek D, Vuletic S, Albers JJ, Montine TJ, Lee VM, Lee M, Seubert P, Galasko D, Schellenberg GD, Hazzard WR, Peskind ER. Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid. J Alzheimers Dis. 2006 Dec;10(4):399-406. doi: 10.3233/jad-2006-10408.
PubMed 17183151
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
- ClinicalTrials.gov ID
- NCT00303277
- Acronym / sponsor ID
- 21974
- Conditions
- Alzheimer's Disease, Aging
- Keywords
- Alzheimer's disease, beta-amyloid, statins
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Seattle Institute for Biomedical and Clinical ResearchUniversity, hospital or other
- Study start
- Aug 2002
- Primary completion
- Apr 2005 (actual)
- Study completion
- Apr 2005 (actual)
- First posted
- 16 Mar 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent evidence suggests that there is a significant overlap between AD and cerebrovascular disease. In fact, AD and cerebrovascular disease may share some of the same risk factors, including hypercholesterolemia. In addition, studies have suggested that the HMG Co-A reductase inhibitor lipid-lowering agents, known as "statins," decrease the risk of AD by up to 70%; however, effects differed by specific statin use. This study will compare two statins, simvastatin (which crosses the blood brain barrier) and pravastatin (which does not), with respect to their ability to alter blood and cerebrospinal fluid (CSF) levels of AD and inflammatory markers. The primary aim of the proposed study is to determine whether there is a reduction in Abeta with statins and whether the ability of the statin to cross the blood-brain barrier will affect its ability to decrease Abeta. If it can be demonstrated that statins alter AD-associated biomarkers, this would have broad implications for the treatment and prevention of AD.
Detailed description
Recent evidence suggests that there is a significant overlap between AD and cerebrovascular disease. In fact, AD and cerebrovascular disease may share some of the same risk factors, including hypercholesterolemia. In addition, studies have suggested that the HMG Co-A reductase inhibitor lipid-lowering agents, known as "statins," decrease the risk of AD by up to 70%; however, effects differed by specific statin use. This study will compare two statins, simvastatin (which crosses the blood brain barrier) and pravastatin (which does not), with respect to their ability to alter blood and cerebrospinal fluid (CSF) levels of AD and inflammatory markers. The primary aim of the proposed study is to determine whether there is a reduction in Abeta with statins and whether the lipophilicity of the statin will affect its ability to decrease Abeta. In addition, the proposal will determine statin effects on both peripheral and central inflammation and whether the lipophilicity of the statin will affect its ability to decrease inflammation. If it can be demonstrated that statins alter AD-associated biomarkers, this would have broad implications for the treatment and prevention of AD.
This study will be performed in 60 cognitively normal middle-aged and older persons with hypercholesterolemia (total cholesterol >200 and/or LDL>130), presumably persons that have a lipid-related increased risk of AD and in whom alterations of CSF Abeta can be interpreted.The differential effects of the two statins will be evaluated in a 12-week randomized treatment trial with 30 subjects in each group.
Prior to randomization and following 12 weeks of treatment with simvastatin or pravastatin, subjects will undergo CSF and blood collection. In the CSF, concentrations of Abeta 1-40, Abeta 1-42, soluble APP, tau, 24S-hydroxycholesterol, apoE, total cholesterol, F2-isoprostanes, glucose, protein, and cell count will be measured. In the blood, concentrations of total cholesterol, HDL, LDL, triglyceride, phospholipids, fatty acids, 24S-hydroxycholesterol, apoE, apoB, apoA1, Abeta 1-40, Abeta 1-42, F2-isoprostanes, C-reactive protein, fibrinogen, iron, homocysteine, and albumin will be measured. Plasma simvastatin and pravastatin concentrations will be measured at study completion. APOE genotyping will be performed.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: simvastatinsimvastatin |
| 2 | Active comparator | Drug: pravastatinpravastatin |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Total cholesterol > 200, and/or LDL > 130
- No cognitive impairment
- Statin-naive for at least one year
- Women must not be pregnant, nursing, or planning to become pregnant
Key exclusion criteria (13 listed)
- Back ailments which would hinder LP procedure
- Neurological disease, including stroke, Parkinson's disease, Multiple Sclerosis, uncontrolled epilepsy, history of severe head trauma
- Hepatic disease
- Renal insufficiency
- Unstable medical disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| simvastatinAlso: Zocorsimvastatin 40 mg tablets once per day for 12 weeks | Drug | 1 |
| pravastatinAlso: Lipitorpravastatin 80 mg tablets once per day for 12 weeks | Drug | 2 |
Primary outcome
CSF abeta levels
Time frame: baseline and 12 weeks
1 secondary outcome
CSF biomarkers
Time frame: baseline and 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2010.
- Background: PubMed 17724290Li G, Larson EB, Sonnen JA, Shofer JB, Petrie EC, Schantz A, Peskind ER, Raskind MA, Breitner JC, Montine TJ. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology. 2007 Aug 28;69(9):878-85. doi: 10.1212/01.wnl.0000277657.95487.1c.
- Background: PubMed 15534246Li G, Higdon R, Kukull WA, Peskind E, Van Valen Moore K, Tsuang D, van Belle G, McCormick W, Bowen JD, Teri L, Schellenberg GD, Larson EB. Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neurology. 2004 Nov 9;63(9):1624-8. doi: 10.1212/01.wnl.0000142963.90204.58.
- Results publication: PubMed 17183151Riekse RG, Li G, Petrie EC, Leverenz JB, Vavrek D, Vuletic S, Albers JJ, Montine TJ, Lee VM, Lee M, Seubert P, Galasko D, Schellenberg GD, Hazzard WR, Peskind ER. Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid. J Alzheimers Dis. 2006 Dec;10(4):399-406. doi: 10.3233/jad-2006-10408.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elaine R Peskind, MD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing simvastatin and pravastatin in people with Alzheimer's Disease and Aging, run by Seattle Institute for Biomedical and Clinical Research at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CSF abeta levels (time frame: baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00303277, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2010.