Vascular DiseaseNCT00293748
Effect of Atorvastatin (Lipitor) on Gene Expression in People With Vascular Disease
An observational study of Vascular Disease and Vascular Disease Risk, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will determine if the drug Atorvastatin (Lipitor) changes the genetic material found in blood cells of people with vascular (blood vessel) disease. Vascular diseases affect the blood flow in the body and can lead to a heart attack or stroke. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Vascular Disease, Vascular Disease Risk
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2006to 15 Dec 2008
- Phase
- Observational
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 21 or older
- Not taking a statin or other lipid-lowering drug and no history of statin use
- Two or more risk factors as listed below:
- Age (men greater than or equal to 45 years, women greater than or equal to 55 years)
- Hypertension (BP greater than or equal to 140/90 or on antihypertensive medication)
- Cigarette smoking
Show all 12Show fewer
- Coronary heart disease equivalents (includes diabetes mellitus, abdominal aortic aneurysm, peripheral vascular disease, carotid artery disease)
- Prior stroke or transient ischemic attack
- Family history of premature coronary heart disease (CHD): CHD in male first degree relative less than 55 years or CHD in female first degree relative less than 65 years
- Total cholesterol greater than or equal to 240mg/dL and/or LDL cholesterol greater than or equal to 160 mg/dL
- Low HDL cholesterol (less than 40 mg/dL)
- Note: A high HDL cholesterol (greater than 60 mg/dL) counts as a negative risk factor: its presence removes one risk factor from the total counts.
Who cannot join
- Current or past history of statin use
- Assessed need for immediate statin treatment by subject's primary care physician
- Current use of an investigational drug as part of another research protocol
- Chronic or active liver disease
- Chronic or active muscle disease
- Alcohol abuse
Show all 13Show fewer
- Prior myocardial infarct
- Heart failure
- Uncontrolled arrhythmias
- Any clinically important hematological or biochemical abnormality on routine screening
- Recent history of cancer
- Pregnant women or breast-feeding women
- Concomitant use of the following medications, including drugs that strongly inhibit CYP3A54: nicotinic acid, gemfibrozil, clofibrate, fenofibrate, verapamil, mibefradil, cyclcosporin, nefazodone, fluoxetine, paroxetine, ketoconazole, itraconazole, cimetadine, clarithromycin, erythromycin, protease inhibitors, NSAIDs, celebrex
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Dose-Response Study of Modulation of Gene Expression in Peripheral Blood Mononuclear Cells by Atorvastatin
This study will determine if the drug Atorvastatin (Lipitor) changes the genetic material found in blood cells of people with vascular (blood vessel) disease. Vascular diseases affect the blood flow in the body and can lead to a heart attack or stroke. Information gained from this study could be used to develop a more reliable blood test that predicts the risk of heart attack or stroke.
People 21 and older who have two or more risk factors for developing vascular disease are eligible for this study. Candidates are screened with a medical history, physical examination, electrocardiogram, ultrasound of the carotid (neck) arteries, blood tests, and check of blood pressure and heart rate.
Read more
Participants are randomly assigned to one of four treatment groups. Three groups receive Lipitor in a dose of either 10, 20 or 40 milligrams; the fourth group receives a placebo. All take the study drug for 3 months. In addition, they undergo the following tests and procedures:
Study Phase I (Months 2-4)
Participants in all groups are seen once a month at the NIH Clinical Center for blood tests and monitoring of drug side effects.
Study Phase 2 (Months 5-10)
- Placebo group: Participants are given 40 mg of Lipitor for 3 months (months 5-7) and seen by a physician once a month during that time. Blood is drawn at the 7-month visit and then participants are referred back to their physicians. During months 8, 9 and 10, participants are called once a month to check on their health. Participation ends after the tenth month.
- Lipitor group: Participants are referred back to their physicians for months 5 and 6 and are called once a month. During month 7, they return to the clinic for a follow-up evaluation and blood test. Participation ends after the seventh month.
Read the detailed description
Background: Atherosclerosis and its consequences - coronary heart disease and stroke - are principal causes of mortality in developed countries. Being able to accurately predict an individual's risk of vascular disease is needed for preventive strategies and measuring the effectiveness thereof. Current risk assessment tools are imperfect at best. It is possible that information from gene expression profiling of peripheral white blood cells may add predictive information about vascular risk. We previously identified a panel of 78 genes in the peripheral blood that correlated with an individual's future risk of stroke. We hypothesize that gene expression in white blood cells will be modified by an intervention that has been shown to reduce vascular risk via anti-inflammatory mechanisms: the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitor class of lipid lowering drugs, known as "statins". The vascular protective effects of statins appear to be due in part to immune modulation and to be dose-dependent. Statin administration has been shown to modulate gene expression in peripheral blood mononuclear cells in vitro.
Objectives: Overall: To determine if atorvastatin modulates gene expression in peripheral blood mononuclear cells in a dose dependent manner in a cohort of subjects at risk of vascular disease. Specific: To determine if: (1) Inflammatory genes are specifically and temporarily modified by atrovastatin in a dose dependent manner; (2) A previously defined panel of 78 genes is included among the genes modified by atorvastatin; and (3) Gene expression changes correlate the degree of gene expression modulation by atorvastatin with the degree of lipid lowering and other inflammatory parameters such as high sensitivity C-reactive protein.
Study Design: Dose-response randomized, blinded study of atorvastatin treatment of 120 volunteer subjects with at least two conventional vascular risk factors who are not currently taking a statin. In the first and primary phase of the study, subjects will be administered atorvastatin in a blinded fashion in one of four doses (0mg, 10mg, 20mg or 40mg) for a period of three months. Block randomization will stratify on age and risk factor status. In the second and validation phase of the study, the subjects randomized to 0mg of atorvastatin in phase 1 will receive 40mg of atorvastatin for a further 3 month period. The remaining subjects will not be randomized to study drug in phase II of the study. Lipid profiles, liver function tests and muscle enzymes will be measured prior to enrollment, and during the treatment phases of the study. Gene expression profiles in the peripheral blood will be measured using Affymetrix microarrays pre treatment and at the end of phases I and II.
Outcome measures: (1) Gene changes induced by statin treatment by dosage and over time; (2) Accuracy of vascular gene panel for defining gene expression changes induced by statin treatment; and (3) Correlations of gene expression changes with conventional vascular risk factors, changes in lipid and inflammatory markers and determination of best vascular risk prediction paradigm.
- Conditions
- Vascular Disease, Vascular Disease Risk
- Keywords
- Genomics, Statins, Coronary Heart Disease, Stroke, Inflammation, Gene Expression, Vascular Risk, Peripheral Blood Mononuclear Cells, Atorvastatin, Vascular Disease, Vascular Disease Risk
- Medical subject headings
- Vascular Diseases, Coronary Disease, Stroke, Inflammation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2006 (estimated)
- Study start13 Feb 2006
- Study completion15 Dec 2008
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 Vascular DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- 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
- Observational
- Enrolment
- 200 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00293748
- Sponsor's protocol ID
- 060097
- Other IDs
- 06-N-0097
- Status last verified
- 15 Dec 2008
- First submitted
- 17 Feb 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486-97. doi: 10.1001/jama.285.19.2486. No abstract available.
PubMed 11368702Altman DG, Bland JM. How to randomise. BMJ. 1999 Sep 11;319(7211):703-4. doi: 10.1136/bmj.319.7211.703. No abstract available.
PubMed 10480833Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J. 1991 Jan;121(1 Pt 2):293-8. doi: 10.1016/0002-8703(91)90861-b.
PubMed 1985385
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-Response Study of Modulation of Gene Expression in Peripheral Blood Mononuclear Cells by Atorvastatin
- ClinicalTrials.gov ID
- NCT00293748
- Acronym / sponsor ID
- 060097
- Conditions
- Vascular Disease, Vascular Disease Risk
- Keywords
- Genomics, Statins, Coronary Heart Disease, Stroke, Inflammation, Gene Expression, Vascular Risk, Peripheral Blood Mononuclear Cells
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 13 Feb 2006
- Study completion
- 15 Dec 2008
- First posted
- 17 Feb 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.
This study will determine if the drug Atorvastatin (Lipitor) changes the genetic material found in blood cells of people with vascular (blood vessel) disease. Vascular diseases affect the blood flow in the body and can lead to a heart attack or stroke. Information gained from this study could be used to develop a more reliable blood test that predicts the risk of heart attack or stroke.
People 21 and older who have two or more risk factors for developing vascular disease are eligible for this study. Candidates are screened with a medical history, physical examination, electrocardiogram, ultrasound of the carotid (neck) arteries, blood tests, and check of blood pressure and heart rate.
Participants are randomly assigned to one of four treatment groups. Three groups receive Lipitor in a dose of either 10, 20 or 40 milligrams; the fourth group receives a placebo. All take the study drug for 3 months. In addition, they undergo the following tests and procedures:
Study Phase I (Months 2-4)
Participants in all groups are seen once a month at the NIH Clinical Center for blood tests and monitoring of drug side effects.
Study Phase 2 (Months 5-10)
- Placebo group: Participants are given 40 mg of Lipitor for 3 months (months 5-7) and seen by a physician once a month during that time. Blood is drawn at the 7-month visit and then participants are referred back to their physicians. During months 8, 9 and 10, participants are called once a month to check on their health. Participation ends after the tenth month.
- Lipitor group: Participants are referred back to their physicians for months 5 and 6 and are called once a month. During month 7, they return to the clinic for a follow-up evaluation and blood test. Participation ends after the seventh month.
Detailed description
Background: Atherosclerosis and its consequences - coronary heart disease and stroke - are principal causes of mortality in developed countries. Being able to accurately predict an individual's risk of vascular disease is needed for preventive strategies and measuring the effectiveness thereof. Current risk assessment tools are imperfect at best. It is possible that information from gene expression profiling of peripheral white blood cells may add predictive information about vascular risk. We previously identified a panel of 78 genes in the peripheral blood that correlated with an individual's future risk of stroke. We hypothesize that gene expression in white blood cells will be modified by an intervention that has been shown to reduce vascular risk via anti-inflammatory mechanisms: the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitor class of lipid lowering drugs, known as "statins". The vascular protective effects of statins appear to be due in part to immune modulation and to be dose-dependent. Statin administration has been shown to modulate gene expression in peripheral blood mononuclear cells in vitro.
Objectives: Overall: To determine if atorvastatin modulates gene expression in peripheral blood mononuclear cells in a dose dependent manner in a cohort of subjects at risk of vascular disease. Specific: To determine if: (1) Inflammatory genes are specifically and temporarily modified by atrovastatin in a dose dependent manner; (2) A previously defined panel of 78 genes is included among the genes modified by atorvastatin; and (3) Gene expression changes correlate the degree of gene expression modulation by atorvastatin with the degree of lipid lowering and other inflammatory parameters such as high sensitivity C-reactive protein.
Study Design: Dose-response randomized, blinded study of atorvastatin treatment of 120 volunteer subjects with at least two conventional vascular risk factors who are not currently taking a statin. In the first and primary phase of the study, subjects will be administered atorvastatin in a blinded fashion in one of four doses (0mg, 10mg, 20mg or 40mg) for a period of three months. Block randomization will stratify on age and risk factor status. In the second and validation phase of the study, the subjects randomized to 0mg of atorvastatin in phase 1 will receive 40mg of atorvastatin for a further 3 month period. The remaining subjects will not be randomized to study drug in phase II of the study. Lipid profiles, liver function tests and muscle enzymes will be measured prior to enrollment, and during the treatment phases of the study. Gene expression profiles in the peripheral blood will be measured using Affymetrix microarrays pre treatment and at the end of phases I and II.
Outcome measures: (1) Gene changes induced by statin treatment by dosage and over time; (2) Accuracy of vascular gene panel for defining gene expression changes induced by statin treatment; and (3) Correlations of gene expression changes with conventional vascular risk factors, changes in lipid and inflammatory markers and determination of best vascular risk prediction paradigm.
Study design
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age 21 or older
- Not taking a statin or other lipid-lowering drug and no history of statin use
- Two or more risk factors as listed below:
- Age (men greater than or equal to 45 years, women greater than or equal to 55 years)
- Hypertension (BP greater than or equal to 140/90 or on antihypertensive medication)
Key exclusion criteria (13 listed)
- Current or past history of statin use
- Assessed need for immediate statin treatment by subject's primary care physician
- Current use of an investigational drug as part of another research protocol
- Chronic or active liver disease
- Chronic or active muscle disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 11368702Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486-97. doi: 10.1001/jama.285.19.2486. No abstract available.
- Background: PubMed 10480833Altman DG, Bland JM. How to randomise. BMJ. 1999 Sep 11;319(7211):703-4. doi: 10.1136/bmj.319.7211.703. No abstract available.
- Background: PubMed 1985385Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J. 1991 Jan;121(1 Pt 2):293-8. doi: 10.1016/0002-8703(91)90861-b.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Vascular Disease and Vascular Disease Risk, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 12 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 2 Jul 2017. 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.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00293748, 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 2 Jul 2017.