Ignite Creation Date:
2024-05-05 @ 4:40 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00293748
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2006-02-17
Brief Title:
Effect of Atorvastatin Lipitor on Gene Expression in People With Vascular Disease
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Dose-Response Study of Modulation of Gene Expression in Peripheral Blood Mononuclear Cells by Atorvastatin
Status:
COMPLETED
Status Verified Date:
2008-12-15
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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 individuals 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 individuals 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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-N-0097 | None | None | None |