Ignite Creation Date:
2024-05-05 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00150722
Status:
COMPLETED
Last Update Posted:
2008-11-10
First Post:
2005-09-06
Brief Title:
High-Density Lipoprotein HDL Modulation and Endothelial Function
Sponsor:
University of Calgary
Organization:
University of Calgary
Study Overview
Official Title:
HDL Modulation and Endothelial Function
Status:
COMPLETED
Status Verified Date:
2008-11
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:
It is well known that lowering low-density lipoprotein LDL bad cholesterol is beneficial for decreasing heart attacks and death More recently focus has been on trying to raise HDL good cholesterol The purpose of the present study is to determine if the addition of a sustained release preparation of niacin Niaspan - a medicine to raise HDL cholesterol to LDL lowering with a statin type medication results in improved vascular health The study of the well being of ones vessel wall endothelial function will serve as a marker of treatment effect in the study
Hypotheses Extended-release ER niacin will improve endothelial function measured as brachial flow-mediated dilation FMD - 10 end-point and as pulse volume amplitude by pulse arterial tonometry PAT 20 end-point in subjects with established atherosclerosis whose LDL cholesterol is optimally treated with statin therapy
Hypotheses Extended-release ER niacin will improve endothelial function measured as brachial flow-mediated dilation FMD - 10 end-point and as pulse volume amplitude by pulse arterial tonometry PAT 20 end-point in subjects with established atherosclerosis whose LDL cholesterol is optimally treated with statin therapy
Detailed Description:
Purpose To determine the incremental value of extended-release ER niacin in combination with high dose statin therapy on brachial endothelial function in subjects with coronary atherosclerosis
Hypotheses
1 ER niacin will improve endothelial function measured as brachial flow-mediated dilation FMD - primary end-point hyperemic velocity and as pulse volume amplitude by PAT 20 end-point in subjects with established atherosclerosis whose LDL cholesterol is optimally treated with statin therapy
2 Hyperemic pulse volume amplitude in the finger assessed by pulse arterial tonometry PAT will correlate with brachial FMD as assessed by high resolution ultrasound of the brachial artery
Background In patients with established coronary atherosclerosis secondary prevention strategies with lipid lowering agents have resulted in event reductions of 25-30 Despite aggressive cholesterol lowering with statins event rates remain 2-3 per year for subjects at high risk While many new therapeutic targets have been suggested recently there has been much interest in modulation of HDL cholesterol Low HDL is a powerful risk factor for coronary events HDL functions in the reverse cholesterol transport system to remove excess cholesterol from tissues including the vessel wall In addition HDL has other vascular benefits including anti-oxidant and direct endothelial effects The most effective available way to modulate HDL is with niacin An ER formulation of niacin Niaspan - Kos will be available in Canada in 2005 and has been shown to be efficacious and safe
The endothelium plays a key role in vascular homeostasis through the release of paracrine factors such as nitric oxide Dysfunction of the endothelium occurs in response to risk factors and atherosclerosis Endothelial function can be readily measured non-invasively in humans and pharmacotherapy that has been shown to reduce cardiovascular events improves endothelium-dependent vasodilation In addition recent studies have suggested that measures of endothelial function have prognostic implications for subjects at risk for vascular events As such the measurement of endothelial function has become well established as a surrogate marker of disease activity and will be utilized in the current study The effect of niacin on endothelial function has not been studied
Design The study is a single center randomized placebo controlled cross-over design An open label one month run in phase of atorvastatin therapy will be utilized to establish baseline endothelial function and ensure tolerability of the atorvastatin Brachial ultrasound determination of FMD and pulse arterial tonometry PAT will be utilized Open label atorvastatin will be continued throughout the study in all subjects Following baseline measurements of endothelial function patients will be randomized to placebo or escalating doses of ER niacin for a treatment phase of 3 months At this point repeat measurements will be undertaken and subjects will cross-over to the alternate therapy for an additional 3 months followed by final measurements The use of different methods of endothelial function measurement will allow a comparison of the two
Subjects will have established coronary atherosclerosis and an HDL 11 mmolL and be at least one month post percutaneous coronary intervention PCI or 3 months post coronary artery bypass graft CABG Exclusion criteria include active gout gallbladder or peptic ulcer disease change of endothelial modulating drugs within one month of study initiation or use of niacin
The primary end-point of the study is brachial artery flow-mediated vasodilation The primary efficacy analysis will be a comparison of the change in FMD during active ER niacin treatment compared with baseline The sample size is based on an expected 2 difference in FMD SD 5 p 005 and power of 80
Significance Despite the reduction of mortality with current LDL lowering approaches morbidity and mortality remain unacceptably high HDL has recently gained favor as a therapeutic target to lower cardiovascular event rates The current study will evaluate the effect of HDL raising on endothelial health a surrogate marker of atherosclerosis activity
Hypotheses
1 ER niacin will improve endothelial function measured as brachial flow-mediated dilation FMD - primary end-point hyperemic velocity and as pulse volume amplitude by PAT 20 end-point in subjects with established atherosclerosis whose LDL cholesterol is optimally treated with statin therapy
2 Hyperemic pulse volume amplitude in the finger assessed by pulse arterial tonometry PAT will correlate with brachial FMD as assessed by high resolution ultrasound of the brachial artery
Background In patients with established coronary atherosclerosis secondary prevention strategies with lipid lowering agents have resulted in event reductions of 25-30 Despite aggressive cholesterol lowering with statins event rates remain 2-3 per year for subjects at high risk While many new therapeutic targets have been suggested recently there has been much interest in modulation of HDL cholesterol Low HDL is a powerful risk factor for coronary events HDL functions in the reverse cholesterol transport system to remove excess cholesterol from tissues including the vessel wall In addition HDL has other vascular benefits including anti-oxidant and direct endothelial effects The most effective available way to modulate HDL is with niacin An ER formulation of niacin Niaspan - Kos will be available in Canada in 2005 and has been shown to be efficacious and safe
The endothelium plays a key role in vascular homeostasis through the release of paracrine factors such as nitric oxide Dysfunction of the endothelium occurs in response to risk factors and atherosclerosis Endothelial function can be readily measured non-invasively in humans and pharmacotherapy that has been shown to reduce cardiovascular events improves endothelium-dependent vasodilation In addition recent studies have suggested that measures of endothelial function have prognostic implications for subjects at risk for vascular events As such the measurement of endothelial function has become well established as a surrogate marker of disease activity and will be utilized in the current study The effect of niacin on endothelial function has not been studied
Design The study is a single center randomized placebo controlled cross-over design An open label one month run in phase of atorvastatin therapy will be utilized to establish baseline endothelial function and ensure tolerability of the atorvastatin Brachial ultrasound determination of FMD and pulse arterial tonometry PAT will be utilized Open label atorvastatin will be continued throughout the study in all subjects Following baseline measurements of endothelial function patients will be randomized to placebo or escalating doses of ER niacin for a treatment phase of 3 months At this point repeat measurements will be undertaken and subjects will cross-over to the alternate therapy for an additional 3 months followed by final measurements The use of different methods of endothelial function measurement will allow a comparison of the two
Subjects will have established coronary atherosclerosis and an HDL 11 mmolL and be at least one month post percutaneous coronary intervention PCI or 3 months post coronary artery bypass graft CABG Exclusion criteria include active gout gallbladder or peptic ulcer disease change of endothelial modulating drugs within one month of study initiation or use of niacin
The primary end-point of the study is brachial artery flow-mediated vasodilation The primary efficacy analysis will be a comparison of the change in FMD during active ER niacin treatment compared with baseline The sample size is based on an expected 2 difference in FMD SD 5 p 005 and power of 80
Significance Despite the reduction of mortality with current LDL lowering approaches morbidity and mortality remain unacceptably high HDL has recently gained favor as a therapeutic target to lower cardiovascular event rates The current study will evaluate the effect of HDL raising on endothelial health a surrogate marker of atherosclerosis activity
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 |
|---|---|---|---|
| Heart and Stroke Foundation | None | None | None |