Ignite Creation Date:
2024-05-05 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00124397
Status:
COMPLETED
Last Update Posted:
2005-08-05
First Post:
2005-07-26
Brief Title:
Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus ATTEND-Study
Sponsor:
University of Southern Denmark
Organization:
University of Southern Denmark
Study Overview
Official Title:
Effect of High Dose Statin Therapy on Endothelial Function in Patients With Type 2 Diabetes Mellitus Without CAD
Status:
COMPLETED
Status Verified Date:
2005-07
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:
The aim of this study is to examine the effect of intensive cholesterol lowering therapy and tight blood pressure BP regulation on endothelial function inner cell layer of vessels that determines dilatation in type 2 diabetic patients without documented cardiovascular CV disease The hypothesis is that intensive cholesterol lowering and tight blood pressure regulation will due better than a control group
Detailed Description:
BackgroundThe prevalence of diagnosed type 2 diabetes mellitus DM is estimated to 2-4 in the general population in most European countries DM is associated with an increased frequency of manifest atherosclerotic disease Data from prospective studies demonstrate that the risk of developing acute coronary syndrome ACS in diabetic patients with no prior history of coronary artery disease CAD is equivalent to the risk observed in non-diabetics ACS survivors Most diabetic patients die from CAD Although DM is primarily a metabolic disorder it imposes a tremendous burden on macro- and micro-vessel diseaseThe important question of primary prevention of cardiovascular disease CVD in DM remains unanswered
In the major lipid-intervention studies where patients with CAD were included the subgroup with DM had at least as good effect of lipid lowering therapy with statins as non-diabetics The recently published Heart Protection Study supports the hypothesis of a favourable effect of statins in the primary prevention of CVD in DM The UK Prospective Diabetic Study has proved that tight blood pressure BP regulation reduces the frequency of micro- and macrovascular endpoint It has been suggested that combined lipid lowering with statins and tight BP regulation can have an additive effect in DM patients
It is well established that the atherosclerotic process has an impact on endothelial functionAn improvement of endothelial function by cholesterol lowering and BP reduction may serve as a surrogate endpoint for CAD
ObjectiveTo assess the effect of intensive lipid lowering on endothelial function in patients with DM and serum cholesterol level 65 mmoll and to evaluate the effect of combined lipid lowering and tight BP regulation on endothelial function in the same patient group
Methods This is a single-center randomised placebo-controlled study with three treatment arms Participants are blindly allocated to 1 atorvastatin 80 mg daily 2 corresponding placebo 3 open label treatment with atorvastatin 80 mg daily and tight BP regulation with 5-10 mg amlodipine 2-4 mg perindopril 4-8 mg doxazosin in mono- or combination therapy that aims BP 13080
Endothelial function is evaluated at baseline at 6 and 12 month non-invasively A high resolution ultrasound scan is performed on the right brachial artery to assess post ischemic flow mediated changes in arterial diameter Flow mediated dilatation FMD depends on an intact endothelium and is mediated via endogenous nitric oxid NO To test non-endothelium dependent vasodilatation 04 mg of sublingual nitroglycerin NG is administrated NG is a smooth muscle relaxant and acts as a source of NOThere is a well described relation tween endothelial function in the coronary arteries and in the brachial artery
Sample size the sample size in the study is based on the following assumptions
1 High resolution ultrasound technique has a high accuracy and reproducibility
2 The majority of the patients will have endothelial dysfunction
3 As shown in previous clinical studies an increase in FMD of 2 is significant at the 95 confidence interval
4 Patients randomised to atorvastatin will after one year treatment show an improvement of FMD of at leat 2 compared with the placebo group Patients treated openly with atorvastatin and BP regulation will have a further improvement of FMD of 2
Under these assumptions with a power of 80 and a 2 sided alfa of 5 a sample size of 160 patients are needed
In the major lipid-intervention studies where patients with CAD were included the subgroup with DM had at least as good effect of lipid lowering therapy with statins as non-diabetics The recently published Heart Protection Study supports the hypothesis of a favourable effect of statins in the primary prevention of CVD in DM The UK Prospective Diabetic Study has proved that tight blood pressure BP regulation reduces the frequency of micro- and macrovascular endpoint It has been suggested that combined lipid lowering with statins and tight BP regulation can have an additive effect in DM patients
It is well established that the atherosclerotic process has an impact on endothelial functionAn improvement of endothelial function by cholesterol lowering and BP reduction may serve as a surrogate endpoint for CAD
ObjectiveTo assess the effect of intensive lipid lowering on endothelial function in patients with DM and serum cholesterol level 65 mmoll and to evaluate the effect of combined lipid lowering and tight BP regulation on endothelial function in the same patient group
Methods This is a single-center randomised placebo-controlled study with three treatment arms Participants are blindly allocated to 1 atorvastatin 80 mg daily 2 corresponding placebo 3 open label treatment with atorvastatin 80 mg daily and tight BP regulation with 5-10 mg amlodipine 2-4 mg perindopril 4-8 mg doxazosin in mono- or combination therapy that aims BP 13080
Endothelial function is evaluated at baseline at 6 and 12 month non-invasively A high resolution ultrasound scan is performed on the right brachial artery to assess post ischemic flow mediated changes in arterial diameter Flow mediated dilatation FMD depends on an intact endothelium and is mediated via endogenous nitric oxid NO To test non-endothelium dependent vasodilatation 04 mg of sublingual nitroglycerin NG is administrated NG is a smooth muscle relaxant and acts as a source of NOThere is a well described relation tween endothelial function in the coronary arteries and in the brachial artery
Sample size the sample size in the study is based on the following assumptions
1 High resolution ultrasound technique has a high accuracy and reproducibility
2 The majority of the patients will have endothelial dysfunction
3 As shown in previous clinical studies an increase in FMD of 2 is significant at the 95 confidence interval
4 Patients randomised to atorvastatin will after one year treatment show an improvement of FMD of at leat 2 compared with the placebo group Patients treated openly with atorvastatin and BP regulation will have a further improvement of FMD of 2
Under these assumptions with a power of 80 and a 2 sided alfa of 5 a sample size of 160 patients are needed
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 |
|---|---|---|---|
| 2162 | None | None | None |