Ignite Creation Date:
2024-05-06 @ 9:35 AM
Last Modification Date:
2024-10-26 @ 12:16 PM
Study NCT ID:
NCT03011775
Status:
COMPLETED
Last Update Posted:
2022-03-10
First Post:
2016-12-29
Brief Title:
Effect of Pioglitazone on Insulin Resistance Atherosclerosis Progression and Clinical Course of Coronary Heart Disease
Sponsor:
Ukrainian Medical Stomatological Academy
Organization:
Ukrainian Medical Stomatological Academy
Study Overview
Official Title:
Effect of Pioglitazone on Insulin Resistance Progression of Atherosclerosis and Clinical Course of Coronary Heart Disease
Status:
COMPLETED
Status Verified Date:
2022-01
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:
EFFORT
Brief Summary:
Pioglitazone a medication of thiazolidinedione group is capable of triggering the peroxisome proliferator-activated receptors PPAR-γ Activation of receptor PPAR-γ regulates carbohydrate and lipid metabolism immune and inflammatory responses in heart tissues
Our aim will to study the effect of pioglitazone on insulin resistance the clinical course of atherosclerosis and coronary heart disease CHD
The study will include 43 patients with coronary artery disease Patients will be divided into the study group - 20 patients in whom pioglitazone will be included in the combined therapy at a dose of 15 mg 1 time per day in the morning and the control group - 23 patients receiving standard complex drug therapy over 6 months Patients will be underwent clinical examination ultrasound of neck vessels study of carbohydrate and lipid metabolism
The end primary points of the study will be the onset of death due to myocardial infarction coronary revascularization procedures coronary artery bypass grafting CABG or percutaneous coronary intervention PCI or hospitalization for acute coronary syndrome ACS or unstable angina UA
Predefined secondary end points included carotic atherosclerotic leisure carotic intima-media thickness diameter of stenosis presents of atherosclerotic plaque systemic inflammation level the level of C reactive protein lipid metabolism levels of serum total cholesterol triglycerides high and low density lipoproteins level of insulin resistance oral glucose tolerance test blood glucose
Our aim will to study the effect of pioglitazone on insulin resistance the clinical course of atherosclerosis and coronary heart disease CHD
The study will include 43 patients with coronary artery disease Patients will be divided into the study group - 20 patients in whom pioglitazone will be included in the combined therapy at a dose of 15 mg 1 time per day in the morning and the control group - 23 patients receiving standard complex drug therapy over 6 months Patients will be underwent clinical examination ultrasound of neck vessels study of carbohydrate and lipid metabolism
The end primary points of the study will be the onset of death due to myocardial infarction coronary revascularization procedures coronary artery bypass grafting CABG or percutaneous coronary intervention PCI or hospitalization for acute coronary syndrome ACS or unstable angina UA
Predefined secondary end points included carotic atherosclerotic leisure carotic intima-media thickness diameter of stenosis presents of atherosclerotic plaque systemic inflammation level the level of C reactive protein lipid metabolism levels of serum total cholesterol triglycerides high and low density lipoproteins level of insulin resistance oral glucose tolerance test blood glucose
Detailed Description:
The study will include 43 people aged between 45 and 68 who suffered from ischemic heart disease Before starting the study all participants will give written informed consent will be obtained of the Commission on Bioethics at Ukrainian Medical Stomatological Academy Inclusion criteria will be as follows stable exertional angina type 2 diabetes mellitus DM without receiving injectable antidiabetic drugs Exclusion criteria will be the presence of myocardial infarction history intervention malignant arterial hypertension AH chronic heart failure HF of III-IV functional class FC systemic connective tissue diseases cancer and oncohematological diseases severe infectious diseases chronic inflammatory diseases history of acute cerebrovascular accidents disorders of cardiac rhythm by atrial fibrillation type The end study will be the primary points the onset of death due to myocardial infarction coronary revascularization procedures coronary artery bypass grafting CABG or percutaneous coronary intervention PCI or hospitalization for acute coronary syndrome ACS or unstable angina UA
The diagnosis of CHD in patients will confirmed by the presence of FC I-III angina according to the classification of the Canadian Cardiovascular Society and the phenomena of circulatory insufficiency according to the classification of New York Heart Association NYHA Bicycle ergometry will perform on Veloergotest 05 Ukraine via step increasing loading capacity with a consequent increase under control of electrocardiogram ECG and BP The force of step I will be 150 kgm min 25 W II - 300 kgm min 50 W III - 450 kgm min 75 W IV - 600 kgm min 100 W V - 750 kgm min 125 W VI - 900 kgm min 150 W the duration of each step was 3 minutes Tolerance of CHD patients to exercise will calculate from the value of the threshold load capacity and volume of work performed The threshold load capacity of 150 kgm min 25 W was considered very low and consistent with angina FC IV 300 kgm min 50 W - low FC III 450-600 kgm min 75-100 W - average FC II 750 kgm min 125 W and above - high exercise capacity FC I The criteria will cease bicycle ergometry termination conventional clinical or ECG signs of myocardial ischemia
Prior to inclusion in the clinical trial all patients will receive conventional treatment and will screening examination to verify the diagnosis of coronary heart disease and type 2 diabetes
After screening we will selected 43 patients who received standard medical therapy complex isosorbide dinitrate 10-20 mg 2 times a day acetylsalicylic acid 75 mg 1 time a day bisoprolol 25 mg 1 time a day rosuvastatin 20 mg 1 time a day ramipril 5 mg 1 time a day Patients also will receive recommendations on diet and lifestyle changes Patients will receive the conventional treatment for at least one month to achieve stable parameters
On the first day of the study blood samples will take from all patients clinical examination was conducted After clinical and laboratory studies patients will randomized by gender age and severity of clinical manifestations of coronary heart disease As a result of randomization patients will divide into the study group n 20 and control group n 23 The complex therapy of the study group will include pioglitazone 15 mg 1 time per day in the morning Pioglar Ranbaxy India for 6 months Patients of the control group will continue to receive only a standard set of drug therapy Re-examination will carry out in 6 months
The examination will include the collection of medical history and objective data gender age overweight and obesity hypertension type 2 diabetes Patients will evaluate by anthropometric indicators height weight body mass index BMI blood pressure - systolic and diastolic SBP and DBP heart rate HR will measure ECG will register
In order to determine the status of vascular bed patients will underwent ultrasonography US of neck vessels on ULTIMA PA sensor L5 - 1240 in accordance with standard protocols in B-mode on the three levels of vascular bed and bilaterally at the end of diastole in the proximal medial and distal points at a distance of 1 cm from the bifurcation of the posterior wall of the right and left common carotid artery RCCA and LCCA respectively as more distant from the transducer unit Contour of the carotid arteries will register their inner lumen indicators for ASP presence size localization will record as well as IMT of the carotid arteries IMT will measure as the distance between the first and the second echogenic lines of located site according to the procedure Pignoli P et al The diameter of RCCA LCCA and the internal carotid artery ICA will assess at the end of systole and diastole as the distance between the IMT Normal IMT will consider less than 09 mm CCA IMT 14 mm was evaluated as ASP and in the range of 10-13 mm as the thickening of IMT ESH ESC 2007 The standard criteria for the diagnosis of hemodynamically significant stenosis are the narrowing of the arterial lumen by more than 50
The volume of laboratory tests will includ general clinical and biochemical blood analysis For the control of carbohydrate metabolism glycemic profiles will study determining fasting glucose and after 1 hour after taking 75 g of glucose oral glucose tolerance test OGTT via glucose oxidase method hyperglycemic factor will calculate In all patients lipid profile will studied total cholesterol TC triglycerides TG and cholesterol of high-density lipoproteins HDL Diakon-DS Russia content of cholesterol in low-density lipoproteins LDL and very low density lipoproteins VLDL will calculate as well as atherogenic factor AF Study of the inflammatory response will conduct by determining the concentration of basic biomarkers - high-sensitivity C-reactive protein hs-CRP DRG USA human tissue inhibitor of metalloproteinase-1 TIMP-1 eBioscience Austria according to the manufacturers protocols of test systems via immunoenzyme method The presence of microalbuminuria will determine using test strips Mikroalbufan Lachema Czech Republic the ratio albumin creatinine in urine will calculated
Statistical processing will perform using software Statistica 60 StatSoft USA with calculation of average M and standard error of the average m Methods of descriptive statistics will use comparison of performance in groups will perform by parametric Students t-test and non-parametric Pearson χ2 test Fishers exact test Mann-Whitney test statistics For all types of analysis the differences at p 005 will consider statistically significant
The diagnosis of CHD in patients will confirmed by the presence of FC I-III angina according to the classification of the Canadian Cardiovascular Society and the phenomena of circulatory insufficiency according to the classification of New York Heart Association NYHA Bicycle ergometry will perform on Veloergotest 05 Ukraine via step increasing loading capacity with a consequent increase under control of electrocardiogram ECG and BP The force of step I will be 150 kgm min 25 W II - 300 kgm min 50 W III - 450 kgm min 75 W IV - 600 kgm min 100 W V - 750 kgm min 125 W VI - 900 kgm min 150 W the duration of each step was 3 minutes Tolerance of CHD patients to exercise will calculate from the value of the threshold load capacity and volume of work performed The threshold load capacity of 150 kgm min 25 W was considered very low and consistent with angina FC IV 300 kgm min 50 W - low FC III 450-600 kgm min 75-100 W - average FC II 750 kgm min 125 W and above - high exercise capacity FC I The criteria will cease bicycle ergometry termination conventional clinical or ECG signs of myocardial ischemia
Prior to inclusion in the clinical trial all patients will receive conventional treatment and will screening examination to verify the diagnosis of coronary heart disease and type 2 diabetes
After screening we will selected 43 patients who received standard medical therapy complex isosorbide dinitrate 10-20 mg 2 times a day acetylsalicylic acid 75 mg 1 time a day bisoprolol 25 mg 1 time a day rosuvastatin 20 mg 1 time a day ramipril 5 mg 1 time a day Patients also will receive recommendations on diet and lifestyle changes Patients will receive the conventional treatment for at least one month to achieve stable parameters
On the first day of the study blood samples will take from all patients clinical examination was conducted After clinical and laboratory studies patients will randomized by gender age and severity of clinical manifestations of coronary heart disease As a result of randomization patients will divide into the study group n 20 and control group n 23 The complex therapy of the study group will include pioglitazone 15 mg 1 time per day in the morning Pioglar Ranbaxy India for 6 months Patients of the control group will continue to receive only a standard set of drug therapy Re-examination will carry out in 6 months
The examination will include the collection of medical history and objective data gender age overweight and obesity hypertension type 2 diabetes Patients will evaluate by anthropometric indicators height weight body mass index BMI blood pressure - systolic and diastolic SBP and DBP heart rate HR will measure ECG will register
In order to determine the status of vascular bed patients will underwent ultrasonography US of neck vessels on ULTIMA PA sensor L5 - 1240 in accordance with standard protocols in B-mode on the three levels of vascular bed and bilaterally at the end of diastole in the proximal medial and distal points at a distance of 1 cm from the bifurcation of the posterior wall of the right and left common carotid artery RCCA and LCCA respectively as more distant from the transducer unit Contour of the carotid arteries will register their inner lumen indicators for ASP presence size localization will record as well as IMT of the carotid arteries IMT will measure as the distance between the first and the second echogenic lines of located site according to the procedure Pignoli P et al The diameter of RCCA LCCA and the internal carotid artery ICA will assess at the end of systole and diastole as the distance between the IMT Normal IMT will consider less than 09 mm CCA IMT 14 mm was evaluated as ASP and in the range of 10-13 mm as the thickening of IMT ESH ESC 2007 The standard criteria for the diagnosis of hemodynamically significant stenosis are the narrowing of the arterial lumen by more than 50
The volume of laboratory tests will includ general clinical and biochemical blood analysis For the control of carbohydrate metabolism glycemic profiles will study determining fasting glucose and after 1 hour after taking 75 g of glucose oral glucose tolerance test OGTT via glucose oxidase method hyperglycemic factor will calculate In all patients lipid profile will studied total cholesterol TC triglycerides TG and cholesterol of high-density lipoproteins HDL Diakon-DS Russia content of cholesterol in low-density lipoproteins LDL and very low density lipoproteins VLDL will calculate as well as atherogenic factor AF Study of the inflammatory response will conduct by determining the concentration of basic biomarkers - high-sensitivity C-reactive protein hs-CRP DRG USA human tissue inhibitor of metalloproteinase-1 TIMP-1 eBioscience Austria according to the manufacturers protocols of test systems via immunoenzyme method The presence of microalbuminuria will determine using test strips Mikroalbufan Lachema Czech Republic the ratio albumin creatinine in urine will calculated
Statistical processing will perform using software Statistica 60 StatSoft USA with calculation of average M and standard error of the average m Methods of descriptive statistics will use comparison of performance in groups will perform by parametric Students t-test and non-parametric Pearson χ2 test Fishers exact test Mann-Whitney test statistics For all types of analysis the differences at p 005 will consider statistically significant
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