Ignite Creation Date:
2024-05-05 @ 9:36 PM
Last Modification Date:
2024-10-26 @ 10:06 AM
Study NCT ID:
NCT00921570
Status:
COMPLETED
Last Update Posted:
2009-06-17
First Post:
2009-06-15
Brief Title:
The Effects of Renin Angiotensin System Blockage RAS Calcium Channel Blocker and Combined Drugs on TWEAK PTX3 and FMD Levels in Diabetic Proteinuric Patients With Hypertension
Sponsor:
Gulhane School of Medicine
Organization:
Gulhane School of Medicine
Study Overview
Official Title:
The Effects of Renin Angiotensin System Blockage RAS Calcium Channel Blocker and Combine Drugs on TWEAK PTX3 and FMD Levels in Diabetic Proteinuric Patients With Hypertension
Status:
COMPLETED
Status Verified Date:
2009-06
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:
Diabetic nephropathy DN is the most important complication of diabetes mellitus DM and the most common cause of end-stage renal disease ESRD Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria 300 mgd or 200 mcgmin that is confirmed on at least 2 occasions 3 to 6 months apart a relentless decline in the glomerular filtration rate GFR and elevated arterial blood pressure In addition to the renal hemodynamic alterations patients with overt diabetic nephropathy dipstick-positive proteinuria and decreasing GFR generally develop systemic hypertension Hypertension is an adverse factor in all progressive renal diseases and seems especially so in diabetic nephropathy The deleterious effects of hypertension are likely directed at the vasculature and microvasculature Use of angiotensin converting enzyme ACE inhibitors andor angiotensin receptor blockers ARBs strict glycemic control and use of antilipidemic drugs may improve progression of DN
TNF-like weak inducer of apoptosis TWEAK TNFSF12 is a member of the TNF superfamily of structurally related cytokines The human TWEAK gene encodes a 249-amino acid type II transmembrane glycoprotein 30 kD TWEAK may be expressed as a full-length membrane-bound protein and as a 156-amino acid 18-kD soluble protein sTWEAK that results from proteolysis of TWEAK TWEAK gene is expressed in many tissues including brain kidney heart arterial wall monocytes and macrophages Reduced soluble TNF-like weak inducer of apoptosis sTWEAK plasma levels have been reported both in patients with subclinical atherosclerosis and chronic kidney disease CKD
Long pentraxin 3 PTX3 is a multimeric inflammatory mediator Increased serum PTX3 levels have been reported among end-stage renal disease patients Moreover PTX3 has been suggested to represent a novel mortality risk factor and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease CKD
There is no data about the effects of Renin angiotensin system blockage RAS calcium channel blocker and combined drugs on TWEAK and PTX3 levels in diabetic proteinuric patients with hypertension The aim of this study was to find out whether the beneficial effects of RAS blockage calcium channel blocker and combined drugs in diabetic hypertensive proteinuric patients has any relation with the alteration of TWEAK and PTX3 levels The investigators searched for the effects of angiotensin II AII receptor blocker Valsartan 160 mg calcium channel blocker Amlodipine 10 mg and AII receptor blocker plus calcium channel blocker Valsartan 160 mg Amlodipine 10 mg on the clinical and laboratory parameters of diabetic hypertensive proteinuric patients
TNF-like weak inducer of apoptosis TWEAK TNFSF12 is a member of the TNF superfamily of structurally related cytokines The human TWEAK gene encodes a 249-amino acid type II transmembrane glycoprotein 30 kD TWEAK may be expressed as a full-length membrane-bound protein and as a 156-amino acid 18-kD soluble protein sTWEAK that results from proteolysis of TWEAK TWEAK gene is expressed in many tissues including brain kidney heart arterial wall monocytes and macrophages Reduced soluble TNF-like weak inducer of apoptosis sTWEAK plasma levels have been reported both in patients with subclinical atherosclerosis and chronic kidney disease CKD
Long pentraxin 3 PTX3 is a multimeric inflammatory mediator Increased serum PTX3 levels have been reported among end-stage renal disease patients Moreover PTX3 has been suggested to represent a novel mortality risk factor and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease CKD
There is no data about the effects of Renin angiotensin system blockage RAS calcium channel blocker and combined drugs on TWEAK and PTX3 levels in diabetic proteinuric patients with hypertension The aim of this study was to find out whether the beneficial effects of RAS blockage calcium channel blocker and combined drugs in diabetic hypertensive proteinuric patients has any relation with the alteration of TWEAK and PTX3 levels The investigators searched for the effects of angiotensin II AII receptor blocker Valsartan 160 mg calcium channel blocker Amlodipine 10 mg and AII receptor blocker plus calcium channel blocker Valsartan 160 mg Amlodipine 10 mg on the clinical and laboratory parameters of diabetic hypertensive proteinuric patients
Detailed Description:
The patients who were non-obese BMI30kgm2 non dyslipidemic total cholesterol 200mgdl Triglyceride150mgdl and free of cardiovascular events negative medical history negative ECG findings were investigated for enrollment CKD stage 1 patients older than 18 years of age and willing to participate to the study were screened From the 375 patients with established type 2 diabetes mellitushypertension 174 had proteinuria andor hypertension 24 h protein excretion 1-2 gday systolic blood pressures 140mmHg andor diastolic blood pressures 90 mmHg respectively All cases were first referrals and at the time of the study all were off treatment Patients with history of coronary artery disease smokers and those taking statins or renin-angiotensin blockers were excluded because of the effect of these factors on endothelial dysfunction Of 174 screened patients 107 met the study criteria and were included in this study The duration of proteinuria and diabetic nephropathy after initial diagnosis was not known
The exclusion criteria were as follows ANephrotic syndrome Bcoronary heart disease patients with ischemic ST-T alterations and voltage criteria for LVH on electrocardiogram and with history of revascularization or myocardial infarction C elevated liver enzymes AST or ALT levels 40UL and D renal failure serum creatinine levels 13 mgdl In order to evaluate the effect of RAS blockade on plasma TWEAK and PTX3 concentrations patients with proteinuria were given an AII receptor blocker Valsartan 160 mg calcium channel blocker Amlodipine 10 mg and combine drug Valsartan 160 mg Amlodipine 10 mg for 12 weeks The effect of RAS blockade on insulin sensitivity and proteinuria was also investigated
After the intervention period blood samples were obtained for assay of plasma TWEAK and PTX3 concentrations HbA1c and insulin resistance scores HOMA-IR
Urine samples were also collected over a 24-hour period to determine the degree of proteinuria
The exclusion criteria were as follows ANephrotic syndrome Bcoronary heart disease patients with ischemic ST-T alterations and voltage criteria for LVH on electrocardiogram and with history of revascularization or myocardial infarction C elevated liver enzymes AST or ALT levels 40UL and D renal failure serum creatinine levels 13 mgdl In order to evaluate the effect of RAS blockade on plasma TWEAK and PTX3 concentrations patients with proteinuria were given an AII receptor blocker Valsartan 160 mg calcium channel blocker Amlodipine 10 mg and combine drug Valsartan 160 mg Amlodipine 10 mg for 12 weeks The effect of RAS blockade on insulin sensitivity and proteinuria was also investigated
After the intervention period blood samples were obtained for assay of plasma TWEAK and PTX3 concentrations HbA1c and insulin resistance scores HOMA-IR
Urine samples were also collected over a 24-hour period to determine the degree of proteinuria
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