Ignite Creation Date:
2024-05-06 @ 3:15 AM
Last Modification Date:
2024-10-26 @ 11:30 AM
Study NCT ID:
NCT02245633
Status:
UNKNOWN
Last Update Posted:
2014-09-19
First Post:
2014-09-09
Brief Title:
Correlation Between Vitamin D Levels to ADAMTS13 VWF and Micro RNA Expression in Diabetic Hemodialysis Patients
Sponsor:
Meir Medical Center
Organization:
Meir Medical Center
Study Overview
Official Title:
None
Status:
UNKNOWN
Status Verified Date:
2014-09
Last Known Status:
RECRUITING
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 research is to study how vitamin D affects various aspects of the disease process such as inflammation coagulation ADAMTS13 and WVF and miRNAs in Diabetic kidney disease hemodialysis patients
Diabetes mellitus DM is one of the most common chronic diseases in nearly all countries Diabetic kidney disease DKD traditionally has been referred to as diabetic nephropathy and is one of the microvascular complications of diabetes Diabetic kidney disease DKD occurs in 25-40 of patients with diabetes
Some studies have shown that the high risk of cardiovascular disease in diabetic patients with nephropathy is associated with increased plasma levels of von Willebrand factor VWF and decreased ADAMTS13 levels VWF is a glycoprotein that plays an important role in platelet thrombus formation whereas ADAMTS13 is a proteolytic enzyme that is responsible for degradation of large multimers of VWF released in the plasma by endothelial cells and platelets Patients with both chronic kidney disease and diabetes have been shown to have higher plasma levels of VWF and decreased ADAMTS13 activity compared to healthy controls
Increased plasma levels of VWF which reflects damage to endothelial cells and a hypercoagulability state have been reported in atherosclerosis and diabetes Thus VWF and ADAMTS13 seem to be important players in the interface between diabetic nephropathy hypercoagulability and atherosclerotic cardiovascular disease Vitamin D deficiency is a risk factor for DM and hypertension The investigators previous studies showed that adding calcitriol activated vitamin D to endothelial and vascular smooth muscle cells significantly down-regulated the inflammatory response of gene and protein expression involved in the nuclear factor kappa-light-chain-enhancer of activated B cells NFĸB signal transduction pathway Micro RNA miRNA are short noncoding RNAs 22-25 nucleotides long As an endogenous production transcript miRNAs can bind to the 3 untranslated regions 3 UTR of its target messenger RNA mRNA in an imperfect complementary manner leading to post-transcriptional gene silencing As a result miRNAs can inhibit gene expression via mRNA degradation translation inhibition or transcriptional inhibitionThe critical role of miRNAs has been established in several cellular and biologic processes such as proliferation differentiation and development and in the regulation of genes related to immune responses cancer and insulin secretion MiRNA are involved in various biological processes and become novel biomarkers modulators and therapeutic targets for diseases such as cancer atherosclerosis and DM
Significance The high prevalence of cardiovascular morbidity and mortality in patients with DM on chronic hemodialysis remains a significant clinical problem and the finding of potential new biomarkers should be further investigated This study aims to establish a link between ADAMTS13 VWF miRNA expression and vitamin D levels that can contribute to the development of new treatments for hemodialysis patients with diabetes
Methods Each hemodialysis patient with diabetes in the investigators institute will be asked to participate in the study After explaining the research goals patients that agree to participate will sign an informed consent The investigators estimate that the study will include 70 patients Each patient will be assessed by a physician and 4 vials of blood will be taken while the patient is connected to the dialysis machine The blood will be sent to the laboratory to check 1 chemistry 2 1-25 vitamin D and 25- vitamin D levels 3 ADAMTS13 activity and VWF and 4 miRNA extraction The patients will be grouped according to vitamin D levels deficient sufficient and ADAMTS13 VWF and miRNA expression will be compared between the groups
Diabetes mellitus DM is one of the most common chronic diseases in nearly all countries Diabetic kidney disease DKD traditionally has been referred to as diabetic nephropathy and is one of the microvascular complications of diabetes Diabetic kidney disease DKD occurs in 25-40 of patients with diabetes
Some studies have shown that the high risk of cardiovascular disease in diabetic patients with nephropathy is associated with increased plasma levels of von Willebrand factor VWF and decreased ADAMTS13 levels VWF is a glycoprotein that plays an important role in platelet thrombus formation whereas ADAMTS13 is a proteolytic enzyme that is responsible for degradation of large multimers of VWF released in the plasma by endothelial cells and platelets Patients with both chronic kidney disease and diabetes have been shown to have higher plasma levels of VWF and decreased ADAMTS13 activity compared to healthy controls
Increased plasma levels of VWF which reflects damage to endothelial cells and a hypercoagulability state have been reported in atherosclerosis and diabetes Thus VWF and ADAMTS13 seem to be important players in the interface between diabetic nephropathy hypercoagulability and atherosclerotic cardiovascular disease Vitamin D deficiency is a risk factor for DM and hypertension The investigators previous studies showed that adding calcitriol activated vitamin D to endothelial and vascular smooth muscle cells significantly down-regulated the inflammatory response of gene and protein expression involved in the nuclear factor kappa-light-chain-enhancer of activated B cells NFĸB signal transduction pathway Micro RNA miRNA are short noncoding RNAs 22-25 nucleotides long As an endogenous production transcript miRNAs can bind to the 3 untranslated regions 3 UTR of its target messenger RNA mRNA in an imperfect complementary manner leading to post-transcriptional gene silencing As a result miRNAs can inhibit gene expression via mRNA degradation translation inhibition or transcriptional inhibitionThe critical role of miRNAs has been established in several cellular and biologic processes such as proliferation differentiation and development and in the regulation of genes related to immune responses cancer and insulin secretion MiRNA are involved in various biological processes and become novel biomarkers modulators and therapeutic targets for diseases such as cancer atherosclerosis and DM
Significance The high prevalence of cardiovascular morbidity and mortality in patients with DM on chronic hemodialysis remains a significant clinical problem and the finding of potential new biomarkers should be further investigated This study aims to establish a link between ADAMTS13 VWF miRNA expression and vitamin D levels that can contribute to the development of new treatments for hemodialysis patients with diabetes
Methods Each hemodialysis patient with diabetes in the investigators institute will be asked to participate in the study After explaining the research goals patients that agree to participate will sign an informed consent The investigators estimate that the study will include 70 patients Each patient will be assessed by a physician and 4 vials of blood will be taken while the patient is connected to the dialysis machine The blood will be sent to the laboratory to check 1 chemistry 2 1-25 vitamin D and 25- vitamin D levels 3 ADAMTS13 activity and VWF and 4 miRNA extraction The patients will be grouped according to vitamin D levels deficient sufficient and ADAMTS13 VWF and miRNA expression will be compared between the groups
Detailed Description:
None
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