Ignite Creation Date:
2024-05-06 @ 7:06 AM
Last Modification Date:
2024-10-26 @ 11:44 AM
Study NCT ID:
NCT02467478
Status:
COMPLETED
Last Update Posted:
2023-01-19
First Post:
2015-06-08
Brief Title:
Linagliptins Effect on CD34 Stem Cells
Sponsor:
George Washington University
Organization:
George Washington University
Study Overview
Official Title:
Role of Linagliptin in Improving Renal Failure by Improving CD34 Stem Cell Number Function and Gene Expression in Renal Function Impaired Type 2 Diabetes Patients
Status:
COMPLETED
Status Verified Date:
2022-12
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:
Type 2 diabetes is a national epidemic Diabetes has undesirable effects on blood vessels which may contribute to heart disease Endothelial Progenitor Cells EPCs are found in the blood Research has shown that improving the survival of these special blood cells may decrease the harmful effects of diabetes on blood vessels and reduce or reverse heart disease Linagliptin is an Food and Drug Administration FDA approved prescription medicine used along with insulin or with oral medications to lower blood sugar in people with Type 2 diabetes It is in a class of diabetes medication called Dipeptidyl peptidase-4 DPP-4 inhibitors DPP-4 inhibitors have been shown to increase EPCs in patients with Type 2 diabetes
Hypothesis Both type 2 diabetes and Chronic Kidney Disease CKD are associated with poor stem cell number and function Poor viability and function of EPCs in CKD and diabetes The investigators hypothesize that use of Linagliptin along with Insulin may help reduce cardiovascular risk by improving EPC survival and function above and beyond adequate glucose metabolism control
Hypothesis Both type 2 diabetes and Chronic Kidney Disease CKD are associated with poor stem cell number and function Poor viability and function of EPCs in CKD and diabetes The investigators hypothesize that use of Linagliptin along with Insulin may help reduce cardiovascular risk by improving EPC survival and function above and beyond adequate glucose metabolism control
Detailed Description:
Type 2 diabetes is a national epidemic with significant macro and microvascular complications Insulin resistance in pre-diabetes and overt diabetes are associated with endothelial dysfunction
A few studies indicate that stem cells particularly EPCs can act as a suitable bio-marker for monitoring cardiovascular morbidity In this proposal the investigators suggest that EPCs or CD34 positive cells defined as CD34vascular endothelial growth factor receptor 2 VEGFR2 cells can act as a suitable cellular biomarker for estimating and following endothelial dysfunction in early type 2 diabetes patients with CKD EPCs have been shown to be dysfunctional in both CKD patients and type 2 Diabetes Mellitus DM patients
Linagliptin TRADJENTA tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus No dose adjustment is recommended for patients with renal impairment
EPCs have been used as a regenerative tool in ischemic myocardium and diabetic wound healing Endothelial dysfunction with associated inflammation may be a consequence of excess intra-cellular super-oxide presence in a setting of diabetes which is a pro-oxidative stress condition ultimately leading to poor EPC function and senescence
Though lifestyle modification has been proposed as a main stay for prevention and treatment of early type 2 diabetes several new therapies for diabetes have been developed in recent years Incretins and incretin mimetics appear to hold promise Mechanism of positive effect of exercise and oral hypoglycemic agents can be very different
DPP-4 inhibitors have been shown to increase EPCs in patients with type 2 diabetes reportedly via stromal cell-derived factor 1 SDF-1 alpha up-regulation Interestingly up-regulation of SDF-1 alpha and vascular endothelial growth factor VEGF both chemotactic factors increase mobilization and recruitment of EPCs in the face of acute ischemic injury for repair and regeneration
Several studies have shown positive effect of incretins Glucagon like peptide GLP-1 and incretin receptor agonists GLP-1 receptor agonists on cardiovascular risk factors in type 2 diabetes patients and even in patients with chronic heart failure and left ventricular dysfunction who do not have diabetes
DPP-4 Inhibitors may have cardio-protective effects of their own as they increase bio-availability of endogenous GLP-1 They improve blood flow and nitric oxide production in endothelium These are unique properties not demonstrated by other oral diabetes medications The mechanism underlying these effects may be mediated by increased nitric oxide bioavailability but is not completely known However these beneficial effects appear to be independent of glycemia reduction
It is however unknown whether Linagliptin will have any positive effect on human EPC function where two prominent cardiovascular risk factors co-exist such as CKD and type 2 diabetes
Therefore the investigators plan to investigate if Linagliptin can alter function and gene expression of CD34 cells in a setting of CKD and type 2 diabetes The investigators choose to look at non geriatric adult population with early type 2 diabetes less than 10 years of duration at an early phase of renal impairment stages 1-3
A few studies indicate that stem cells particularly EPCs can act as a suitable bio-marker for monitoring cardiovascular morbidity In this proposal the investigators suggest that EPCs or CD34 positive cells defined as CD34vascular endothelial growth factor receptor 2 VEGFR2 cells can act as a suitable cellular biomarker for estimating and following endothelial dysfunction in early type 2 diabetes patients with CKD EPCs have been shown to be dysfunctional in both CKD patients and type 2 Diabetes Mellitus DM patients
Linagliptin TRADJENTA tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus No dose adjustment is recommended for patients with renal impairment
EPCs have been used as a regenerative tool in ischemic myocardium and diabetic wound healing Endothelial dysfunction with associated inflammation may be a consequence of excess intra-cellular super-oxide presence in a setting of diabetes which is a pro-oxidative stress condition ultimately leading to poor EPC function and senescence
Though lifestyle modification has been proposed as a main stay for prevention and treatment of early type 2 diabetes several new therapies for diabetes have been developed in recent years Incretins and incretin mimetics appear to hold promise Mechanism of positive effect of exercise and oral hypoglycemic agents can be very different
DPP-4 inhibitors have been shown to increase EPCs in patients with type 2 diabetes reportedly via stromal cell-derived factor 1 SDF-1 alpha up-regulation Interestingly up-regulation of SDF-1 alpha and vascular endothelial growth factor VEGF both chemotactic factors increase mobilization and recruitment of EPCs in the face of acute ischemic injury for repair and regeneration
Several studies have shown positive effect of incretins Glucagon like peptide GLP-1 and incretin receptor agonists GLP-1 receptor agonists on cardiovascular risk factors in type 2 diabetes patients and even in patients with chronic heart failure and left ventricular dysfunction who do not have diabetes
DPP-4 Inhibitors may have cardio-protective effects of their own as they increase bio-availability of endogenous GLP-1 They improve blood flow and nitric oxide production in endothelium These are unique properties not demonstrated by other oral diabetes medications The mechanism underlying these effects may be mediated by increased nitric oxide bioavailability but is not completely known However these beneficial effects appear to be independent of glycemia reduction
It is however unknown whether Linagliptin will have any positive effect on human EPC function where two prominent cardiovascular risk factors co-exist such as CKD and type 2 diabetes
Therefore the investigators plan to investigate if Linagliptin can alter function and gene expression of CD34 cells in a setting of CKD and type 2 diabetes The investigators choose to look at non geriatric adult population with early type 2 diabetes less than 10 years of duration at an early phase of renal impairment stages 1-3
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None