Ignite Creation Date:
2024-05-06 @ 3:39 AM
Last Modification Date:
2024-10-26 @ 11:37 AM
Study NCT ID:
NCT02344602
Status:
COMPLETED
Last Update Posted:
2018-01-16
First Post:
2015-01-09
Brief Title:
The Effect of Uric Acid Lowering in Type 1 Diabetes
Sponsor:
University Health Network Toronto
Organization:
University Health Network Toronto
Study Overview
Official Title:
A Deep Phenotyping Approach to Assess the Effect of Uric Acid Lowering in Patients With Uncomplicated Type 1 Diabetes Mellitus
Status:
COMPLETED
Status Verified Date:
2018-01
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:
None
Brief Summary:
Patients with type 1 diabetes mellitus T1DM are at high risk of developing kidney complications potentially leading to end stage renal disease Uric acid UA the end product of purine metabolism emerged as an important determinant of renal and vascular injury due to its ability activate the renin-angiotensin-aldosterone system RAAS and increase production of harmful reactive oxygen species ROS ROS cause progressive endothelial cell dysfunction inflammation tissue fibrosis and eventually cell death These processes are enhanced in DM because of the effect of hyperglycemia
Since existing preventive drug therapies fail to completely prevent kidney damage an examination of the effect of UA lowering against initiation and progression of renal and vascular complications is therefore of the utmost importance The purpose of this study is to examine the effect of UA lowering with febuxostat on renal and systemic vascular function in patients with uncomplicated T1DM It was hypothesized that UA lowering will improve kidney and systemic vascular function through effects on blood vessel function and anti-inflammatory effect
Kidney and blood vessel function will be assessed under conditions of normal and high blood sugar levels before and after 8 weeks of treatment with the UA lowering drug febuxostat in patients with diabetes and during normoglycemia only in health controls
Current treatment for renal and vascular complications in DM patients includes blockade of the RAAS Unfortunately angiotensin converting enzyme inhibitors ACEi and angiotensin II AngII receptor blockers ARBs lead to incomplete RAAS suppression and do not completely prevent renal or vascular complications Moreover dual RAAS blockade increases renal and cardiovascular risk Recent experimental work suggests that UA lowering therapies can block the RAAS suppress inflammation and promote renal and systemic vascular protection Therefore our study is critical in determining the possible role of early UA lowering on renal and systemic hemodynamic dysfunction in young patients with T1DM
Since existing preventive drug therapies fail to completely prevent kidney damage an examination of the effect of UA lowering against initiation and progression of renal and vascular complications is therefore of the utmost importance The purpose of this study is to examine the effect of UA lowering with febuxostat on renal and systemic vascular function in patients with uncomplicated T1DM It was hypothesized that UA lowering will improve kidney and systemic vascular function through effects on blood vessel function and anti-inflammatory effect
Kidney and blood vessel function will be assessed under conditions of normal and high blood sugar levels before and after 8 weeks of treatment with the UA lowering drug febuxostat in patients with diabetes and during normoglycemia only in health controls
Current treatment for renal and vascular complications in DM patients includes blockade of the RAAS Unfortunately angiotensin converting enzyme inhibitors ACEi and angiotensin II AngII receptor blockers ARBs lead to incomplete RAAS suppression and do not completely prevent renal or vascular complications Moreover dual RAAS blockade increases renal and cardiovascular risk Recent experimental work suggests that UA lowering therapies can block the RAAS suppress inflammation and promote renal and systemic vascular protection Therefore our study is critical in determining the possible role of early UA lowering on renal and systemic hemodynamic dysfunction in young patients with T1DM
Detailed Description:
Uric acid UA was recently suggested to exert deleterious effects on blood pressure and renal function even when baseline UA levels are within the normal range UA activates the renin angiotensin-aldosterone system RAAS increases oxidative stress and promotes inflammation As a consequence higher UA levels are associated with metabolic abnormalities insulin resistance hyperglycemia cardiovascular disease hypertension endothelial dysfunction arterial stiffness cardiac diastolic dysfunction and kidney function abnormalities hyperfiltration - a marker for intraglomerular hypertension proteinuria Thus pharmacologic UA lowering may promote renal and cardiovascular protection The mechanisms underlying these protective effects in humans prior to the onset of clinical disease remain unknown
This study is focused on the prevention of complications in young normotensive type 1 diabetes mellitus T1DM patients with normal renal function and UA levels The study will examine the effect of UA lowering with febuxostat FBX on renal hemodynamic function vascular function and urinary inflammatory biomarkers Based on substantial supportive pre-clinical and epidemiological data we hypothesize that lowering UA levels that are within normal range at baseline will 1 ameliorate hemodynamic abnormalities characteristic of T1DM and reduce renal and systemic hypertensive responses to hyperglycemia 2 ameliorate endothelial function abnormalities characteristic of T1DM 3 reduce urinary inflammatory cytokineschemokine excretion
This study is focused on the prevention of complications in young normotensive type 1 diabetes mellitus T1DM patients with normal renal function and UA levels The study will examine the effect of UA lowering with febuxostat FBX on renal hemodynamic function vascular function and urinary inflammatory biomarkers Based on substantial supportive pre-clinical and epidemiological data we hypothesize that lowering UA levels that are within normal range at baseline will 1 ameliorate hemodynamic abnormalities characteristic of T1DM and reduce renal and systemic hypertensive responses to hyperglycemia 2 ameliorate endothelial function abnormalities characteristic of T1DM 3 reduce urinary inflammatory cytokineschemokine excretion
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