The Effect of Uric Acid Lowering in Type 1 Diabetes
Status:
Completed
Trial end date:
2015-09-22
Target enrollment:
Participant gender:
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.
Phase:
Phase 4
Details
Lead Sponsor:
University Health Network, Toronto
Collaborators:
Canadian Institutes of Health Research (CIHR) Toronto General Hospital University of Toronto