The Effect of Uric Acid Lowering in Type 1 Diabetes

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.

Conditions

• Type 1 Diabetes Mellitus

Interventions

DRUG

Febuxostat

Oral tablet, 80mg, OD, 8 weeks

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Toronto General Hospital

  collaborator OTHER

• University of Toronto

  collaborator OTHER

• University Health Network, Toronto

  lead OTHER

Principal Investigators

• David ZI Cherney, MD, PhD · University Health Network, Toronto

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-12-18

Primary Completion

2015-09-22

Completion

2015-09-22

Countries

• Canada

Study Locations