CompletedPhase 4

The Effect of Uric Acid Lowering in Type 1 Diabetes

Canada73 participantsStarted 2012-12-18

Plain-language 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.

Who can participate

Age range

18 Years – 40 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Age 18-40 years old * Normoalbuminuria 24 hour urine collection * Body mass index 18-30 kg/m2 at screening * Subject able, willing to perform assessments * Normal electrocardiogram * Normal renal (estimated GFR\>60 ml/min) * Clinic blood pressure \<140/90 mmHg * Type 1 DM, duration of diabetes \>1 years * Able to take medications every day * Signed and dated written informed consent on the screening visit in accordance with GCP and local legislation * Hemoglobin A1c 6-11% * Normal uric acid levels Exclusion Criteria: * Cardiac, lung or peripheral vascular disease or stroke, gout * Hypertension, or on BP-lowering medicine * History of proliferative retinopathy * Diagnosis of brittle diabetes based on investigator judgement * Allergy to either allopurinol or probenecid * Pregnancy, breastfeeding, no reliable contraception * Oral contraceptives (due to effects on the RAS) * Alcohol or tobacco within 24 hours prior to the study * Uric acid ≥420 μmol/L or taking uric acid lowering agents * Use of agents that influence GFR or interfere with purine metabolism (didanosine, azothioprine, methotrexate, NSAIDs, mycophenolate) * Pancreas, pancreatic islet cells or renal transplant recipient * Medical history of cancer or treatment for cancer in the last five years prior to screening * T1DM treatment with any other drugs to reduce blood glucose except insulin within 6 months prior to screening (example: off-label use of metformin) * Known autonomic neuropathy and …

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

The Change in Glomerular Filtration Rate (GFR) After an 8 week Treatment with Febuxostat

Timeframe: Before and after an 8 week treatment with febuxostat.

The Change in Effective Renal Plasma Flow (ERPF) After an 8 week Treatment with Febuxostat

Timeframe: Before and after an 8 week treatment with febuxostat

Trial details

NCT IDNCT02344602

SponsorUniversity Health Network, Toronto

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2015-09-22

View on ClinicalTrials.gov More Type 1 Diabetes Mellitus trials