A Pilot Study of Allopurinol to Prevent Kidney Function Loss in Type 1 Diabetes (PERL)
Recent evidence from epidemiological studies suggests that serum uric acid levels higher than average predispose diabetic patients to kidney damage. The purpose of this study is to gather preliminary information on whether lowering serum uric acid by means of oral allopurinol (a drug commonly used for the treatment of gout) can be used to prevent or delay the loss of kidney function that may accompany diabetes. The results of this study will help us design a larger study to find out whether this medication can prevent kidney problems, in particular the loss of kidney function, in people with type 1 diabetes.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Pilot Study of Allopurinol to Prevent GFR Loss in Type 1 Diabetes.|
- Glomerular filtration rate at the end of the treatment period [ Time Frame: 2 years from the date of randomization ] [ Designated as safety issue: No ]Glomerular fitlration rate (GFR) at the end of the 2-year treatment measured by the plasma clearance of non-radioactive iohexol and adjusted for the GFR at baseline.
- Time to serum creatinine doubling or end stage renal disease [ Time Frame: From the date of randomization until the date of the first documented creatinine doubling or the first occurrence of end stage renal disease, whichever comes first, assessed up to 2 years ] [ Designated as safety issue: No ]Serum creatinine doubling is in reference to baseline creatinine values. End stage renal disease is defined as measured GFR <= 15 ml/min/1.73 m2 or start of hemodialysis or kidney transplant.
- Urinary albumin excretion rate in the last four months of the intervention period. [ Time Frame: From 84 to 104 weeks from the date of randomization ] [ Designated as safety issue: No ]Median urinary albumin excretion rate during the last four months of the treatment period (measured at 84, 96, 104 weeks) adjusted for the urinary albumin excretion rate at baseline
- Time to fatal or non-fatal cardiovascular events [ Time Frame: From the date of randomization until the date of first documented event, assessed up to 2 years ] [ Designated as safety issue: No ]Fatal or non-fatal cardiovascular events are defined as a composite of CVD death (ICD-10 code I10 to I74.9), myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous coronary intervention.
- Glomerular filtration rate trajectory during the treatment period [ Time Frame: From the date of randomization to the end of treatment (2 years from randomization) ] [ Designated as safety issue: No ]Glomerular fitration rate (GFR) trajectory (as defined by the slope and intercept) during the entire treatment period estimated from quarterly serum creatinine and cystatin C measurements using the CKD-EPI SCr and the CKD-EPI SCr-SCysC equations.
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Active Comparator: Allopurinol
Oral allopurinol will be titrated from 100 to 400 mg per day on the basis of serum uric acid levels with the goal of decreasing serum levels to 2.5-4.5 mg/dl, with a reduction of at least 30% from baseline levels. The dose will range from 100 to 400 mg per day if the GFR is ≥50 ml/min, and between 100 and 300 mg per day if the GFR is in the 15-50 ml/min range. Subjects will be given four tablets per day to be taken orally following meals, two in the morning and two in the evening. A dosage of 100 mg will be given as a 100 mg tablet plus three placebo tablets, 200 mg as two 100 mg and two placebo tablets, 300 mg as three 100 mg and one placebo tablet, 400 mg as four 100 mg tablets. Subjects randomized to placebo will be given four placebo tablets.
Placebo Comparator: Placebo
Subjects will be given four placebo (inactive) tablets per day to be taken orally following meals, two in the morning and two in the evening.
|Contact: Alessandro Doria, MD PhD MPH||(617) email@example.com|
|Contact: S. Michael Mauer, MD||(612) firstname.lastname@example.org|
|United States, Massachusetts|
|Joslin Diabetes Center||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Alessandro Doria, MD PhD MPH 617-309-2406 email@example.com|
|Contact: Chuanyun Gao, MD (617) 309-4648 firstname.lastname@example.org|
|Principal Investigator: Alessandro Doria, MD PhD MPH|
|Sub-Investigator: Chuanyun Gao, MD|
|Sub-Investigator: Robert Stanton, MD|
|Steno Diabetes Center||Recruiting|
|Gentofte, Denmark, DK-2820|
|Contact: Peter Rossing, MD +45 4443-7310 email@example.com|
|Principal Investigator: Peter Rossing, MD|
|Principal Investigator:||Alessandro Doria, MD PhD MPH||Joslin Diabetes Center|
|Study Chair:||S. Michael Mauer, MD||University of Minnesota - Clinical and Translational Science Institute|