Type 1 diabetes, microalbuminuria or macroalbuminuria and mildly impaired kidney function.
Conditions
Interventions
Trade Name: Allopurinol (Hexanurat)
Product Name: Hexanurat
Pharmaceutical Form:
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use
Sponsors
Joslin Diabetes Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • • Male or female T1D patients between 18 and 60 years of age. • T1D diagnosed before age 35 and continuously treated with insulin within one year from diagnosis. If the onset was between ages 31 and 35, body mass index (BMI) will be required to be =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • • History of gout requiring uric acid lowering therapy or xanthinuria or other indications for uric acid lowering therapy such as cancer chemotherapy or extremely high serum uric acid values (=12 mg/dl) • Recurrent renal calculi. • Use of urate-lowering agents within 3 months before enrollment. • Current use of azathioprine, 6-mercaptopurine, didanosine, warfarin, tamoxifen, amoxicillin/ampicillin, or other drugs interacting with allopurinol. • Known allergy to xanthine-oxidase inhibitors or iodine containing substances. • HLA B*58:01 genotype (determined at the time of randomization) indicating increased risk of Stevens-Johnson syndrome in response to allopurinol. • Renal transplant. • Non-diabetic kidney disease as indicated by medical history and/or laboratory findings. • SBP>160 or DBP >100 mmHg at screening or SBP>140 or DBP>90 mmHg at the end of the run-in period. • Cancer treatment within two years before enrollment. • History of clinically significant hepatic disease including hepatitis B or C and/or ALT (SGPT) >2.50 x ULN at screening; • History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV); • Hemoglobin concentration <11 g/dL (males), <10 g/dL (females) at screening. • Platelet count <100,000/mm3 at screening. • History of alcohol or drug abuse in the past 12 months • Breastfeeding or pregnancy or unwillingness to be on contraception. • Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study. • Serious pre-existing medical problems other than diabetes, e.g. congestive heart failure, pulmonary insufficiency.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To obtain estimates of the distribution of the primary outcome (GFR decline) in the study population in order to properly power a future pivotal clinical trial. ;Secondary Objective: 2. To pilot study procedures, such as the run-in period, the allopurinol dosage adjustment algorithms, and the iohexol clearance GFR measurement. 3. To gather preliminary data about the efficacy of allopurinol in reducing GFR decline over 2 years.;Primary end point(s): GFR at the end of the 2-year intervention measured by the plasma clearance of non-radioactive iohexol (iGFR) and adjusted for the GFR at baseline;Timepoint(s) of evaluation of this end point: After 2 years study duration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Estimated GFR (eGFR) time trajectory estimated from quarterly serum creatinine and cystatin C measurements using the CKD-EPI SCr and the CKD-EPI SCr-SCysC equations. 2. Time to doubling of baseline serum creatinine value or ESRD (eGFR = 15 ml/min/1.73 m2). 3. Median urinary AER during the last three months of the intervention period, adjusted for the median urinary AER at baseline. Urinary AER will be determined in timed overnight urine collections brought by study participants to regular clinic visits, and expressed in ?g/minute and as urinary albumin creatinine ratios. 4. Time to fatal or non-fatal cardiovascular events, defined as the composite of CVD death (ICD-10 code I10 to I74.9), myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous coronary intervention. ;Timepoint(s) of evaluation of this end point: Throughout the duration of the study | — |
Countries
Denmark, United States
Contacts
Public ContactSection on Genetics and Epidemiolog
Joslin Diabetes Center
Outcome results
None listed