A Pilot Study of Allopurinol to Prevent Kidney Function Loss in Type 1 Diabetes

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 < 26 kg/m2 at the time of diagnosis;

- Duration of T1D ≥ 5 years;

- Presence of microalbuminuria or moderate macroalbuminuria (at least two out of three
consecutive urinary albumin excretion rates [AER] or urinary albumin/creatinine ratios
(ACR) measured during the preceding two years in the 30-1500 mg/24 hr or the 30-1500
mg/g range, respectively).

- Estimated GFR (based on serum creatinine and the CKD-EPI equation) between 35 and 109
ml/min/1.73 m2 at the screening visit.

- Measured GFR between 45 and 99 ml/min/1.73 m2 at the end of the run-in period;

- Serum UA ≥ 4.5 mg/dl at the screening visit.

- Willing to comply with schedule of events and protocol requirements.

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.