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

Inclusion Criteria:

• 18 and 70 years of age, inclusive.

• Type 1 diabetes (T1D) continuously treated with insulin within one year fromdiagnosis. If the onset was after age 35, the presence of one or more of thefollowing will also be required: a. documentation of the presence of circulatingT1D-associated autoantibodies at diagnosis or at any other time; b. history ofhospitalization for DKA; c. plasma C-peptide below the limit of detection withstandard assay (with concurrent blood glucose >100 mg/dl)

• Duration of T1D ≥ 8 years.

• Diabetic kidney disease at high risk of progression to ESKD, defined as follows:PERL allopurinol study participants: iGFR decline ≥3 ml/min/1.73 m2/year during thetrial and micro- or macro-albuminuria (urinary albumin excretion rate [AER]=30-5000mg/24 hr or albumin creatinine ratio [ACR]=30-5000 mg/g if not on renin-angiotensinsystem blocker (RASB) agents, or AER=18-5000 mg/24 hr or ACR 18-5000 mg/g range, ifon RASB agents) on at least two occasions during the PERL allopurinol trial. Allothers participants: macroalbuminuria (AER=100-5000 mg/24 hrs or ACR=100-5000 mg/g)on two occasions during the three years before screening and/or at screening;

• Estimated GFR (eGFR) based on serum creatinine between 40 and 99.9 ml/min/1.73 m2 atscreening. The upper and the lower limits should be decreased by 1 ml/min/1.73 m2for each year over age 60 (with a lower limit of 35 ml/min/1.73m2) and by 10ml/min/1.73 m2 for strict vegans.

• Valid baseline (Visit 2) iGFR measurement.

• Current treatment with RASB, unless contraindicated;

• Willing and able to comply with schedule of events and protocol requirements,including written informed consent.

Exclusion Criteria:

• Renal transplant or dialysis;

• Non-diabetic kidney disease;

• Allergy to fibrates or iodine containing substances;

• Current therapy with fibrates or other PPAR-α agonists;

• Specific contraindications or indications for fibrates;

• History of photosensitive skin rash or myositis;

• Persistent elevated unexplained blood creatinine phosphokinase level >3 times theupper limit of normal;

• History of pancreatitis, deep vein thrombosis (DVT) or pulmonary embolism;

• History of cholelithiasis unless gallbladder has been removed;

• Cancer treatment (excluding non-melanoma skin cancer treated by excision) within twoyears of screening;

• Current or past history of decompensated cirrhosis (defined as variceal bleeding,ascites, or hepatic encephalopathy and/or diagnosis of cirrhosis based on liverbiopsy, imaging, or elastography and/or aspartate or alanine aminotransferase (ASTor ALT) >2 times the upper limit of normal at screening and/or total bilirubin >1.3times the upper limit of normal at screening (in the case of Gilbert syndrome,direct bilirubin >1.5 times the upper limit of normal at screening);

• History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)infection;

• Hemoglobin concentration <11 g/dL (males), <10 g/dL (females) or platelet count <100,000/mm3 at screening;

• Alcohol or drug abuse in the past 6 months;

• Blood donation within 3 months of screening;

• Breastfeeding, pregnancy, or unwillingness to be on contraception during the trial;

• Poor mental function or any reasons to expect difficulty in complying with studyrequirements;

• Serious medical problems other than diabetes, e.g. congestive heart failure,pulmonary insufficiency;

• Participation in another interventional study.

• Being incarcerated.