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

Prior treatment

• Renal transplant or dialysis;
• Current therapy with fibrates or other PPAR-α agonists;
• Alcohol or drug abuse in the past 6 months;

Other illness

• Non-diabetic kidney disease;
• Allergy to fibrates or iodine containing substances;
• History of photosensitive skin rash or myositis;
• 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 two years of screening;
• History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV) infection;
• Serious medical problems other than diabetes, e.g. congestive heart failure, pulmonary insufficiency;

Lab values

• Persistent elevated unexplained blood creatinine phosphokinase level \>3 times the upper limit of normal;
• Current or past history of decompensated cirrhosis (defined as variceal bleeding, ascites, or hepatic encephalopathy and/or diagnosis of cirrhosis based on liver biopsy, imaging, or elastography and/or aspartate or alanine aminotransferase (AST or ALT) \>2 times the upper limit of normal at screening and/or total bilirubin \>1.3 times 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);
• Hemoglobin concentration \<11 g/dL (males), \<10 g/dL (females) or platelet count \<100,000/mm3 at screening;

Other

• Specific contraindications or indications for fibrates;
• 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 study requirements;
• Participation in another interventional study.
• Being incarcerated.

• 18 and 70 years of age, inclusive.
• Type 1 diabetes (T1D) continuously treated with insulin within one year from diagnosis. If the onset was after age 35, the presence of one or more of the following will also be required: a. documentation of the presence of circulating T1D-associated autoantibodies at diagnosis or at any other time; b. history of hospitalization for DKA; c. plasma C-peptide below the limit of detection with standard 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 the trial and micro- or macro-albuminuria (urinary albumin excretion rate \[AER\]=30-5000 mg/24 hr or albumin creatinine ratio \[ACR\]=30-5000 mg/g if not on renin-angiotensin system blocker (RASB) agents, or AER=18-5000 mg/24 hr or ACR 18-5000 mg/g range, if on RASB agents) on at least two occasions during the PERL allopurinol trial. All others 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 at screening. The upper and the lower limits should be decreased by 1 ml/min/1.73 m2 for each year over age 60 (with a lower limit of 35 ml/min/1.73m2) and by 10 ml/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.