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

• Status: Not yet recruiting
• Trial end date: 2024-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Diabetic kidney disease remains the leading cause of end-stage kidney disease (ESKD), rising in frequency in parallel with the epidemic of diabetes worldwide. The estimated lifetime risk of kidney disease in persons with type 1 diabetes (T1D) has been reported to be as high as 50-70%, although risk may be lower in excellent care environments. Two previous studies have suggested that a generic drug used to lower fats in blood (fenofibrate) may protect the kidney from damage due to diabetes. These data, however, were obtained among people with type 2 diabetes with clinical characteristics optimized for cardiovascular studies. Thus, a clinical trial specifically designed to evaluate the effects on the kidney is required to firmly show that this drug can prevent kidney damage in T1D. The goals of the present pilot study are to demonstrate the feasibility of such trial, gather essential information for designing and planning this study, and generate preliminary data. To this end, 40 participants with T1D and early-to-moderate diabetic kidney disease (DKD), at high risk of ESKD, will be enrolled at two clinical sites and assigned in a 1:1 ratio to treatment with fenofibrate or placebo for 18 months. Kidney function will be measured at the beginning and at the end of the study to evaluate the effect of fenofibrate.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Alessandro Doria
• Collaborators: University of Michigan; University of Minnesota
• Treatments: Fenofibrate

Criteria

Inclusion Criteria:

• 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=300-5000 mg/24 hrs or ACR=300-5000 mg/g) on two occasions during the two 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.

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 the upper limit of normal;

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

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

• History of clinically significant hepatic disease including hepatitis B or C and/or persistently elevated serum liver enzymes at screening and/or history of HBV/HCV positivity;

• 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 study requirements;

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

• Participation in another interventional study.

• Being incarcerated.