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

NCT04929379 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00000156
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Diabetic Nephropathies

Keywords

type 1 diabetes; diabetic kidney disease; fibrates

Outcome Measures

Primary Outcomes (3)

• Baseline-adjusted iGFR at 8 weeks after randomization

  GFR measured by iohexol plasma disappearance (ml/min/1.73 m2), adjusted by its baseline value

  8 weeks after randomization

• Baseline-adjusted iGFR at the end of the drug wash-out period

  GFR measured by iohexol plasma disappearance (ml/min/1.73 m2), adjusted by its baseline value

  84 weeks after randomization

• Baseline-adjusted levels of serum biomarkers of increased ESKD risk at the end of the drug wash-out period

  Levels of the following 21 serum biomarkers, adjusted by their baseline values: CD160, CD27, DLL1, EDA2R, EFNA4, EPHA2, GFRA1, IL1RT1, KIM1, LAYN, LTBR, PI3, PVRL4, RELT, SYND1, TNFR1, TNFR2, TNFRSF10A, TNFRSF4, TNFRSF6B, WFDC2

  84 weeks after randomization

Secondary Outcomes (25)

• Baseline-adjusted iGFR at the end of treatment

  76 weeks after randomization

• iGFR at the end of treatment

  76 weeks after randomization

• Baseline-adjusted eGFR-SCr at 8 weeks after randomization

  8 weeks after randomization

• Baseline-adjusted eGFR-SCr at the end of treatment

  76 weeks after randomization

• eGFR-SCr at the end of treatment

  76 weeks after randomization

Study Arms (2)

Fenofibrate

EXPERIMENTAL

145 mg oral fenofibrate daily for 76 weeks. Dosage is decreased to 48 mg daily if iGFR is or is estimated to be below 30 ml/min/1.73 m2.

Drug: Fenofibrate

Placebo

PLACEBO COMPARATOR

Inactive tablets identical to fenofibrate

Other: Placebo

Interventions

Fenofibrate DRUG

145 mg oral fenofibrate daily for 76 weeks. Dosage is decreased to 48 mg daily if iGFR is or is estimated to be below 30 ml/min/1.73 m2.

Fenofibrate

Placebo OTHER

Inactive tablets identical to fenofibrate

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• History of cholelithiasis unless gallbladder has been removed;
• Cancer treatment (excluding non-melanoma skin cancer treated by excision) within two years of screening;
• 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);
• 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;

Sponsors & Collaborators

• Alessandro Doria: lead
• University of Michigan: collaborator
• University of Minnesota: collaborator

Study Sites (4)

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Lahey Hospital and Medical center

Burlington, Massachusetts, 01805, United States

Location

Brehm Center for Diabetes Research / University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Related Publications (2)

• Davis TM, Ting R, Best JD, Donoghoe MW, Drury PL, Sullivan DR, Jenkins AJ, O'Connell RL, Whiting MJ, Glasziou PP, Simes RJ, Kesaniemi YA, Gebski VJ, Scott RS, Keech AC; Fenofibrate Intervention and Event Lowering in Diabetes Study investigators. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia. 2011 Feb;54(2):280-90. doi: 10.1007/s00125-010-1951-1. Epub 2010 Nov 4.

  PMID: 21052978 BACKGROUND

• Frazier R, Mehta R, Cai X, Lee J, Napoli S, Craven T, Tuazon J, Safdi A, Scialla J, Susztak K, Isakova T. Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes. Kidney Int Rep. 2018 Sep 18;4(1):94-102. doi: 10.1016/j.ekir.2018.09.006. eCollection 2019 Jan.

  PMID: 30596172 BACKGROUND

MeSH Terms

Conditions

Diabetic Nephropathies; Diabetes Mellitus, Type 1

Interventions

Fenofibrate

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones

Study Officials

• Alessandro Doria, MD PhD MPH

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

• Michael Mauer, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Investigator and Professor of Medicine

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: June 18, 2021
• Study Start: January 4, 2022
• Primary Completion: May 1, 2025
• Study Completion (Estimated): October 31, 2026
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be made available two years after completion of the study
• Access Criteria: Access will be governed by the NIDDK repository.

Locations

US (4)