NCT04661358: Protocol AF

A Randomized Clinical Trial Evaluating Fenofibrate for Prevention of Diabetic Retinopathy Worsening

Recruiting now Phase 3 Last updated 11 November 2025

What this trial tests

Phase 3 trial testing Fenofibrate in Diabetic Retinopathy in 560 participants. Currently enrolling.

Timeline

5 March 2021

Primary endpoint
1 December 2029

1 December 2029

Quick facts

Lead sponsor	Jaeb Center for Health Research
Phase	Phase 3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	560
Start date	5 March 2021
Primary completion	1 December 2029
Estimated completion	1 December 2029
Sites	66 locations across United States

Drugs / interventions tested

• Fenofibrate (FENOFIBRATE) — full drug profile →
• Placebo

Conditions studied

• Diabetic Retinopathy — all drugs for Diabetic Retinopathy →

Sponsor

Jaeb Center for Health Research — full company profile →

Who can join

Adults 18 to 80, any sex, with Diabetic Retinopathy. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Worsening of diabetic retinopathy
  Time frame: 6- years
  Defined as * 2 or more step worsening on Early Treatment Diabetic Retinopathy Study (ETDRS) diabetic retinopathy severity on fundus photographs. * Development of neovascularization within the 7-modified ETDRS fields on fluorescein angiography. * Intraocular procedure undertaken to treat diabetic retinopathy including panretinal photocoagulation, intraocular anti-vascular endothelial growth factor

Sponsor's own description

This randomized trial will evaluate the effect of fenofibrate compared with placebo for prevention of diabetic retinopathy (DR) worsening through 6 years of follow-up in eyes with mild to moderately severe non-proliferative DR (NPDR) and no CI-DME at baseline.

In addition to evaluating efficacy, this study aims to evaluate the feasibility of a model for ophthalmologists to prescribe or collaborate with a primary care provider such as an internist/endocrinologist to prescribe and monitor the drug safely. If this study demonstrates that fenofibrate is effective for reducing the onset of proliferative diabetic retinopathy (PDR) or and the results are adopted by the community of retina specialists, a new strategy to prevent vision threatening complications of diabetes could be widely adopted. Widespread use of an oral agent effective at reducing worsening of DR would decrease the numbers of patients who undergo more invasive and much more expensive treatment for DR and who are consequently at risk for side effects that adversely affect visual function. This study will also assess the relationship of glycemic variability, as measured by continuous glucose monitoring with DR outcomes. Ancillary studies will characterize functional and structural outcomes in this cohort.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy.
   Arrigo A, Aragona E, Bandello F. · · 2022 · cited 115× · PMID 35451900 · DOI 10.1080/07853890.2022.2064541
2. Neurovascular Unit: A New Target for Treating Early Stages of Diabetic Retinopathy.
   Simó R, Simó-Servat O, Bogdanov P, Hernández C. · · 2021 · cited 46× · PMID 34452281 · DOI 10.3390/pharmaceutics13081320
3. What else can we do to prevent diabetic retinopathy?
   Simó R, Hernández C. · · 2023 · cited 34× · PMID 37277664 · DOI 10.1007/s00125-023-05940-5
4. New Insights into Treating Early and Advanced Stage Diabetic Retinopathy.
   Simó R, Hernández C. · · 2022 · cited 32× · PMID 35955655 · DOI 10.3390/ijms23158513
5. Visual Function Measurements in Eyes With Diabetic Retinopathy: An Expert Opinion on Available Measures.
   Glassman AR, Elmasry MA, Baskin DE, Brigell M, et al · · 2024 · cited 24× · PMID 38881606 · DOI 10.1016/j.xops.2024.100519
6. Fenofibrate for diabetic retinopathy.
   Kataoka SY, Lois N, Kawano S, Kataoka Y, et al · · 2023 · cited 19× · PMID 37310870 · DOI 10.1002/14651858.cd013318.pub2
7. Effect of Fenofibrate Therapy on Laser Treatment for Diabetic Retinopathy: A Meta-Analysis of Randomized Controlled Trials.
   Preiss D, Spata E, Holman RR, Coleman RL, et al · · 2022 · cited 13× · PMID 34876531 · DOI 10.2337/dc21-1439
8. Frontiers in diabetic retinal disease.
   Torm MEW, Dorweiler TF, Fickweiler W, Levine SR, et al · · 2023 · cited 9× · PMID 36608490 · DOI 10.1016/j.jdiacomp.2022.108386