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.



Eligible Ages
Between 18 Years and 80 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  • Age ≥18 years and < 80 years. - Type 1 or type 2 diabetes. - At least one eye with the following: - Mild to moderately severe NPDR (defined by ETDRS DR severity level 35 to 47), confirmed by central Reading Center grading of fundus photographs. - Best-corrected E-ETDRS visual acuity letter score of ≥74 (approximate Snellen equivalent 20/32 or better). If best corrected letter score is 74-78, investigator must verify that vision loss is not due to the presence of CI-DME, cataract, or other condition that may affect visual acuity during the course of the study. - If only one eye is eligible, the non-study eye must have at least microaneurysms only (DR severity level 20)

Exclusion Criteria

Eye-level exclusion criteria (the eye is ineligible if any of the following is met): - Current CI-DME based on clinical exam or OCT central subfield thickness (CST) - Zeiss Cirrus: CST ≥290 µm in women or ≥ 305 µm in men - Heidelberg Spectralis: CST ≥305 µm in women or ≥320 µm in men - Any prior treatment for DME or DR, other than focal/grid laser. If the eye has a history of focal/grid laser, it must be at least 12 months prior. - History of intraocular anti-VEGF or corticosteroid treatment within the prior year for any indication Participant-level exclusion criterion (the participant is ineligible if the following criterion is met): • Decreased renal function, defined as requiring dialysis or central laboratory eGFR value < 45 mL/min/1.73 m2

Study Design

Phase 3
Study Type
Intervention Model
Parallel Assignment
Intervention Model Description
Randomized, double-masked, placebo-controlled clinical trial
Primary Purpose
Triple (Participant, Care Provider, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Fenofibrate 160-mg
  • Drug: Fenofibrate
    Participants begin with a dose of either 160mg or 54mg fenofibrate, based on eGFR value at screening, taken once daily with food. The dose may be adjusted during follow-up based on protocol guidelines.
Placebo Comparator
  • Other: Placebo
    Participants begin with a dose of either 160mg or 54mg placebo, based on eGFR value at screening, taken once daily with food. The dose may be adjusted during follow-up based on protocol guidelines.

Recruiting Locations

Boston Medical Center Corporation
Boston, Massachusetts 02118
Steven D. Ness, MD

More Details

Jaeb Center for Health Research

Study Contact

Adam R Glassman, MS


Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.