NCT04661358

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
560

participants targeted

Target at P75+ for phase_3

Timeline
43mo left

Started Mar 2021

Longer than P75 for phase_3

Geographic Reach
1 country

66 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress59%
Mar 2021Dec 2029

First Submitted

Initial submission to the registry

December 3, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

December 10, 2020

Completed
3 months until next milestone

Study Start

First participant enrolled

March 5, 2021

Completed
8.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2029

Last Updated

November 13, 2025

Status Verified

September 1, 2025

Enrollment Period

8.7 years

First QC Date

December 3, 2020

Last Update Submit

November 11, 2025

Conditions

Keywords

Fenofibratenon-proliferative diabetic retinopathy

Outcome Measures

Primary Outcomes (1)

  • Worsening of diabetic retinopathy

    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, corticosteroid, or vitrectomy.

    6- years

Secondary Outcomes (4)

  • Intraocular procedure undertaken to treat diabetic retinopathy or diabetic macular edema including PRP, intraocular anti-VEGF, corticosteroid, focal/grid laser or vitrectomy

    6 years

  • Development of CI-DME

    6 years

  • Development of center-involved diabetic macular edema with vision loss

    6 years

  • Visual acuity loss from any cause

    6 years

Study Arms (2)

Fenofibrate 160-mg

EXPERIMENTAL
Drug: Fenofibrate

Placebo

PLACEBO COMPARATOR
Other: Placebo

Interventions

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.

Fenofibrate 160-mg
PlaceboOTHER

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.

Placebo

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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
  • Decreased renal function, defined as requiring dialysis or central laboratory eGFR value \< 45 mL/min/1.73 m2

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (66)

Kent W. Small, MD, AMC

Glendale, California, 91203-1971, United States

RECRUITING

Salehi Retina Institute Inc.

Huntington Beach, California, 92647-8693, United States

RECRUITING

Loma Linda University

Loma Linda, California, 92354, United States

RECRUITING

UCLA Stein Eye Institute

Pasadena, California, 91103, United States

RECRUITING

Regents of the University of California, Davis, DBA University of California, Davis

Sacramento, California, 95817, United States

RECRUITING

The Regents of the University of California, San Francisco

San Francisco, California, 94110, United States

RECRUITING

National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

RECRUITING

University of Florida- Jacksonville

Jacksonville, Florida, 32209, United States

RECRUITING

Florida Retina Institute, James A. Staman, MD, PA- Jacksonville

Jacksonville, Florida, 32216, United States

RECRUITING

Florida Retina Consultants

Lakeland, Florida, 33805, United States

RECRUITING

Florida Retina Institute, James A. Staman, MD, PA- Orlando

Orlando, Florida, 32806-1101, United States

RECRUITING

Southeast Eye Institute, P.A. dba Eye Associates of Pinellas

Pinellas Park, Florida, 33782, United States

RECRUITING

Retina Vitreous Consultants, LLP

Sarasota, Florida, 34233-1261, United States

RECRUITING

Sarasota Retina Institute

Sarasota, Florida, 34239, United States

RECRUITING

SEASHORE RETINA LLC DBA Retina Specialists of Tampa

Wesley Chapel, Florida, 33544, United States

RECRUITING

Southeast Retina Center, P.C.

Augusta, Georgia, 30909, United States

RECRUITING

Marietta Eye Clinic

Marietta, Georgia, 30060, United States

RECRUITING

Thomas Eye Group

Sandy Springs, Georgia, 30328, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

UIC - Dept of Ophthalmology & Visual Sciences

Chicago, Illinois, 60612, United States

RECRUITING

Illinois Retina Associates SC - Oak Park Site

Oak Park, Illinois, 60304, United States

RECRUITING

Midwest Eye Institute

Indianapolis, Indiana, 46290, United States

RECRUITING

John Kenyon American Eye Institute, LLC

New Albany, Indiana, 47150, United States

RECRUITING

Wolfe Eye Clinic-Cedar Rapids

Hiawatha, Iowa, 52233, United States

RECRUITING

Wolfe Clinic, P.C.- West Des Moines

West Des Moines, Iowa, 50266-7705, United States

RECRUITING

Mid-America Retina Consultants, P.A.

Overland Park, Kansas, 66211, United States

RECRUITING

University of Kansas Medical Center Research Institute, Inc.

Prairie Village, Kansas, 66208, United States

RECRUITING

Joseph E. Humble and Raymond Haik PTRS DBA Eye Assoc of Northeast Louisiana

West Monroe, Louisiana, 71291-4452, United States

RECRUITING

Elman Retina Group, P.A.

Baltimore, Maryland, 21237, United States

RECRUITING

Valley Eye Physicians and Surgeons

Ayer, Massachusetts, 01432, United States

RECRUITING

Boston Medical Center Corporation

Boston, Massachusetts, 02118, United States

RECRUITING

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202-2689, United States

RECRUITING

Foundation for Vision Research and Retina Specialists of Michigan, P.C.

Grand Rapids, Michigan, 49546, United States

RECRUITING

Vitreo-Retinal Associates

Grand Rapids, Michigan, 49546, United States

RECRUITING

Retina Center, PA DBA Retina Center of Minnesota

Minneapolis, Minnesota, 55404, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

The Curators of the University of Missouri

Columbia, Missouri, 65201-5276, United States

RECRUITING

Washington University Ophthalmology

St Louis, Missouri, 63110, United States

RECRUITING

Retina Research Institute, LLC

St Louis, Missouri, 63128-1729, United States

RECRUITING

Retina-Vitreous Surgeons of Central NY, PC

Liverpool, New York, 13088, United States

RECRUITING

MaculaCare

New York, New York, 10021, United States

RECRUITING

Retina Associates of Western NY, P.C.

Rochester, New York, 14620-4655, United States

RECRUITING

Pamela Weber, MD/Island Retina

Shirley, New York, 11967, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27517, United States

RECRUITING

The Cleveland Clinic Foundation DBA Cleveland Clinic Lerner College of Medicine

Cleveland, Ohio, 44120, United States

RECRUITING

Dean A. McGee Eye Institute

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Verum Research LLC

Eugene, Oregon, 97401, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Retina Consultants, LLC

Salem, Oregon, 97302, United States

RECRUITING

Cascade Medical Research Institute, LLC

Springfield, Oregon, 97477, United States

RECRUITING

Retina-Vitreous Consultants, Inc.

Monroeville, Pennsylvania, 15146, United States

RECRUITING

Pittsburg Clinical Trial Consortium

Sewickley, Pennsylvania, 15143, United States

RECRUITING

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, 37922, United States

RECRUITING

Vanderbilt Eye Institute

Nashville, Tennessee, 37232, United States

RECRUITING

Austin Research Center for Retina

Austin, Texas, 78705, United States

RECRUITING

Austin Retina Associates

Austin, Texas, 78705, United States

RECRUITING

Retina Consultants of Texas

Beaumont, Texas, 77707, United States

RECRUITING

Retina Consultants of Texas, PA

Bellaire, Texas, 77401, United States

RECRUITING

Baylor College of Medicine, Baylor Eye Physicians and Surgeons

Houston, Texas, 77030-4101, United States

RECRUITING

Texas Retina Associates

Lubbock, Texas, 79424, United States

RECRUITING

Retinal Consultants of San Antonio

San Antonio, Texas, 78240, United States

RECRUITING

University of Washington

Seattle, Washington, 98104, United States

RECRUITING

Gunderson Health System

La Crosse, Wisconsin, 54601, United States

RECRUITING

Eye Clinic of Wisconsin

Wausau, Wisconsin, 54403, United States

RECRUITING

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

Fenofibrate

Condition Hierarchy (Ancestors)

Retinal DiseasesEye DiseasesDiabetic AngiopathiesVascular DiseasesCardiovascular DiseasesDiabetes ComplicationsDiabetes MellitusEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Fibric AcidsIsobutyratesButyratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsPhenyl EthersEthersBenzophenonesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPhenolsKetones

Study Officials

  • Emily Y Chew, MD

    National Institutes of Health (NIH)

    STUDY CHAIR

Central Study Contacts

Adam R Glassman, MS

CONTACT

Emily Chew, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomized, double-masked, placebo-controlled clinical trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 3, 2020

First Posted

December 10, 2020

Study Start

March 5, 2021

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2029

Last Updated

November 13, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations