Fenofibrate for Prevention of DR Worsening

Diabetic Retinopathy Clinical Trial

— Protocol AF  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04661358
• Other study ID #: DRCR.net Protocol AF
• Secondary ID: U10EY014231
• Status: Recruiting
• Phase: Phase 3
• Start date: March 5, 2021
• Est. completion date: April 2029

Study information

• Verified date: March 2024
• Source: Jaeb Center for Health Research
• Contact: Adam R Glassman, MS
• Phone: 813-975-8690
• Email: drcrnet[@]jaeb.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 560
• Est. completion date: April 2029
• Est. primary completion date: April 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Key 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)

Key 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

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Retinal Diseases

Intervention

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.

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.

Locations

Country	Name	City	State
United States	Southeast Retina Center, P.C.	Augusta	Georgia
United States	Austin Research Center for Retina	Austin	Texas
United States	Austin Retina Associates	Austin	Texas
United States	Valley Eye Physicians and Surgeons	Ayer	Massachusetts
United States	Elman Retina Group, P.A.	Baltimore	Maryland
United States	Retina Consultants of Texas, PA	Bellaire	Texas
United States	Boston Medical Center Corporation	Boston	Massachusetts
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	The Cleveland Clinic Foundation DBA Cleveland Clinic Lerner College of Medicine	Cleveland	Ohio
United States	The Curators of the University of Missouri	Columbia	Missouri
United States	Henry Ford Health System	Detroit	Michigan
United States	Verum Research LLC	Eugene	Oregon
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Kent W. Small, MD, AMC	Glendale	California
United States	Foundation for Vision Research and Retina Specialists of Michigan, P.C.	Grand Rapids	Michigan
United States	Vitreo-Retinal Associates	Grand Rapids	Michigan
United States	Wolfe Eye Clinic-Cedar Rapids	Hiawatha	Iowa
United States	Baylor College of Medicine, Baylor Eye Physicians and Surgeons	Houston	Texas
United States	Salehi Retina Institute Inc.	Huntington Beach	California
United States	Midwest Eye Institute	Indianapolis	Indiana
United States	Florida Retina Institute, James A. Staman, MD, PA- Jacksonville	Jacksonville	Florida
United States	University of Florida- Jacksonville	Jacksonville	Florida
United States	Southeastern Retina Associates, P.C.	Knoxville	Tennessee
United States	Gunderson Health System	La Crosse	Wisconsin
United States	Florida Retina Consultants	Lakeland	Florida
United States	Retina-Vitreous Surgeons of Central NY, PC	Liverpool	New York
United States	Loma Linda University	Loma Linda	California
United States	Texas Retina Associates	Lubbock	Texas
United States	Marietta Eye Clinic	Marietta	Georgia
United States	Retina Center, PA DBA Retina Center of Minnesota	Minneapolis	Minnesota
United States	Retina-Vitreous Consultants, Inc.	Monroeville	Pennsylvania
United States	Vanderbilt Eye Institute	Nashville	Tennessee
United States	John Kenyon American Eye Institute, LLC	New Albany	Indiana
United States	MaculaCare	New York	New York
United States	Illinois Retina Associates SC - Oak Park Site	Oak Park	Illinois
United States	Dean A. McGee Eye Institute	Oklahoma City	Oklahoma
United States	Florida Retina Institute, James A. Staman, MD, PA- Orlando	Orlando	Florida
United States	Mid-America Retina Consultants, P.A.	Overland Park	Kansas
United States	Southeast Eye Institute, P.A. dba Eye Associates of Pinellas	Pinellas Park	Florida
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Retina Associates of Western NY, P.C.	Rochester	New York
United States	Regents of the University of California, Davis, DBA University of California, Davis	Sacramento	California
United States	Retina Research Institute, LLC	Saint Louis	Missouri
United States	Retina Consultants, LLC	Salem	Oregon
United States	Retinal Consultants of San Antonio	San Antonio	Texas
United States	The Regents of the University of California, San Francisco	San Francisco	California
United States	Thomas Eye Group	Sandy Springs	Georgia
United States	Retina Vitreous Consultants, LLP	Sarasota	Florida
United States	Sarasota Retina Institute	Sarasota	Florida
United States	University of Washington	Seattle	Washington
United States	Pittsburg Clinical Trial Consortium	Sewickley	Pennsylvania
United States	Pamela Weber, MD/Island Retina	Shirley	New York
United States	Cascade Medical Research Institute, LLC	Springfield	Oregon
United States	SEASHORE RETINA LLC DBA Retina Specialists of Tampa	Wesley Chapel	Florida
United States	Wolfe Clinic, P.C.- West Des Moines	West Des Moines	Iowa
United States	Joseph E. Humble and Raymond Haik PTRS DBA Eye Assoc of Northeast Louisiana	West Monroe	Louisiana

Sponsors (6)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	Juvenile Diabetes Research Foundation, National Eye Institute (NEI), National Institutes of Health (NIH), Roche Pharma AG, The Leona M. and Harry B. Helmsley Charitable Trust

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Intraocular procedure undertaken to treat diabetic retinopathy or diabetic macular edema including PRP, intraocular anti-VEGF, corticosteroid, focal/grid laser or vitrectomy		6 years
Secondary	Development of CI-DME	Defined as, either 1) at least a 10% increase in OCT central subfield thickness from baseline, OCT central subfield thickness greater than sex and machine-specific threshold values (Zeiss Cirrus: CST =290 µm in women or = 305 µm in men; Heidelberg Spectralis: CST =305 µm in women or =320 µm in men), and Investigator determination that thickening cannot be attributed to any cause other than CI-DME, or 2)Intraocular DME treatment including focal/grid laser, intraocular anti-VEGF, intraocular corticosteroid, or vitrectomy	6 years
Secondary	Development of center-involved diabetic macular edema with vision loss	Defined as either 1) an increase in OCT central subfield thickness of 10% or more from baseline, OCT central subfield thickness greater than sex and machine-specific threshold values (Zeiss Cirrus: CST =290 µm in women or = 305 µm in men; Heidelberg Spectralis: CST =305 µm in women or =320 µm in men), investigator determination that thickening cannot be attributed to any cause other than DME, and a decrease in visual acuity from baseline of 10 or more letters at a single visit or 5 to 9 letters at 2 consecutive visits at least 21 days apart with vision loss presumed to be from DME, intraocular DME or 2) treatment including focal/grid laser, anti-VEGF, corticosteroid injection, or vitrectomy	6 years
Secondary	Visual acuity loss from any cause	Defined as a decrease in visual acuity from baseline of 10 or more letters at a single visit or a 5 to 9-letter decrease at 2 consecutive visits at least 21 days apart regardless of whether vision loss is presumed to be from DME or any other cause	6 years