Protocol AF: Fenofibrate for Prevention of DR Worsening

Sponsor
Jaeb Center for Health Research (Other)
Overall Status
Recruiting
CT.gov ID
NCT04661358
Collaborator
National Institutes of Health (NIH) (NIH), National Eye Institute (NEI) (NIH), Juvenile Diabetes Research Foundation (Other), Roche Pharma AG (Industry), The Leona M. and Harry B. Helmsley Charitable Trust (Other)
910
Enrollment
29
Locations
2
Arms
72.9
Anticipated Duration (Months)
31.4
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized trial will evaluate the effect of fenofibrate compared with placebo for prevention of diabetic retinopathy (DR) worsening through 4 years of follow-up in participants 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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Fenofibrate 160mg
  • Other: Placebo
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
910 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized, double-masked, placebo-controlled clinical trialRandomized, double-masked, placebo-controlled clinical trial
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized Clinical Trial Evaluating Fenofibrate for Prevention of Diabetic Retinopathy Worsening
Actual Study Start Date :
Mar 5, 2021
Anticipated Primary Completion Date :
Apr 1, 2027
Anticipated Study Completion Date :
Apr 1, 2027

Arms and Interventions

ArmIntervention/Treatment
Experimental: Fenofibrate 160-mg

Drug: Fenofibrate 160mg
Participants begin with a dose of 160mg fenofibrate taken once daily with food. The dose may be adjusted during follow-up based on protocol guidelines.

Placebo Comparator: Placebo

Other: Placebo
Participants begin with a dose of 160mg placebo taken once daily with food. The dose may be adjusted during follow-up based on protocol guidelines.

Outcome Measures

Primary Outcome Measures

  1. Worsening of diabetic retinopathy [4- years]

    Defined as 3 or more step worsening in person-level Early Treatment Diabetic Retinopathy Study (ETDRS) diabetic retinopathy severity on fundus photographs. Development of neovascularization within the 7-modified ETDRS fields on fluorescein angiography in either eye. Intraocular procedure undertaken to treat diabetic retinopathy in either eye including panretinal photocoagulation, intraocular anti-vascular endothelial growth factor, corticosteroid, or vitrectomy.

Secondary Outcome Measures

  1. Intraocular procedure undertaken to treat diabetic retinopathy or diabetic macular edema in either eye including PRP, intraocular anti-VEGF, corticosteroid, focal/grid laser or vitrectomy [4 years]

  2. Development of CI-DME in either eye [4 years]

    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)Non-topical DME treatment including focal/grid laser, intraocular anti-VEGF, intraocular corticosteroid, or vitrectomy

  3. Development of center-involved diabetic macular edema with vision loss in either eye [4 years]

    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, non-topical DME or 2) treatment including focal/grid laser, intraocular anti-VEGF, intraocular corticosteroid, or vitrectomy

  4. Visual acuity loss from any cause [4 years]

    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 in either eye regardless of whether vision loss is presumed to be from DME or any other cause in either eye

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
  • Inclusion Criteria
  1. Age >= 18 and < 80 years

• Individuals <18 years old are not being included because DR is so rare in this age group that the diagnosis of NPDR may be questionable. Individuals ≥80 years old are excluded to limit co-morbidities and mortality over this long-term trial.

  1. Diagnosis of diabetes mellitus (type 1 or type 2)

• Any one of the following will be considered to be sufficient evidence that diabetes is present, current regular use of insulin for the treatment of diabetes, current regular use of oral anti hyperglycemia agents for the treatment of diabetes, or documented diabetes by American Diabetes Association and/or the World Health Organization criteria.

  1. Both eyes meet the study eye criteria listed below.

  2. Able and willing to provide informed consent.

  3. Able and willing to wear a continuous glucose monitoring (CGM) device (for United States participants only).

  • Eye level inclusion criteria:
  1. Either (1) both eyes have mild to moderately severe NPDR (defined by ETDRS DR severity level 35 to 47) or (2) one eye has mild to moderately severe NPDR and the other eye has microaneurysms only (DR severity level 20).
  • Confirmation of DR severity level is required by both the investigator and central Reading Center grading of fundus photographs.
  1. Both eyes must have best-corrected E-ETDRS visual acuity letter score ≥79 (approximate Snellen equivalent 20/25 or better) 8. Both eyes must have media clarity, pupillary dilation, and study participant cooperation sufficient to obtain adequate fundus photographs, fluorescein angiogram, and OCT.
  • Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality (including segmentation line placement)

  • Exclusion Criteria

  1. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status that may preclude successful completion of follow-up).

  2. Initiation of intensive insulin treatment (a pump or multiple daily injections) within 3 months prior to screening or plans to do so in the next 3 months.

  3. Participation in an investigational trial that involved treatment within 30 days of screening with any drug that has not received regulatory approval for the indication being studied.

  4. Known allergy or hypersensitivity to any component of fenofibrate.

  5. Known allergy to fluorescein dye.

  6. History of treatment with a prescription fibrate medication (e.g. bezafibrate, fenofibrate, gemfibrozil, fenofibric acid) within 12 months prior to screening or anticipated need for fibrate medication for another indication (e.g. lipid management).

  7. Any prior systemic treatment for DME or DR.

  8. Decreased renal dysfunction, defined as requiring dialysis or central laboratory eGFR value < 60

  9. Active liver disease, defined as any liver function test >3x upper limit of normal based on central laboratory value.

  10. Pre-existing symptomatic gallbladder disease including gallstones; however, prior gallbladder removal is not an exclusion.

  11. Triglycerides >400mg/dL on treatment or >700mg/dL on no treatment based on central laboratory value.

  12. Current use of any of the following medications:

  • Coumarin anticoagulants (Coumadin/Warfarin).

  • Immunosuppressants that affect kidney function, such as cyclosporine and tacrolimus

  • Colchicine (Colcrys)

  1. History of severe myalgia requiring discontinuation of lipid lowering treatment.

  2. Blood pressure > 160/100 (systolic above 160 or diastolic above 100).

  3. HbA1c > 11.0% based on central laboratory value or if lab sample cannot be analyzed, recent result within 3 months

  4. Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to screening or anticipated use during the study.

  5. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 4 years.

  6. Participant is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the next four years.

The following exclusions apply to both eyes:
  1. Evidence of definite neovascularization according to the investigator or central Reading Center grading of fluorescein angiography.

• Includes presence of neovascularization (NV) outside of the 7-modified ETDRS fields on ultra-widefield imaging, which is an exclusion.

  1. Current CI-DME based on clinical exam or OCT central subfield thickness (CST), defined as:
  • Zeiss Cirrus: CST ≥290 µm in women or ≥ 305 µm in men.

  • Heidelberg Spectralis: CST ≥ 305 µm in women or ≥320 µm in men.

  1. Major non-diabetic intraocular pathology that in the opinion of the investigator would substantially and adversely affect visual acuity or lead to ocular neovascularization during the study.

  2. Any prior treatment for DME or DR.

  3. History of major ocular surgery within prior 4 months or anticipated within the next 6 months following randomization.

  4. Anticipated need for intraocular anti-VEGF or PRP in the next 6 months following randomization.

  5. History of intraocular anti-VEGF or corticosteroid treatment within the prior year for any indication.

  6. Any history of vitrectomy.

  7. History of YAG capsulotomy performed within 2 months prior to screening.

  8. Aphakia.

  9. Evidence of uncontrolled glaucoma (intraocular pressure must be <30, with no more than one topical glaucoma medication, and no documented glaucomatous field loss for the eye to be eligible)

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Kent W. Small, MD, AMCGlendaleCaliforniaUnited States91203-1971
2Loma Linda UniversityLoma LindaCaliforniaUnited States92354
3National Ophthalmic Research InstituteFort MyersFloridaUnited States33912
4Florida Retina Institute, James A. Staman, MD, PA- JacksonvilleJacksonvilleFloridaUnited States32216
5Florida Retina ConsultantsLakelandFloridaUnited States33805
6Retina Vitreous Consultants, LLPSarasotaFloridaUnited States34233-1261
7Sarasota Retina InstituteSarasotaFloridaUnited States34239
8Marietta Eye ClinicMariettaGeorgiaUnited States30060
9Thomas Eye GroupSandy SpringsGeorgiaUnited States30328
10Illinois Retina Associates SC - Oak Park SiteOak ParkIllinoisUnited States60304
11John Kenyon American Eye Institute, LLCNew AlbanyIndianaUnited States47150
12Wolfe Eye Clinic-Cedar RapidsHiawathaIowaUnited States52233
13Elman Retina Group, P.A.BaltimoreMarylandUnited States21237
14Joslin Diabetes CenterBostonMassachusettsUnited States02215
15Henry Ford Health SystemDetroitMichiganUnited States48202-2689
16Retina Center, PA DBA Retina Center of MinnesotaMinneapolisMinnesotaUnited States55404
17Retina Research Institute, LLCSaint LouisMissouriUnited States63128-1729
18Retina-Vitreous Surgeons of Central NY, PCLiverpoolNew YorkUnited States13088
19Retina Associates of Western NY, P.C.RochesterNew YorkUnited States14620-4655
20Pamela Weber, MD/Island RetinaShirleyNew YorkUnited States11967
21Dean A. McGee Eye InstituteOklahoma CityOklahomaUnited States73104
22Verum Research LLCEugeneOregonUnited States97401
23Retina Consultants, LLCSalemOregonUnited States97302
24Retina-Vitreous Consultants, Inc.MonroevillePennsylvaniaUnited States15146
25Southeastern Retina Associates, P.C.KnoxvilleTennesseeUnited States37922
26Retina Consultants of Texas, PABellaireTexasUnited States77401
27Baylor College of Medicine, Baylor Eye Physicians and SurgeonsHoustonTexasUnited States77030-4101
28Texas Retina AssociatesLubbockTexasUnited States79424
29Retinal Consultants of San AntonioSan AntonioTexasUnited States78240

Sponsors and Collaborators

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

Investigators

  • Study Chair: Emily Y Chew, MD, National Institutes of Health (NIH)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Jaeb Center for Health Research
ClinicalTrials.gov Identifier:
NCT04661358
Other Study ID Numbers:
  • DRCR.net Protocol AF
  • U10EY014231
First Posted:
Dec 10, 2020
Last Update Posted:
Nov 19, 2021
Last Verified:
Nov 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Jaeb Center for Health Research
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 19, 2021