Fenofibrate for Diabetic Retinopathy

(Protocol AF Trial)

Recruiting in Palo Alto (17 mi)

+60 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Jaeb Center for Health Research

Must not be taking: Anti-VEGF, Corticosteroids

Disqualifiers: Decreased renal function, CI-DME, others

Stay on Your Current Meds

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What evidence supports the effectiveness of the drug fenofibrate for diabetic retinopathy?

Research shows that fenofibrate can help reduce the progression of diabetic retinopathy, a common eye problem in people with diabetes, by decreasing the need for laser treatments and slowing disease progression. Studies like the FIELD and ACCORD Eye trials found that fenofibrate reduced the risk of retinopathy worsening and helped manage related eye issues.

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Is fenofibrate safe for humans?

Fenofibrate has been studied for its effects on diabetic retinopathy and is generally considered safe for long-term use in humans. However, as with any medication, it may have side effects, and further research is needed to confirm its safety profile.

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How does the drug fenofibrate differ from other treatments for diabetic retinopathy?

Fenofibrate is unique because it is an oral medication that not only helps manage cholesterol levels but also reduces the progression of diabetic retinopathy by decreasing inflammation and improving blood vessel health in the retina. Unlike standard treatments like laser therapy, fenofibrate can prevent the need for such interventions by addressing underlying issues in the eye.

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Eligibility Criteria

Adults aged 18-79 with type 1 or type 2 diabetes and mild to moderately severe non-proliferative diabetic retinopathy (NPDR) in at least one eye can join. They must have good vision (20/32 or better) and no current diabetic macular edema (DME). Those with previous treatments for DME or DR, except certain lasers, poor kidney function, or recent anti-VEGF/corticosteroid eye injections cannot participate.

Inclusion Criteria

It seems like the criterion you provided is incomplete. Can you please provide more details or context so that I can assist you accurately?

I am between 18 and 79 years old.

I am between 18 and 79 years old.

Exclusion Criteria

My kidney function is normal or only mildly reduced, not requiring dialysis.

You have a specific eye condition called CI-DME, based on an eye exam or OCT scan with certain measurements for CST.

I haven't had eye injections for any condition in the last year.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fenofibrate or placebo to evaluate the prevention of diabetic retinopathy worsening

6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

Participant Groups

The trial is testing if fenofibrate can prevent the worsening of diabetic retinopathy over four years compared to a placebo. It's randomized, meaning participants are put into the fenofibrate or placebo group by chance. The study also explores how doctors might safely prescribe this treatment.

Group I: Fenofibrate 160-mg Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Fenofibrate is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Fenofibrate for:

• High cholesterol
• Severe high triglycerides

🇪🇺 Approved in European Union as Fenofibrate for:

• Mixed hyperlipidemia
• Primary hypercholesterolemia
• Severe hypertriglyceridemia

🇨🇦 Approved in Canada as Fenofibrate for:

• Hyperlipidemia
• Hypertriglyceridemia

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Eye Clinic of Wisconsin Wausau, WI

Baylor College of Medicine, Baylor Eye Physicians and Surgeons Houston, TX

The Curators of the University of Missouri Columbia, MO

Austin Research Center for Retina Austin, TX

More Trial Locations

Who Is Running the Clinical Trial?

Jaeb Center for Health Research Lead Sponsor

Juvenile Diabetes Research Foundation Collaborator

The Leona M. and Harry B. Helmsley Charitable Trust Collaborator

National Institutes of Health (NIH) Collaborator

Roche Pharma AG Industry Sponsor

National Eye Institute (NEI) Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Fenofibrate - a potential systemic treatment for diabetic retinopathy? [2013] To review clinical and experimental data for fenofibrate as a possible systemic treatment for diabetic retinopathy.

2. Netherlands pubmed.ncbi.nlm.nih.gov

Fibrates and statins in the treatment of diabetic retinopathy. [2019] Diabetic retinopathy (DR) is one of the leading risk factors and causes of blindness worldwide. Tight glucose and blood pressure control has been shown to significantly decrease the risk of development as well as the progression of retinopathy and represents the cornerstone of medical management of DR. The two most threatening complications of DR are diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Photocoagulation is standard treatment for both DME and PDR. However, some patients suffer permanent visual loss despite therapy. Treatment with fibrates first showed reduction in hard exudates, an effect subsequently shown with statins in short term studies, in particular two randomized studies in patients with macular edema. In the FIELD study which pre-specified microvascular outcomes, fenofibrate reduced laser treatment for DME or PDR by 31%:164 (3.4%) patients on fenofibrate vs. 238 (4.9%) on placebo (p

3. England pubmed.ncbi.nlm.nih.gov

Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. [2022] The approach of all ophthalmologists, diabetologists and general practitioners seeing patients with diabetic retinopathy should be that good control of blood glucose, blood pressure and plasma lipids are all essential components of modern medical management. The more recent data on the use of fenofibrate in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye studies is reviewed. In FIELD, fenofibrate (200 mg/day) reduced the requirements for laser therapy and prevented disease progression in patients with pre-existing diabetic retinopathy. In ACCORD Eye, fenofibrate (160 mg daily) with simvastatin resulted in a 40% reduction in the odds of retinopathy progressing over 4 years, compared with simvastatin alone. This occurred with an increase in HDL-cholesterol and a decrease in the serum triglyceride level in the fenofibrate group, as compared with the placebo group, and was independent of glycaemic control. We believe fenofibrate is effective in preventing progression of established diabetic retinopathy in type 2 diabetes and should be considered for patients with pre-proliferative diabetic retinopathy and/or diabetic maculopathy, particularly in those with macular oedema requiring laser.

4. England pubmed.ncbi.nlm.nih.gov

Fenofibrate for diabetic retinopathy. [2023] Diabetic retinopathy (DR) remains a major cause of sight loss worldwide, despite new therapies and improvements in the metabolic control of people living with diabetes. Therefore, DR creates a physical and psychological burden for people, and an economic burden for society. Preventing the development and progression of DR, or avoiding the occurrence of its sight-threatening complications is essential, and must be pursued to save sight. Fenofibrate may be a useful strategy to achieve this goal, by reversing diabetes' effects and reducing inflammation in the retina, as well as improving dyslipidaemia and hypertriglyceridaemia. OBJECTIVES: To investigate the benefits and harms of fenofibrate for preventing the development and progression of diabetic retinopathy in people with type 1 (T1D) or type 2 diabetes (T2D), compared with placebo or observation.

5. China pubmed.ncbi.nlm.nih.gov

Fenofibrate for Diabetic Retinopathy. [2022] Fenofibrate is a safe and inexpensive orally administered fibric acid derivative conventionally used to treat dyslipidemia. Two large randomized clinical trials, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies, demonstrated the benefit of oral fenofibrate in the treatment of patients with type 2 diabetes and diabetic retinopathy (DR), including reduced disease progression and need for laser treatment for diabetic macular edema and proliferative diabetic retinopathy. These findings are supported by results of experimental studies, which have demonstrated beneficial effects of fenofibrate ameliorating retinal vascular leakage and leukostasis, downregulating vascular endothelial growth factor, and reducing endothelial cell and pericyte loss, among others; all of these are characteristic features of DR. In spite of this evidence, fenofibrate is not prescribed routinely for treating patients with diabetes and DR. In FIELD and ACCORD studies, retinopathy was not the primary outcome and this may explain, at least partly, its lack of use for this indication. New trials are now underway to specifically address the effects of fenofibrate in DR; these trials will provide additional and robust data that may support current evidence favoring the use of fenofibrate in this common microvascular complication of diabetes.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Association of Fenofibrate and Diabetic Retinopathy in Type 2 Diabetic Patients: A Population-Based Retrospective Cohort Study in Taiwan. [2021] Background and Objectives: Fenofibrate, a PPAR-α agonist, has been demonstrated to reduce the progression of diabetic retinopathy (DR) and the need for laser treatment in a FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study. However, in the subgroup of patients without pre-existing DR, there was no significant difference in the progression of DR between the fenofibrate group and the placebo group. In this study, we aim to investigate whether fenofibrate can decrease the risk of incident DR in a population-based cohort study of type 2 diabetic patients in Taiwan. Materials and Methods: A total of 32,253 type 2 diabetic patients without previous retinopathy were retrieved from 892,419 patients in 2001-2002. They were then divided into two groups based on whether they were exposed to fenofibrate or not. The patients were followed until a diagnosis of diabetic retinopathy was made or until the year 2008. Results: With a follow-up period of 6.8 ± 1.5 years and 5.4 ± 2.6 years for 2500 fenofibrate users and 29,753 non-users, respectively, the Cox proportional hazard regression analysis revealed that the hazard ratio (HR) of new onset retinopathy was 0.57 (95% CI 0.57-0.62, p < 0.001). After adjusting for hypertension; the Charlson comorbidity index (CCI); and medications such as angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), anticoagulants, gemfibrozil, statins, and hypoglycemic agents, the adjusted HR was 0.75 (95% CI 0.68-0.82, p < 0.001). The need for laser treatment has an HR and adjusted HR of 0.59 (95% CI 0.49-0.71, p < 0.001) and 0.67 (95% CI 0.56-0.81, p < 0.001), respectively. Conclusion: Our study showed that the long-term and regular use of fenofibrate may decrease the risk of incident retinopathy and the need for laser treatment in type 2 diabetic patients. Since there are limitations associated with our study, further investigations are necessary to confirm such an association.

7. England pubmed.ncbi.nlm.nih.gov

Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. [2022] Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects. Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus.

8. Australia pubmed.ncbi.nlm.nih.gov

The use of fenofibrate in the management of patients with diabetic retinopathy: an evidence-based review. [2016] Diabetic retinopathy is a significant cause of vision impairment, especially affecting those of working age. There are two large, randomised controlled trials examining the effect of fenofibrate on diabetic retinopathy.

9. United States pubmed.ncbi.nlm.nih.gov

Effects of Modified Low-Density Lipoproteins and Fenofibrate on an Outer Blood-Retina Barrier Model: Implications for Diabetic Retinopathy. [2021] Purpose: There is a lack of treatment for early diabetic retinopathy (DR), including blood-retina barrier (BRB) breakdown. The robust clinical benefit of fenofibrate in DR provides an opportunity to explore disease mechanisms and therapeutic targets. We have previously found that modified lipoproteins contribute to DR and that fenofibrate protects the inner BRB. We now investigate (1) whether modified lipoproteins elicit outer BRB injury and (2) whether fenofibrate may alleviate such damage. Methods: Human retinal pigment epithelium ARPE-19 cells were cultured in semipermeable transwells to establish a monolayer barrier and then exposed to heavily oxidized, glycated low-density lipoprotein (HOG-LDL, 25-300 mg/L, up to 24 h) versus native (N)-LDL. Transepithelial electric resistance (TEER) and FITC-dextran permeability were measured. The effects of fenofibrate, its active metabolite fenofibric acid, and other peroxisome proliferator-activated receptor (PPARα) agonists (gemfibrozil, bezafibrate, and WY14643) were evaluated, with and without the PPARα antagonist GW6471 or the adenosine monophosphate-activated protein kinase (AMPK) inhibitor Compound C. Results: HOG-LDL induced concentration- and time-dependent barrier impairment, decreasing TEER and increasing dextran leakage, effects that were amplified by high glucose. Fenofibric acid, but not fenofibrate, gemfibrozil, bezafibrate, or WY14643, attenuated barrier impairment. This effect was reversed significantly by Compound C, but not by GW6471. Conclusions: Modified lipoproteins elicited outer BRB injury in an experimental model, which was reduced by fenofibric acid through a PPARα-independent, AMPK-mediated mechanism. These findings suggest a protective role of fenofibric acid on the outer BRB in diabetic retina.