Fenofibrate for Diabetic Retinopathy

(Protocol AF Trial)

Recruiting at 60 trial locations

Overseen By Adam R Glassman, MS

Age: 18+

Sex: Any

Trial Phase: Phase 3

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 You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 years

560 Participants Needed

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. ^{1 2 3 4 5}

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. ^{4 6 7 8 9}

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. ^{1 2 3 4 5}

Research Team

Emily Y Chew, MD

Principal Investigator

National Institutes of Health (NIH)

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

My non-study eye has minor blood vessel damage.

Your eyesight with glasses or contacts is at least 20/32 or better, unless there are specific eye conditions that might affect your vision.

I have diabetes.

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.

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

Treatment Details

Interventions

• Fenofibrate
• Placebo

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

Jaeb Center for Health Research

Lead Sponsor

Trials

162

Recruited

36,200+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

The Leona M. and Harry B. Helmsley Charitable Trust

Collaborator

Trials

69

Recruited

101,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Roche Pharma AG

Industry Sponsor

Trials

413

Recruited

430,000+

Dr. Thomas Schinecker

Roche Pharma AG

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Pharma AG

Chief Medical Officer since 2019

MD from University of California, San Francisco

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Findings from Research

Fenofibrate has been shown to significantly reduce the need for laser treatment in diabetic retinopathy by 31% and slow disease progression in patients with type 2 diabetes, based on data from two major trials involving 11,388 participants.

The drug's effectiveness is particularly notable in patients with preexisting retinopathy, and its mechanisms of action include improving lipid metabolism, reducing oxidative stress, and providing neuroprotection, suggesting it could be a valuable adjunctive treatment for early diabetic retinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate - a potential systemic treatment for diabetic retinopathy? Wong, TY., Simó, R., Mitchell, P.[2013]

Tight control of glucose and blood pressure is crucial in managing diabetic retinopathy (DR), significantly reducing the risk of its development and progression.

Fenofibrate treatment has been shown to reduce the need for laser treatment for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) by 31%, and it also decreased the progression of retinopathy by 34% compared to placebo, highlighting its potential as an effective therapy in DR management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibrates and statins in the treatment of diabetic retinopathy. Ansquer, JC., Crimet, D., Foucher, C.[2019]

Fenofibrate has been shown to effectively reduce the need for laser therapy and prevent disease progression in patients with pre-existing diabetic retinopathy, as demonstrated in the FIELD study with a daily dose of 200 mg.

In the ACCORD Eye study, fenofibrate combined with simvastatin led to a 40% reduction in the odds of retinopathy progression over 4 years, highlighting its potential benefits for patients with type 2 diabetes, independent of blood glucose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. Wright, AD., Dodson, PM.[2022]

Fenofibrate likely has little to no effect on the progression of diabetic retinopathy (DR) in people with type 2 diabetes, based on a systematic review of two studies involving 15,313 participants over four to five years.

However, in individuals with overt retinopathy, fenofibrate may significantly slow the progression of DR, although it also increases the risk of serious adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate for diabetic retinopathy. Kataoka, SY., Lois, N., Kawano, S., et al.[2023]

Fenofibrate, a safe and affordable medication, has shown significant benefits in reducing the progression of diabetic retinopathy (DR) in patients with type 2 diabetes, as demonstrated in large clinical trials like FIELD and ACCORD.

Despite its efficacy in treating DR, fenofibrate is not commonly prescribed for this condition, partly because retinopathy was not the primary focus of the FIELD and ACCORD studies; new trials are being conducted to specifically evaluate its effects on DR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate for Diabetic Retinopathy. Stewart, S., Lois, N.[2022]

In a study of 32,253 type 2 diabetic patients without previous retinopathy, long-term use of fenofibrate was associated with a 43% reduced risk of developing diabetic retinopathy compared to non-users, indicating its potential efficacy in preventing this condition.

Fenofibrate also significantly decreased the need for laser treatment for diabetic retinopathy, with a 41% lower risk, suggesting it may be an effective intervention for managing complications in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Fenofibrate and Diabetic Retinopathy in Type 2 Diabetic Patients: A Population-Based Retrospective Cohort Study in Taiwan. Lin, YC., Chen, YC., Horng, JT., et al.[2021]

In a study of 9795 patients with type 2 diabetes, those treated with fenofibrate had a significantly lower need for laser treatment for diabetic retinopathy compared to those on placebo (3.4% vs 4.9%), indicating its efficacy in reducing treatment requirements.

While fenofibrate did not significantly affect the overall progression of retinopathy grades, it was particularly effective in preventing worsening in patients with pre-existing retinopathy, showing a notable reduction in 2-step progression compared to placebo (3.1% vs 14.6%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Keech, AC., Mitchell, P., Summanen, PA., et al.[2022]

Fenofibrate significantly reduces the risk of needing laser treatment for diabetic retinopathy, as shown in the FIELD study, highlighting its efficacy in managing this condition in patients with type 2 diabetes.

The ACCORD-Eye study demonstrated that combining fenofibrate with statin therapy leads to a notable reduction in the progression of diabetic retinopathy compared to statin therapy alone, reinforcing the effectiveness of fenofibrate in treating this eye disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of fenofibrate in the management of patients with diabetic retinopathy: an evidence-based review. Sharma, N., Ooi, JL., Ong, J., et al.[2016]

Modified lipoproteins can cause injury to the outer blood-retina barrier (BRB), leading to potential complications in early diabetic retinopathy, as demonstrated in cultured human retinal pigment epithelium cells.

Fenofibric acid, an active metabolite of fenofibrate, was found to protect the outer BRB from damage caused by modified lipoproteins through an AMPK-mediated mechanism, independent of PPARα, suggesting a new therapeutic approach for diabetic retinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Modified Low-Density Lipoproteins and Fenofibrate on an Outer Blood-Retina Barrier Model: Implications for Diabetic Retinopathy. Fu, D., Yu, JY., Connell, AR., et al.[2021]

References

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

Fenofibrate - a potential systemic treatment for diabetic retinopathy? [2013]

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

Fibrates and statins in the treatment of diabetic retinopathy. [2019]

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

Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. [2022]

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

Fenofibrate for diabetic retinopathy. [2023]

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

Fenofibrate for Diabetic Retinopathy. [2022]

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]

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]

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

The use of fenofibrate in the management of patients with diabetic retinopathy: an evidence-based review. [2016]

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]