Serine + Fenofibrate for Macular Telangiectasia Type 2

(SAFE Trial)

Recruiting at 8 trial locations

Overseen By Jennifer Trombley, RN MSN DAOM CCRC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Lowy Medical Research Institute Limited

Must not be taking: Serine, Glycine, Fibrates, Anticoagulants

Disqualifiers: Liver disease, Renal dysfunction, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 11

Duration: 6 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests serine and fenofibrate on patients with MacTel to see if they can lower harmful blood fats linked to eye problems. Fenofibrate is known to reduce bad fats and increase good fats in the blood.

Do I have to stop taking my current medications to join the trial?

Yes, you will need to stop taking certain medications. You cannot participate if you are currently taking serine, glycine supplements, fibrates, anticoagulants, colchicine, cyclosporine, tacrolimus, or bile acid binding resins.

What data supports the effectiveness of the drug Fenofibrate for treating Macular Telangiectasia Type 2?

Research shows that Fenofibrate can reduce abnormal blood vessel growth in the eyes, which is helpful in conditions like diabetic retinopathy and age-related macular degeneration. This suggests it might also help with Macular Telangiectasia Type 2, which involves similar eye issues. ^{1 2 3 4 5}

Is the combination of Serine and Fenofibrate safe for humans?

Fenofibrate, used for conditions like diabetic retinopathy and high cholesterol, is generally considered safe in humans based on large clinical trials. However, specific safety data for the combination of Serine and Fenofibrate is not available. ^{1 3 6 7 8}

How does the drug Serine + Fenofibrate differ from other treatments for Macular Telangiectasia Type 2?

The combination of Serine and Fenofibrate is unique because Fenofibrate, a drug typically used to manage cholesterol levels, has shown potential in improving retinal health by reducing fibrosis and neovascularization (abnormal blood vessel growth) in the eye, which are not typical targets of standard treatments for Macular Telangiectasia Type 2. ^{1 3 9 10 11}

Research Team

Mari A Gantner, PhD

Principal Investigator

Lowy Medical Research Institute

Eligibility Criteria

Inclusion Criteria

Signed and dated written informed consent obtained from the participant in accordance with the local regulations

You are at least 21 years old, regardless of your gender.

You have been diagnosed with MacTel type 2 in at least one eye and are enrolled in the Natural History Observation and Registry Study (NHOR).

Exclusion Criteria

Participant is unable to provide informed consent

Participant is less than 21 years of age

Participant is currently taking, or has taken within four weeks prior to screening, a serine or glycine supplement

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive serine supplementation and/or fenofibrate treatment for 6 weeks

6 weeks

Visits at Week 0, 3, and 6

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Visit at Week 10

Treatment Details

Interventions

• Fenofibrate
• Serine

Participant Groups

Group I: Serine 400 mg/kg/day and Fenofibrate 160 mg/day Experimental Treatment 2 Interventions

Serine 400 mg/kg per day. To be taken once per day for 6 weeks. Exact dose dependent on participant's weight (in kg)). Fenofibrate 160 mg per day. To be taken once per day for 6 weeks.

Group II: Serine 400 mg/kg/day Experimental Treatment 1 Intervention

Serine 400 mg/kg per day. To be taken once per day for 6 weeks. Exact dose dependent on participant's weight (in kg)).

Group III: Serine 200 mg/kg/day and Fenofibrate 160 mg/day Experimental Treatment 2 Interventions

Serine 200 mg/kg per day. To be taken once per day for 6 weeks. Exact dose dependent on participant's weight (in kg)). Fenofibrate 160 mg per day. To be taken once per day for 6 weeks.

Group IV: Serine 200 mg/kg/day Experimental Treatment 1 Intervention

Serine 200 mg/kg per day. To be taken once per day for 6 weeks. Exact dose dependent on participant's weight (in kg)).

Group V: Fenofibrate 160 mg/day Experimental Treatment 1 Intervention

Fenofibrate 160 mg per day. To be taken once per day for 6 weeks.

Group VI: No treatment Active Control 1 Intervention

Control group: no investigational product taken

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?

The Lowy Medical Research Institute Limited

Lead Sponsor

Trials

8

Recruited

430+

Findings from Research

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]

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

Therapeutic Effects of PPARα Agonist on Ocular Neovascularization in Models Recapitulating Neovascular Age-Related Macular Degeneration. [2018]

2. France pubmed.ncbi.nlm.nih.gov

Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis: A meta-analysis. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis. [2022]

4. India pubmed.ncbi.nlm.nih.gov

Efficiency of fenofibrate in facilitating the reduction of central macular thickness in diabetic macular edema. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Fenofibrate for diabetic retinopathy. [2023]

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

Relationship between Using Fibrate and Open-Angle Glaucoma in Hyperlipidemic Patients: A Population-Based Cohort Study. [2022]

7. China pubmed.ncbi.nlm.nih.gov

Fenofibrate for Diabetic Retinopathy. [2022]

8. 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]

9. Ukraine pubmed.ncbi.nlm.nih.gov

[CHANGES OF LIFETIME MORPHOLOGICAL PARAMETERS OF THE RETINA ON THE BACKGROUND OF CORRECTION OF LIPID METABOLISM IN PATIENTSWITH TYPE 2 DIABETES MELLITUS]. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Fenofibrate Inhibits Subretinal Fibrosis Through Suppressing TGF-β-Smad2/3 signaling and Wnt signaling in Neovascular Age-Related Macular Degeneration. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Pemafibrate Prevents Retinal Pathological Neovascularization by Increasing FGF21 Level in a Murine Oxygen-Induced Retinopathy Model. [2020]