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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how serine and fenofibrate (a medication used to reduce cholesterol levels) might help individuals with macular telangiectasia type 2 (MacTel), a condition affecting the eyes. Participants will be randomly divided into six groups to receive different combinations of treatments or no treatment, assessing which approach best adjusts certain blood fat levels. The trial will evaluate safety and effectiveness over 10 weeks. Ideal participants have been diagnosed with MacTel in at least one eye and are already part of a related observation study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found fenofibrate to be generally safe for people. It is often used to treat high cholesterol and diabetic retinopathy, an eye condition related to diabetes. Large studies have confirmed its safety.

For serine, the information is less clear. Research suggests caution with serine supplements for MacTel, a specific eye condition, due to complex genetic factors. This does not imply serine is unsafe, but more research is needed.

Regarding the combination of serine and fenofibrate, studies have not shown any specific safety concerns. However, since this is an early phase study, researchers are closely monitoring the treatment for safety. Participants will be observed for any side effects during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to managing Macular Telangiectasia Type 2. Unlike the standard of care, which typically includes dietary supplements, laser treatments, or anti-VEGF injections, these treatments use a combination of Fenofibrate, a lipid-lowering medication, and Serine, an amino acid. Fenofibrate might help due to its anti-inflammatory properties, while Serine is believed to support eye health at a cellular level. This combination targets the condition differently, potentially providing new therapeutic benefits that existing options do not address.

What evidence suggests that this trial's treatments could be effective for macular telangiectasia type 2?

This trial will evaluate the effects of serine and fenofibrate, both individually and in combination, on macular telangiectasia type 2 (MacTel). Research has shown that serine and fenofibrate might help by reducing harmful blood fats linked to eye issues. Studies suggest that taking serine, either alone or with fenofibrate, can normalize blood fat levels. Fenofibrate has proven effective in managing blood fats, potentially benefiting eye health. Serine plays a crucial role in producing certain fats in the body, and disruptions in this process are linked to MacTel. Together, these treatments aim to address the main causes of eye damage in MacTel. ^{1 6 7 8 9}

Who Is on the Research Team?

Mari A Gantner, PhD

Principal Investigator

Lowy Medical Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fenofibrate
• Serine

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-3-telangiectasis-7-2021-16f1a

Serine + Fenofibrate for Macular Telangiectasia Type 2 · ... This trial tests serine and fenofibrate on patients with MacTel to see if they can lower harmful blood fats linked to eye problems.

2. ctv.veeva.com ctv.veeva.com/study/serine-and-fenofibrate-study-in-patients-with-mactel-type2

Serine and Fenofibrate Study in Patients With MacTel Type 2 This is a Phase 2a study of the effect of serine supplementation and fenofibrate treatment on serum deoxysphingolipid levels in patients ...

3. ophthalmologytimes.com ophthalmologytimes.com/view/angiogenesis-2025-encapsulated-cell-therapy-for-mactel-shows-long-term-efficacy-in-phase-3-trials

Angiogenesis 2025: Encapsulated cell therapy for MacTel ... Angiogenesis 2025: Encapsulated cell therapy for MacTel shows long-term efficacy in phase 3 trials. Author(s)Martin Friedlander, MD, PhD ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04907084/serine-and-fenofibrate-study-in-patients-with-mactel-type-2

Serine and Fenofibrate Study in Patients With MacTel Type 2 This is a Phase 2a study of the effect of serine supplementation and fenofibrate treatment on serum deoxysphingolipid levels in patients ...

5. lmri.net lmri.net/research-2/clinical-research/clinical-trials/

Clinical Trials The Lowy Medical Research Institute sponsored a pilot study to test subthreshold photothermal treatment in macular telangiectasia type 2. The purpose of this ...

6. lmri.net lmri.net/mactel-safe-study/

MacTel SAFE Study The study aims to determine the effect of serine and/or fenofibrate on circulating metabolite and lipid levels in patient blood.

7. aao.org aao.org/eyenet/article/metabolic-link-to-mactel-confirmed

Metabolic Link to MacTel Confirmed The researchers cautioned against prescribing fenofibrate or serine supplements to patients with MacTel type 2, “given the complex genetic ...

8. reviewofophthalmology.com reviewofophthalmology.com/article/update-on-macular-telangiectasia-type2-mactel

Update on Macular Telangiectasia Type-2 (MacTel) Macular telangiectasia Type-2 can often present with mild problems with visual acuity as well as retinal changes that can mimic other ...

9. clinicaltrials.gov clinicaltrials.gov/search?cond=%22Telangiectasis%22&intr=%22Fenofibrate%22&viewType=Table&rank=1

Search for: "Telangiectasis", "Fenofibrate" | Card Results Also called a data safety and monitoring board, or DSMB. ... Serine and Fenofibrate Study in Patients With MacTel Type 2. Conditions. Macular Telangiectasia Type ...