NAC Eye Drops for Fuchs' Dystrophy

Overseen By Michael Cheung, MSc, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts Eye and Ear Infirmary

Must not be taking: N-Acetylcysteine

Disqualifiers: Pregnancy, Prior eye surgery, others

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

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests eye drops containing N-acetyl cysteine (NAC) to determine their effectiveness in protecting and improving eye health in individuals with Fuchs' Dystrophy, a condition affecting the cornea that can lead to vision problems. The researchers aim to discover if the eye drops can reduce oxidative stress, potentially aiding corneal healing. Participants will receive either a 10% or 20% NAC solution or a placebo. Suitable candidates have advanced Fuchs' Dystrophy and cataracts affecting their vision and are scheduled for specific eye surgery. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You may need to stop using certain eye medications, except for lubricants, hyperosmotic agents, or ocular hypotensive agents. If you're using N-Acetylcysteine in any form, you'll need to stop at least 30 days before joining the trial.

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

Research has shown that N-acetyl cysteine (NAC) eye drops, in both 10% and 20% strengths, are generally safe and well-tolerated. Studies have found that NAC is often used in eye treatments for conditions like dry eye and meibomian gland dysfunction, with a good safety record. Although specific safety data for these solutions in Fuchs' Dystrophy is lacking, NAC's broader use in eye care suggests it is safe for most people. No major reports of side effects have emerged in these cases, offering reassurance to potential trial participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NAC eye drops for Fuchs' Dystrophy because they offer a novel approach by using N-acetyl cysteine (NAC), an antioxidant that targets oxidative stress, a key factor in the progression of this condition. Unlike traditional treatments which mainly focus on managing symptoms, NAC eye drops aim to address the underlying oxidative damage to corneal cells. With concentrations of 10% and 20% being tested, this treatment could provide a more effective and direct method to protect and potentially restore corneal health. Additionally, NAC is well-tolerated and has been used in other eye conditions, making it a promising candidate for improving outcomes in Fuchs' Dystrophy.

What evidence suggests that this trial's treatments could be effective for Fuchs' Dystrophy?

Research has shown that N-acetyl cysteine (NAC) eye drops protect eye cells by reducing damage from harmful molecules, known as oxidative stress. Studies have found that NAC improves the survival of corneal endothelial cells, which are crucial for clear vision. This is particularly beneficial for conditions like Fuchs' Dystrophy, where these cells are at risk. In this trial, researchers are testing both 10% and 20% NAC eye drop solutions in separate treatment arms for their protective effects. Early results suggest that these drops are well-tolerated and may improve eye health by managing oxidative stress. ^{1 2 3 5 6}

Who Is on the Research Team?

Ula Jurkunas, MD

Principal Investigator

Mass Eye and Ear

Are You a Good Fit for This Trial?

This trial is for adults over 21 with advanced Fuchs' Endothelial Corneal Dystrophy (FECD) and cataracts needing surgery. Participants must be able to follow the medication plan and not be pregnant, breastfeeding, or unwilling to use birth control. They shouldn't have had previous eye surgeries in the study eye or used certain medications recently.

Inclusion Criteria

I need surgery for a cornea transplant and cataract removal at the same time.

I am 21 years old or older.

Written informed consent obtained from subject and ability for subject to comply with the requirements of the study

Exclusion Criteria

I use eye medication, but only for dryness, swelling, or pressure.

I have a history of serious eye conditions affecting the cornea.

Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study

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 self-administer NAC or placebo eye drops four times a day for 28 days prior to planned surgery

4 weeks

Weekly check-ins (virtual or in-person)

Surgery

Participants undergo DMEK and cataract surgery, with collection of aqueous fluid and corneal tissue for analysis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery, including assessment of adverse events and corneal measurements

2-3 weeks

2-3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• N-acetyl cysteine (NAC) 10% solution
• N-acetyl cysteine (NAC) 20% solution
• Visine Dry Eye Relief eye drops

Trial Overview The study tests if N-acetyl cysteine (NAC) eye drops can reduce oxidative stress and protect cells in patients with FECD. It compares Visine Dry Eye Relief drops, NAC 10% solution, and NAC 20% solution applied topically before corneal surgery.

How Is the Trial Designed?

Group I: NAC 20% group Active Control 1 Intervention

Subjects in this group will be treated with eye drops containing a 20% solution of N-acetyl cysteine. Topical NAC is a well-tolerated medication that has many applications in ophthalmology including dry eye disease and meibomian gland dysfunction.

Group II: NAC 10% group Active Control 1 Intervention

Subjects in this group will be treated with eye drops containing a 10% solution of N-acetyl cysteine. Topical NAC is a well-tolerated medication that has many applications in ophthalmology including dry eye disease and meibomian gland dysfunction.

Group III: Placebo group Placebo Group 1 Intervention

Subjects in this group will be treated with a placebo (Visine Tears Dry Eye Relief artificial tears ophthalmic solution.)

N-acetyl cysteine (NAC) 10% solution is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Acetylcysteine for:

• Mucolytic agent
• Acetaminophen antidote
• Dry eye disease

Approved in European Union as N-acetyl cysteine for:

• Mucolytic agent
• Paracetamol overdose
• Dry eye disease

Approved in Canada as Acetylcysteine for:

• Mucolytic agent
• Acetaminophen antidote

Who Is Running the Clinical Trial?

Massachusetts Eye and Ear Infirmary

Lead Sponsor

Trials

115

Recruited

15,000+

Published Research Related to This Trial

In a study involving 12 hemodialysis patients, intravenous administration of 2 g of N-acetylcysteine (NAC) over 3 hours was found to be safe, with no observed side effects during the six dialysis sessions.

NAC reached a steady state concentration after the fourth infusion, indicating effective pharmacokinetics in dialysis patients, with a significant dialytic clearance of 5.52 l/h.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients. Soldini, D., Zwahlen, H., Gabutti, L., et al.[2018]

In a study involving 79 eyes of 40 patients with chronic posterior blepharitis, N-acetylcysteine (NAC) significantly improved the fluorescein break-up time (FBUT) and mucous fern pattern, indicating enhanced tear stability and eye surface health.

The mechanism of action for NAC in this context is believed to involve the blocking of lipid peroxidation, which may help alleviate symptoms of chronic blepharitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine in chronic blepharitis. Yalçin, E., Altin, F., Cinhüseyinoglue, F., et al.[2019]

N-acetylcysteine (NAC) is a powerful antioxidant that helps protect cells from oxidative stress by boosting levels of glutathione (GSH), which is crucial for cellular defense against damage.

NAC has a variety of clinical applications, including treating respiratory diseases, serving as an antidote for acetaminophen poisoning, and showing potential benefits in neuropsychiatric disorders by modulating glutamate levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress. Raghu, G., Berk, M., Campochiaro, PA., et al.[2022]

Contact lenses can effectively release therapeutic agents N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) over a 72-hour period, with varying release rates depending on the lens type.

The Frequency 55 lenses demonstrated the highest release rates, with 95.9% of NAC and 60.0% of NACA released within 24 hours, suggesting they are suitable for drug delivery during wear, although NACA was released in smaller amounts due to its more hydrophobic nature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Release of N-acetylcysteine and N-acetylcysteine amide from contact lenses. Atabek Yigit, E., Ercal, N.[2013]

Chitosan-N-acetylcysteine (C-NAC) eye drops significantly increased tear film thickness (TFT) in patients with dry eye syndrome, showing a notable improvement from 3.9 μm to 4.8 μm just 10 minutes after a single dose, and this effect lasted for 24 hours.

Both single and twice-daily applications of C-NAC over 5 days improved symptoms of dry eye, with over 60% of patients experiencing reduced corneal damage, indicating that C-NAC could be an effective treatment option for managing dry eye syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Controlled, Randomized Double-Blind Study to Evaluate the Safety and Efficacy of Chitosan-N-Acetylcysteine for the Treatment of Dry Eye Syndrome. Schmidl, D., Werkmeister, R., Kaya, S., et al.[2018]

N-acetylcysteine (NAC) effectively increases plasma cysteine and glutathione levels, particularly at a dose of 70 mg/kg, which also correlates with improved handgrip exercise performance.

Higher doses of NAC (140 mg/kg) can lead to significant gastrointestinal adverse reactions, suggesting that lower doses may be safer and still effective for enhancing thiol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine in handgrip exercise: plasma thiols and adverse reactions. Ferreira, LF., Campbell, KS., Reid, MB.[2021]

Topical application of 10% N-acetylcysteine (NAC) in male Sprague-Dawley rats led to significant decreases in tear secretion and conjunctival goblet cell numbers, indicating potential ocular surface damage.

The study found that NAC treatment resulted in increased MUC16 concentration in the tear film and ocular surface, suggesting that NAC disrupts the mucin layer, which could be useful for modeling dry eye disease in research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Topical Mucolytic Agents on the Tears and Ocular Surface: A Plausible Animal Model of Mucin-Deficient Dry Eye. Li, X., Kang, B., Woo, IH., et al.[2019]

N-acetylcysteine (NAC) significantly improves the survival of corneal endothelial cells under oxidative and endoplasmic reticulum stress, as shown by increased cell viability in cultured cells pre-treated with NAC.

In a mouse model of early-onset Fuchs endothelial corneal dystrophy, systemic NAC treatment led to higher corneal endothelial cell density and lower cell stress markers, suggesting it could be a promising treatment for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-Acetylcysteine increases corneal endothelial cell survival in a mouse model of Fuchs endothelial corneal dystrophy. Kim, EC., Meng, H., Jun, AS.[2022]

Topical N-acetylcysteine (NAC) significantly reduced protein deposition on contact lenses by 20%, which is important for maintaining lens clarity and comfort for patients with specific ocular conditions.

The treatment with NAC also led to improvements in visual acuity and reduced ocular surface symptoms over two months, indicating its potential as an effective therapy for contact lens wearers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Effect of N-Acetylcysteine on Protein Deposition on Contact Lenses in Patients with the Boston Keratoprosthesis Type I. Kruh, JN., Kruh-Garcia, NA., Foster, CS.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04440280

Targeting Reactive Oxygen Species Production as a Novel ... This protocol will investigate whether topical application of N-acetyl cysteine (NAC) eye drops decreases oxidative stress and confers cytoprotection in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4174697/

N-Acetylcysteine Increases Corneal Endothelial Cell Survival ... Systemic NAC ingestion increases corneal endothelial cell survival which is associated with increased antioxidant and decreased ER stress markers.

3. withpower.com withpower.com/trial/phase-3-corneal-dystrophies-hereditary-10-2020-acec1

NAC Eye Drops for Fuchs' Dystrophy This trial tests if NAC eye drops can protect eye cells by reducing harmful oxidative stress in patients with advanced FECD and cataracts.

4. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT04440280/

Trial | NCT04440280 This protocol will investigate whether topical application of N-acetyl cysteine (NAC) eye drops decreases oxidative stress and confers cytoprotection in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11034696/

Therapeutic future of Fuchs endothelial corneal dystrophy In this review, we aim to summarize the status of FECD treatment, with a particular emphasis on new clinical trials and related research on nonsurgical ...

6. ctv.veeva.com ctv.veeva.com/study/targeting-reactive-oxygen-species-production-as-a-novel-therapeutic-in-fuchs-endothelial-corneal-dy

Targeting Reactive Oxygen Species Production as a Novel ... Subjects in this group will be treated with eye drops containing a 10% solution of N-acetyl cysteine. Topical NAC is a well-tolerated medication that has ...