NAC Eye Drops for Fuchs' Dystrophy
Recruiting in Palo Alto (17 mi)
Overseen byUla Jurkunas, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts Eye and Ear Infirmary
Must not be taking: N-Acetylcysteine
Disqualifiers: Pregnancy, Prior eye surgery, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial tests if NAC eye drops can protect eye cells by reducing harmful oxidative stress in patients with advanced FECD and cataracts. The study involves patients who are already scheduled for eye surgeries. NAC is expected to help by protecting the corneal cells from damage. NAC has been used topically in the treatment of various eye conditions due to its antioxidant, anti-inflammatory, and mucolytic properties.
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.
What data supports the effectiveness of the drug N-acetyl cysteine (NAC) eye drops for Fuchs' Dystrophy?
Research shows that N-acetyl cysteine (NAC) can help protect corneal cells from stress and improve their survival in a mouse model of Fuchs' Dystrophy, suggesting it might be beneficial for this condition.
12345Is N-acetylcysteine (NAC) generally safe for human use?
N-acetylcysteine (NAC) has been used safely for several decades as a treatment for conditions like acetaminophen poisoning and respiratory diseases, but it can cause some adverse reactions in humans.
12367How is the drug N-acetyl cysteine (NAC) unique for treating Fuchs' Dystrophy?
N-acetyl cysteine (NAC) eye drops are unique for treating Fuchs' Dystrophy because they help protect corneal cells from oxidative stress (damage caused by harmful molecules) and endoplasmic reticulum stress (cellular stress related to protein folding), which are key factors in this condition. This approach is different from other treatments that may not specifically target these stress pathways.
12489Eligibility Criteria
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
+3 more
Exclusion Criteria
I have a history of serious eye conditions affecting the cornea.
I use eye medication, but only for dryness, swelling, or pressure.
Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
+5 more
Trial Timeline
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)
Participant Groups
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.
3Treatment groups
Active Control
Placebo Group
Group I: NAC 20% groupActive Control1 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% groupActive Control1 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 groupPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts Eye and Ear InfirmaryBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts Eye and Ear InfirmaryLead Sponsor
References
N-Acetylcysteine increases corneal endothelial cell survival in a mouse model of Fuchs endothelial corneal dystrophy. [2022]The present study evaluated survival effects of N-acetylcysteine (NAC) on cultured corneal endothelial cells exposed to oxidative and endoplasmic reticulum (ER) stress and in a mouse model of early-onset Fuchs endothelial corneal dystrophy (FECD). Cultured bovine corneal endothelial cell viability against oxidative and ER stress was determined by CellTiter-Glo(®) luminescent reagent. Two-month-old homozygous knock-in Col8a2(L450W/L450W) mutant (L450W) and C57/Bl6 wild-type (WT) animals were divided into two groups of 15 mice. Group I received 7 mg/mL NAC in drinking water and Group II received control water for 7 months. Endothelial cell density and morphology were evaluated with confocal microscopy. Antioxidant gene (iNos) and ER stress/unfolded protein response gene (Grp78 and Chop) mRNA levels and protein expression were measured in corneal endothelium by real time PCR and Western blotting. Cell viability of H2O2 and thapsigargin exposed cells pre-treated with NAC was significantly increased compared to untreated controls (p
N-acetylcysteine in chronic blepharitis. [2019]To investigate the effects of N-acetylcysteine (NAC) in chronic posterior blepharitis.
The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress. [2022]Oxidative stress, which results in the damage of diverse biological molecules, is a ubiquitous cellular process implicated in the etiology of many illnesses. The sulfhydryl-containing tripeptide glutathione (GSH), which is synthesized and maintained at high concentrations in all cells, is one of the mechanisms by which cells protect themselves from oxidative stress. N-acetylcysteine (NAC), a synthetic derivative of the endogenous amino acid L-cysteine and a precursor of GSH, has been used for several decades as a mucolytic and as an antidote to acetaminophen (paracetamol) poisoning. As a mucolytic, NAC breaks the disulfide bonds of heavily cross-linked mucins, thereby reducing mucus viscosity. In vitro, NAC has antifibrotic effects on lung fibroblasts. As an antidote to acetaminophen poisoning, NAC restores the hepatic GSH pool depleted in the drug detoxification process. More recently, improved knowledge of the mechanisms by which NAC acts has expanded its clinical applications. In particular, the discovery that NAC can modulate the homeostasis of glutamate has prompted studies of NAC in neuropsychiatric diseases characterized by impaired glutamate homeostasis. This narrative review provides an overview of the most relevant and recent evidence on the clinical application of NAC, with a focus on respiratory diseases, acetaminophen poisoning, disorders of the central nervous system (chronic neuropathic pain, depression, schizophrenia, bipolar disorder, and addiction), cardiovascular disease, contrast-induced nephropathy, and ophthalmology (retinitis pigmentosa).
Release of N-acetylcysteine and N-acetylcysteine amide from contact lenses. [2013]To investigate the use of contact lenses to release N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) that have frequently used for the treatment of some eye diseases.
Evaluation of the Effect of N-Acetylcysteine on Protein Deposition on Contact Lenses in Patients with the Boston Keratoprosthesis Type I. [2015]To establish the efficacy of topical N-acetylcysteine (NAC) as a treatment to reduce protein deposition on the contact lens surface.
N-acetylcysteine in handgrip exercise: plasma thiols and adverse reactions. [2021]N-acetylcysteine (NAC) is a thiol donor with antioxidant properties that has potential use as an ergogenic aid. However, NAC is associated with adverse reactions that limit its use in humans.
Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients. [2018]N-acetylcysteine (NAC) is a mucolytic agent with anti-oxidant properties. It might have potential positive effects in renal patients and, therefore, its pharmacokinetics and safety in haemodialysis was investigated.
A Controlled, Randomized Double-Blind Study to Evaluate the Safety and Efficacy of Chitosan-N-Acetylcysteine for the Treatment of Dry Eye Syndrome. [2018]This study was designed to evaluate the effect of chitosan-N-acetylcysteine (C-NAC) eye drops on tear film thickness (TFT) in patients with dry eye syndrome (DES).
Effects of Topical Mucolytic Agents on the Tears and Ocular Surface: A Plausible Animal Model of Mucin-Deficient Dry Eye. [2019]A topical mucolytic agent, N-acetylcysteine (NAC), has been used to create an animal model without the intestinal mucus layer. In this study, we investigated the effects of topical NAC on the tears and ocular surface.