Targeting Reactive Oxygen Species Production as a Novel Therapeutic in Fuch's Endothelial Corneal Dystrophy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Level of H2O2 in the aqueous humor
研究概览
简要总结
This protocol will investigate whether topical application of N-acetyl cysteine (NAC) eye drops decreases oxidative stress and confers cytoprotection in patients with FECD.
详细描述
Fuchs Endothelial Corneal Dystrophy (FECD) is the most common corneal endothelial disorder and has been estimated to affect approximately 4% of the US population over the age of 40. Corneal transplantation is currently the primary treatment modality available to treat FECD, and there are no medical therapies that treat the disease or stall its progression. Therefore, there is an unmet need to identify pharmacotherapeutic interventions that would prevent the endothelial cell loss in early through late stages of FECD, as well as after corneal transplantation, aiding in the survival of the corneal grafts.
The investigators know that cell loss in FECD is caused by increased oxidative stress in the CEC and aqueous humor of FECD. The investigators have in vitro and in vivo data showing that the processes involved in the development of FECD can be arrested with administration of N-acetyl cysteine (NAC). Currently topical solutions of NAC are already used in ophthalmology for application in keratoconjunctivitis sicca (using 20% weight/volume solution or 10%), meibomian gland dysfunction (using 5%) and Sjögren's dry eye syndrome (also using 5%).
This is a single center, double-blind, placebo-controlled, randomized trial. Adult participants with advanced FECD and cataracts who qualify for the standard treatment (combined Descemet Membrane Endothelial Keratoplasty (DMEK) and cataract surgery) will be enrolled at Massachusetts Eye and Ear.
After meeting eligibility criteria and completing informed consent, 30 eyes from up to 30 participants with advanced FECD and cataracts with indication for combined DMEK and cataract surgery will be initially enrolled. (NOTE: Some participants may be enrolled twice if they elect to have both eyes treated within the study.) Eyes will be randomized 1:1 to NAC 10% and the placebo, Visine Tears Dry Eye Relief artificial tears ophthalmic solution. Each participant will self-administer 1 drop of study drug four times a day in the planned operative eye for 28 days prior to planned surgery.
After interim analysis of the study with 30 eyes, if a significant difference in the primary endpoint between NAC 10% and placebo is not found, an additional 15 eyes from up to 15 participants will be enrolled and assigned to 20% NAC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This is a double-blind trial, where neither the study participant nor the investigators will know to which treatment group the study participant has been assigned.
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥21 years of age at time of surgical evaluation.
- •Diagnosis of advanced FECD and visually significant cataract
- •Indication for DMEK (Descemet Membrane Endothelial Keratoplasty) with concurrent cataract surgery
- •Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
- •Willingness and ability to adhere to medication regimen
排除标准
- •Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- •History of prior intraocular surgery in study eye including cataract, glaucoma and/or retina surgery
- •History of other corneal diseases, such as severe dry eye, corneal scars, pseudophakic bullous keratopathy, corneal degenerations, corneal infections
- •Use of ocular prescription medications except for lubricants, hyperosmotic agents, or ocular hypotensive agents
- •History of ocular surface infection within the past 30 days
- •Use of systemic, inhalational, or topical N-Acetylcysteine within the past 30 days
- •History of intolerance to topical N-Acetylcysteine
- •Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
研究组 & 干预措施
NAC 10% group
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.
干预措施: N-acetyl cysteine (NAC) 10% solution (Drug)
NAC 20% group
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.
干预措施: N-acetyl cysteine (NAC) 20% solution (Drug)
Placebo group
Subjects in this group will be treated with a placebo (Visine Tears Dry Eye Relief artificial tears ophthalmic solution.)
干预措施: Visine Dry Eye Relief eye drops (Drug)
结局指标
主要结局
Level of H2O2 in the aqueous humor
时间窗: DMEK Surgery occurs 28 to 42 days after participant enrollment
The primary endpoint is the level of H2O2 in the aqueous humor obtained at time of DMEK surgery.
次要结局
- Assessment of safety of NAC eye drops in patients with FECD by documenting the number and severity of adverse events.(Ongoing safety assessment will occur starting on the first day when subjects receive the study drug, through the pre-operative visit, surgery and post-surgical follow-up visits, a period of approximately 6-7 weeks.)
- Assessment of tolerability of N-acetyl cysteine drops in patients with FECD by documenting participants' reports of irritation, burning, itchiness or redness in their eyes while taking the study drug(Tolerability will be assessed after participants have taken study drug for 28 days or earlier, if the participants report difficulties tolerating the drug.)
- Changes in corneal tomography after NAC administration(Assessed when subject starts study drug and again, 21 to 28 days later.)
- Change in patient-reported visual disability after NAC administration(Assessed when subject starts study drug and again, 21 to 28 days later.)
- Change in central corneal thickness after NAC administration(Assessed when subject starts study drug and again, 21 to 28 days later.)
- Change in corneal endothelial cell counts after NAC administration(Assessed when subject starts study drug and again, 21 to 28 days later.)
研究者
Ula Jurkunas
Associate Professor, Harvard Medical School
Massachusetts Eye and Ear Infirmary