Aqueous Humor Dynamic Components That Determine Intraocular Pressure Variance
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 3
- 主要终点
- Variation in eye pressures between individuals
研究概览
简要总结
Glaucoma is a major cause of blindness. The inability to predict a patient's IOP response to medications is a critical barrier for the clinician to consistently provide highly effective IOP-based treatments. Current trial-and-error approaches to glaucoma management are inefficient and have not addressed this barrier as there are no predictive factors for drug response. Our long-term goal is to improve outcomes by identifying biomarkers and environmental factors that profile a patient at risk for glaucoma by age-of-onset, rate of disease progression, "poor response" to treatment, and large IOP fluctuation. Our purpose of this research project is to address this critical barrier by focusing on physiological factors that predict IOP response to drugs.
详细描述
This proposal responded to PA-18-351 "Human Subjects Mechanistic and Minimal Risk Studies" and qualifies as a clinical trial. The central hypothesis is that variations in IOP response to glaucoma drugs and IOP fluctuation can be predicted by the aqueous humor dynamic (AHD) factors that regulate IOP. This hypothesis will be tested in up to 200 participants with ocular hypertension (OHT) or open-angle glaucoma (OAG). This hypothesis will be tested in two aims: Aim 1, Test the hypothesis that AHD factors predict the IOP drug response; Aim 2, Test the hypothesis that aqueous flow and outflow facility predict IOP fluctuation.
The objective is to determine which AHD factors predict a participant's IOP drug response and IOP fluctuation. The scientific rationale is that AHD parameters (aqueous flow, outflow facility, episcleral venous pressure, and uveoscleral flow) determine drug response and IOP fluctuation.
The primary endpoint is IOP response to glaucoma drugs. Exploratory outcome measures include IOP fluctuation and the AHD measures.
The study population includes participants who have either OHT or OAG. The inclusion and exclusion criteria described in 5.3, Study Population. The goal is to recruit 150-200 participants over 4 years.
All drugs and instruments used in this study have been FDA approved.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any self-declared ethnicity-race
- •Open-angle with one of the following:
- •Untreated OHT ≥ 21mmHg
- •Treated OHT with history of IOP ≥ 21 mmHg on 2 prior clinic visits or IOP ≥ 21 mmHg at screening
- •Mild-to-moderate stage open-angle glaucoma based on history of untreated IOP ≥ 21 mmHg
- •Reliable Humphrey visual field test result within previous 1 year
- •Open on gonioscopy within previous 1 year
- •At least one eye must be phakic
- •Able to cooperate for aqueous humor dynamic procedures
- •Able to participate on site over the multi-visit study period
- •Contact lenses must be removed before topical fluorescein instillation and remain out until study testing the following day is completed.
- •Contact lenses must be removed for the entire duration of the study visits.
- •All study medication must be used without contact lenses in the eyes.
排除标准
- •Women who are pregnant or breastfeeding
- •IOP ≥ 38 in study eye(s) or at discretion of the clinician
- •Refusal to remove contact lenses
- •Advanced visual field loss (MD ≤ -16 dB) or threat to fixation in study eye(s) or at discretion of the clinician
- •Study eye(s) with any sign of Fuchs cornea dystrophy as noted clinically with guttae and corneal edema
- •Narrow angle of ≤ Shaffer grade 2 for 180 degrees, peripheral synechiae, or peripheral iridotomy in either eye
- •History of acute angle closure crisis in either eye
- •History of glaucoma incisional surgery (e.g., trabeculectomy, glaucoma drainage implant, Xen gel stent) in study eye(s)
- •History of minimally invasive glaucoma surgery (MIGS, e.g., angle surgery, Cypass) in study eye(s)
- •History of any cycloablation surgery (e.g., micropulse or diode transcleral or endoscopic cyclophotocoagulation) in study eye(s)
- •Study eye cannot have history of any past SLT or ALT glaucoma laser treatments.
- •Study eye(s) cannot have any history of refractive surgery
- •Study eye(s) cannot have any history of herpetic infection of the cornea
- •Study eye(s) cannot have chronic or recurrent inflammatory eye disease
- •Study eye(s) cannot have ocular trauma within the past 6 months, other than uncomplicated cornea abrasion
- •Study eye(s) cannot have ocular infection in the past 3 months
- •Study eye(s) cannot have clinically significant retinal disease that includes proliferative diabetic retinopathy, vein occlusion, cystoid macular edema, wet age-related macular degeneration
- •History of intraocular or peri-ocular injections in study eye(s) within 3 months
- •History of oral steroid use within 30 days of screening Visit 1
- •Any abnormality preventing reliable fluorophotometry (e.g., corneal scarring or severe dry eye with fluorescein staining)
- •Serious hypersensitivity to any components of study medications or risk from treatment (e.g., sulfa drug allergy, bradycardia, severe asthma, or emphysema)
- •Participants must be on minimum 30-day stable regimen prior to Visit 1 for a systemic medication that may affect IOP (i.e., sympathomimetics, beta-blockers, alpha-adrenergic agonists and blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, etc.). Any change of such medication during the study will result in exclusion.
- •Prohibited meds during study: cannabis products, brimonidine 0.025% (Lumify), bimatoprost 0.03% for eyelash growth (Latisse), topical ocular and peri-ocular steroids, oral steroids
研究组 & 干预措施
Timolol 0.5%
To compare the variation in response to timolol between individuals
干预措施: Timolol 0.5% ophthalmic solution (Drug)
Latanoprost 0.005%
To compare the variation in response to latanoprost between individuals
干预措施: Latanoprost 0.005% Ophthalmic Solution (Drug)
结局指标
主要结局
Variation in eye pressures between individuals
时间窗: measurement after 1 week of treatment
Eye pressure is a steady state quantitative trait that is measured in mm Hg. Eye pressure is determined by the following physiological factors (units of measure): eye fluid or aqueous humor production (microliters/minute), aqueous humor outflow (microliters/minute), outflow resistance (microliters/minute/mm Hg) and venous pressure (mm Hg) of the eye. All of these physiological factors will be determined under baseline condition and under glaucoma drug treatment.
次要结局
- Variation in aqueous flow between individuals(measurement 1 week after treatment)
- Variation in episcleral venous pressure(measurement 1 week after treatment)
研究者
Sayoko Moroi
Professor and Chair
Ohio State University