A Phase 2 Study of the Value of Pre-symptomatic Genetic Risk Assessment for Age-Related Macular Degeneration

年龄相关性黄斑变性症状前遗传风险评估价值的 2 期研究

• 批准号: 10387057
• 负责人: PAUL STEVEN BERNSTEIN
• 金额: $ 23.03万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10387057
• 关键词: Academy; Age; Age related macular degeneration; American; Antioxidants; Behavior; Biological Markers; Blindness; Body Weight decreased; Carotenoids; Clinical; Clinical Research; Clinical Trials; Deposition; Diet; Disclosure; Disease; Eye; Future; Genetic Risk; Image; Incidence; Individual; Knowledge; Laboratories; Lead; Life; Life Style; Life Style Modification; Light; Lutein; Measures; Methods; Minerals; Multicenter Trials; Ophthalmology; Ophthalmoscopy; Other Genetics; Pattern; Phase; Phase II Clinical Trials; Pilot Projects; Prospective Studies; Public Health; Raman Spectrum Analysis; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Recommendation; Research; Risk; Risk Factors; Signs and Symptoms; Skin; Spectrum Analysis; Testing; Time; Variant; Visit; Vitamins; absorption; combat; design; fluorescence lifetime imaging; genetic risk assessment; genetic risk factor; genetic testing; genomic locus; high risk; imaging modality; improved; interest; macula; member; nutritional supplementation; phase 2 study; presymptomatic testing; response; risk variant; smoking cessation; trial comparing; zeaxanthin

Project Summary/Abstract In the past two decades, we have learned that variants in CFH, ARMS2/HTRA1 and other genetic loci are major risk factors for age-related macular degeneration (AMD) and that nutritional supplementation with AREDS2 antioxidant vitamins, minerals, and carotenoids could slow the progression of this blinding disorder. Despite recommendations by the American Academy Ophthalmology (AAO) against routine genetic testing for AMD risk, many members of the public express an interest in pursuing such testing, and direct-to-consumer laboratories already market them commercially. The AAO's expert panel did not assert that these tests do not accurately reflect eventual risk of visual loss from AMD, but rather that there is no proof that knowledge of AMD risk has any quantifiable impact on behavior that could mitigate the incidence of AMD in their senior years. A prospective study to show that knowledge of AMD risk could decrease incidence of AMD decades later would settle this controversy and would be consistent with research recommendations of the AAO expert panel, but it is not currently feasible due to the large number of subjects and prolonged time required. Instead, we propose a shorter, Phase 2 randomized clinical trial to study if quantifiable biomarkers of healthy behavior (skin and ocular carotenoid levels) improve in response to knowledge of AMD risk. We hypothesize that individuals who are informed of a high risk of eventual AMD will be more likely to make sustained changes in behavior associated with decreased incidence of AMD later in life such as smoking cessation, weight loss, decreased light exposure, and diets rich in carotenoids relative to subjects who have deferred testing or who are informed of low risk. These lifestyle changes will then result in improved levels of lutein, zeaxanthin, and other carotenoids measured in the skin at one year by resonance Raman spectroscopy (RRS) and reflectance spectroscopy (RS) and by autofluorescence imaging (AFI) and fluorescence lifetime imaging ophthalmoscopy (FLIO) in the eye. We will conduct a randomized, controlled clinical trial of immediate versus deferred disclosure of AMD risk in a 3:1 ratio in up to 80 normal individuals age 18 to 64. Systemic and ocular carotenoid status will be assessed objectively by skin RRS and RS and by ocular AFI and FLIO. We expect that subjects informed of high risk of AMD will be more likely to initiate and sustain positive lifestyle changes that will raise their skin and ocular carotenoid scores significantly at their one-year study visit. We will also determine correlations between AMD genetic risk with baseline ocular and systemic carotenoid status using current and newer methods of imaging.

项目概要/摘要 在过去的二十年里，我们了解到CFH、ARMS2/HTRA1等基因位点的变异 年龄相关性黄斑变性（AMD）的主要危险因素以及营养补充剂 AREDS2 抗氧化维生素、矿物质和类胡萝卜素可以减缓这种致盲性疾病的进展。 尽管美国眼科学会 (AAO) 建议不要进行常规基因检测 AMD 风险，许多公众表示有兴趣进行此类测试，并直接面向消费者 实验室已经将它们商业化销售。 AAO 的专家小组并未断言这些测试不会 准确地反映了 AMD 导致视力丧失的最终风险，但没有证据表明了解 AMD 风险对行为有任何可量化的影响，可以减轻老年人 AMD 的发病率 年。一项前瞻性研究表明，了解 AMD 风险可以降低 AMD 的发病率数十年 稍后将解决这一争议，并与 AAO 专家的研究建议一致 小组，但由于受试者数量众多且所需时间较长，目前尚不可行。反而， 我们提出了一项更短的二期随机临床试验来研究健康行为的可量化生物标志物 （皮肤和眼睛的类胡萝卜素水平）随着对 AMD 风险的了解而提高。我们假设 被告知最终患有 AMD 的高风险的个人更有可能做出持续的改变 与晚年 AMD 发病率降低相关的行为，例如戒烟、减肥、 与推迟测试或未接受测试的受试者相比，光照减少以及富含类胡萝卜素的饮食 被告知低风险。这些生活方式的改变将导致叶黄素、玉米黄质和 通过共振拉曼光谱 (RRS) 和反射率在一年内测量皮肤中的其他类胡萝卜素 光谱 (RS) 以及自体荧光成像 (AFI) 和荧光寿命成像检眼镜 （FLIO）在眼睛里。我们将进行一项立即与延迟治疗的随机对照临床试验 以 3:1 的比例披露了多达 80 名年龄在 18 岁至 64 岁之间的正常人的 AMD 风险。 全身和眼部 类胡萝卜素状态将通过皮肤 RRS 和 RS 以及眼部 AFI 和 FLIO 进行客观评估。我们期望 被告知患有 AMD 高风险的受试者将更有可能开始并维持积极的生活方式改变 这将在为期一年的研究访问中显着提高他们的皮肤和眼部类胡萝卜素分数。我们也会 使用基线眼部和全身类胡萝卜素状态确定 AMD 遗传风险之间的相关性 当前和更新的成像方法。