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: 10615239
• 负责人: PAUL STEVEN BERNSTEIN
• 金额: $ 19.24万
• 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 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615239
• 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; Learning; Life; Life Style; Life Style Modification; Light; Lutein; Marketing; 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 Controlled Clinical Trials; Recommendation; Reproducibility; 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; randomized, clinical trials; 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.

项目摘要/摘要 在过去的二十年中，我们了解到CFH，ARMS2/HTRA1和其他遗传基因座的变体是 与年龄相关的黄斑变性（AMD）的主要危险因素以及补充营养 AREDS2抗氧化剂维生素，矿物质和类胡萝卜素可能会减慢这种盲目疾病的进展。 尽管美国学院眼科（AAO）提出了针对常规基因检测的建议 AMD风险，许多公众表达了进行此类测试和直接面向消费者的兴趣 实验室已经在商业上销售它们。 AAO的专家小组没有断言这些测试没有 准确地反映了AMD视觉丧失的最终风险，而是没有证据表明 AMD风险对行为有任何可量化的影响，可以减轻其高级AMD的发病率 年。一项前瞻性研究表明，对AMD风险的了解可能会降低AMD数十年的发生率 后来将解决这一争议，并与AAO专家的研究建议一致 面板，但由于大量受试者和所需的时间延长，目前不可行。反而， 我们提出了一项较短的2阶段随机临床试验，以研究是否可量化健康行为的生物标志物 （皮肤和眼类胡萝卜素水平）根据了解AMD风险的知识来改善。我们假设这一点 被告知最终AMD风险的个人更有可能持续改变 与较晚的AMD发生率降低相关的行为，例如戒烟，体重减轻， 相对于延期测试的受试者或谁 被告知风险低。然后，这些生活方式的改变将导致黄体素，玉米黄质和 通过共振拉曼光谱（RRS）和反射率在皮肤中测得的其他类胡萝卜素 光谱（RS）和通过自动荧光成像（AFI）和荧光寿命成像眼镜检查 （flio）眼睛。我们将对立即和延期的随机，对照临床试验进行 披露AMD风险以3：1的比率在80岁至64岁的80个正常人中披露。 类胡萝卜素状态将由皮肤RR和RS以及眼AFI和FLIO客观地评估。我们期望 受试者告知AMD的高风险将更有可能启动和维持积极的生活方式改变 这将在一年的研究访问中大大提高他们的皮肤和眼类胡萝卜素的得分。我们也会 确定使用AMD遗传风险与基线眼和全身类胡萝卜素状态之间的相关性 当前和较新的成像方法。