Gyrate Atrophy Ocular and Systemic Study (GYROS)

回旋萎缩眼部和全身研究 (GYROS)

• 批准号: 10573885
• 负责人: Allison Renee Ayala
• 金额: $ 40万
• 依托单位: JAEB CENTER FOR HEALTH RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10573885
• 关键词: Gyrate; Atrophy; Ocular; Systemic; Study

1 Project Summary/Abstract for GYROS 2 Gyrate atrophy is a rare inherited chorioretinal degeneration that is associated with 3 hyperornithinemia caused by autosomal recessive mutations in the ornithine aminotransferase 4 (OAT) gene and leads to severe loss of vision. The current standard of care treatment is a 5 highly burdensome arginine-restricted diet (ARD) fraught with management complications. The 6 principal investigators are currently developing a gene augmentation therapy, a potential 7 treatment strategy that may preserve or improve vision while avoiding or reducing the 8 need for ARD. To facilitate a future interventional clinical trial, there is a need to characterize 9 the natural history of OAT-related ocular and systemic disease progression. The study aims are: 10 1. Natural History – Characterize the natural history of ornithine levels and retinal 11 degeneration (RD) associated with disease-causing OAT variants in the presence of 12 standard dietary treatment regimens over 4 years, using metabolic measures of fasting 13 plasma and blood spot amino acids panels, functional and structural measures of RD, 14 and patient-reported outcome measures. 15 2. Metabolic-Structure-Function Relationships – Explore the relationships between 16 structural and functional RD outcome measures and plasma ornithine levels. 17 3. Identify Rapid Progressors – Explore the relationship of possible risk factors 18 (genotype, phenotype, environmental, standard care dietary regimen) with severity and 19 progression of outcome measures. 20 This natural history study will inform the future interventional clinical trial design as follows: 21  Determine within-patient variability of ornithine levels 22  Develop quantitative measures of progression of the area of preserved retina and 23 establish its reproducibility, sensitivity to change, and relationship with other measures 24  Establish rates of progression of functional RD, structural RD, and patient-reported 25 outcome measures, and determine which measures are most sensitive to change 26  Determine primary time points and duration for a planned future treatment trial 27  Use variability and inter-eye correlation of outcomes for trial sample size calculations 28  Identify candidates for the future trial, including eligibility criteria based on risk factors 29 and cut points for severity of disease most likely to benefit from treatment 30  Establish study procedures and workflows

1个陀螺仪的项目摘要/摘要 2回旋萎缩是一种罕见的遗传性平民变性，与 鸟氨酸氨基转移酶中的常染色体隐性突变引起的3个高义氨酸血症 4（燕麦）基因，导致严重的视力丧失。当前的护理治疗标准是 5高度燃烧的精氨酸限制饮食（ARD）充满了管理并发症。这 6个主要研究人员目前正在开发一种基因增强疗法，潜力 7可以保留或改善视力的治疗策略，同时避免或减少 8需要ARD。为了促进将来的介入临床试验，有必要表征 9与燕麦相关的眼和全身性疾病进展的自然历史。研究目的是： 10 1。自然历史 - 表征鸟氨酸水平的自然历史并保持 在存在的情况下，11与引起疾病的燕麦变体相关的变性（RD） 12个标准饮食治疗方案在4年内，使用代谢措施 13血浆和血点氨基酸面板，RD的功能和结构度量， 14和患者报告的结果指标。 15 2。代谢结构功能关系 - 探索 16结构和功能性RD结果指标和血浆鸟氨酸水平。 17 3.确定快速进步者 - 探索可能的风险因素的关系 18（基因型，表型，环境，标准护理饮食方案）严重程度和 19结果措施的进展。 20这项自然史研究将为未来的介入临床试验设计提供如下： 21确定鸟氨酸水平的患者内变异性 22制定保留视网膜区域进展的定量测量 23建立其可重复性，对变革的敏感性以及与其他措施的关系 24建立功能RD，结构RD和患者报告的进展率 25种结果度量，并确定哪些措施对改变最敏感 26确定计划的未来治疗试验的主要时间点和持续时间 27使用结果的变异性和眼球间相关性进行试验样本量计算 28确定未来审判的候选人，包括基于风险因素的资格标准 29和疾病严重程度的切点，最有可能受益于治疗 30建立学习程序和工作流程