Evaluation of Sirolimus in the Treatment of Diabetic Macular Edema

西罗莫司治疗糖尿病黄斑水肿的评价

• 批准号: 8177722
• 负责人: Frederick Ferris
• 金额: $ 0.94万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8177722
• 关键词: Adverse event; Affect; Area; Blindness; Cells; Clinical; Cyst; Development; Diabetes Mellitus; Diabetic Retinopathy; Evaluation; Extravasation; Eye; Fluorescein Angiography; Growth Factor; Individual; Infection; Inflammatory; Injection of therapeutic agent; Letters; Liquid substance; Low-Level Laser Therapy; Measures; Microaneurysm; Optical Coherence Tomography; Outcome; Participant; Patients; Pharmaceutical Preparations; Pilot Projects; Play; Process; Production; Proteins; Retina; Retinal; Role; Safety; Severities; Signal Transduction; Sirolimus; Testing; Thick; Toxic effect; Treatment Failure; United States; Vision; Visit; Visual Acuity; diabetic; follow-up; human FRAP1 protein; macula; macular edema; meetings; open label; primary outcome; secondary outcome; success

This study will test whether sirolimus can help patients with diabetic macular edema. The macula, the area of the retina that is responsible for fine vision, can become edematous due to diabetes and result in visual loss. Sirolimus inhibits a protein in the body called mTOR, which plays a critical role in regulating how cells divide and grow. Sirolimus is also believed to affect the inflammatory process. For both these reasons, the drug may be helpful in treating diabetic macular edema. This study is an open label pilot study of five participants with diabetic macular edema. After receiving a 20 L (440 g) subconjunctival injection in the study eye at baseline and Month 2, the participants will be re-evaluated every two months for at least one year for possible additional injections. During follow-up, participants will not undergo re-injection if they show significant clinical improvement or treatment success, defined as no intraretinal fluid or cysts present on optical coherence tomography (OCT) OR 100% reduction in excess retinal thickness over 260 microns on OCT OR no leakage on fluorescein angiography (FA). Beginning at Month 4, participants will be assessed for treatment failure, defined as loss of 15 or more letters of vision compared to baseline at two consecutive visits OR a 50% or greater increase in total retinal thickness as measured by OCT at two consecutive visits. Individual participants deemed treatment failures will continue receiving sirolimus injections, but will be allowed to receive focal laser therapy for any amenable leaking microaneurysms at Month 4. Beginning at Month 6, focal laser therapy will be permitted for both treatment failures and participants who do not meet the criteria of a treatment success. Participants will have the option of continuing treatment until a common termination date of one year. The primary outcome is the change in visual acuity in the study eye at six months compared to baseline. Secondary outcomes include changes in visual acuity in the study eye at one year as compared with baseline, changes in retinal thickness as measured by OCT and changes in fluid leakage in the macula as demonstrated by FA at six months, one year and throughout the study period in the study and fellow eyes. Safety outcomes include number and severity of systemic and ocular toxicities, adverse events and infections, and the number of participants withdrawn from study therapy.

这项研究将测试西罗莫司是否可以帮助糖尿病黄斑水肿患者。黄斑是视网膜上负责精细视力的区域，可由于糖尿病而变得水肿并导致视力丧失。西罗莫司抑制体内一种名为mTOR的蛋白质，该蛋白质在调节细胞如何分裂和生长方面起着关键作用。西罗莫司也被认为影响炎症过程。由于这两个原因，该药物可能有助于治疗糖尿病黄斑水肿。 这项研究是一项开放标签的试点研究，5名参与者与糖尿病黄斑水肿。 在基线和第2个月研究眼接受20 L（440 g）结膜下注射后，将每两个月对受试者进行一次重新评价，持续至少一年，以确定是否可能进行额外注射。 在随访期间，如果受试者表现出显著的临床改善或治疗成功，则不接受再次注射，定义为光学相干断层扫描（OCT）上不存在视网膜内液体或囊肿，或OCT上超过260微米的多余视网膜厚度减少100%，或荧光素血管造影（FA）上无渗漏。 从第4个月开始，将评估受试者的治疗失败，定义为在连续两次访视时与基线相比视力损失15个或更多字母，或在连续两次访视时通过OCT测量的总视网膜厚度增加50%或更多。 被视为治疗失败的个体受试者将继续接受西罗莫司注射，但允许在第4个月时接受局部激光治疗任何适合的微动脉瘤渗漏。从第6个月开始，将允许治疗失败和不符合治疗成功标准的受试者接受局部激光治疗。受试者可以选择继续治疗，直到一年的共同终止日期。 主要结果是与基线相比，研究眼在6个月时的视力变化。 次要结局包括与基线相比，研究眼在1年时的视力变化，通过OCT测量的视网膜厚度变化以及通过FA在6个月、1年和整个研究期间在研究眼和对侧眼中证明的黄斑液体渗漏变化。 安全性结果包括全身和眼部毒性、不良事件和感染的数量和严重程度，以及退出研究治疗的参与者数量。