Eval. of Minocycline as a Microglia Inhibitor in Tx of CRVO and BRVO

评估。

• 批准号: 10706122
• 负责人: Catherine Cukras
• 金额: $ 8.75万
• 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/10706122
• 关键词: Adverse event; Affect; Age-Years; Anti-Inflammatory Agents; Blindness; Chronic; Clinical Research; Dose; Effectiveness; Exhibits; Extravasation; Eye; Fluorescein Angiography; Generations; Human; Inflammation; Inflammatory; Injections; Injury; Investigation; Length; Letters; Liquid substance; Masks; Measures; Mediation; Microglia; Minocycline; Multicenter Studies; Natural History; Neurons; Oral; Participant; Patient Recruitments; Patients; Persons; Pharmaceutical Preparations; Placebos; Process; Property; Randomized; Retina; Retinal Vein Occlusion; Safety; Severities; Site; Source; Testing; Tetracyclines; Thick; Time; Toxic effect; Treatment Factor; Vascular Endothelial Growth Factors; Visit; Visual Acuity; Withdrawal; bevacizumab; cellular targeting; central retinal vein occlusion; design; histological studies; improved; inhibitor; macula; macular edema; placebo group; primary outcome; response; safety outcomes; secondary outcome; vein occlusion

In these pilot, double-masked, randomized, multi-center studies, participants will receive monthly bevacizumab injections for the first three months, followed by PRN dosing. In addition, participants will take an oral dose of 100 mg of minocycline or placebo twice daily for 24 months. During each monthly visit, participants will have their visual acuity measured and will undergo OCT testing to measure retinal thickness. At the Month 3 visit and thereafter, participants will be evaluated for improvement and worsening and will be eligible for additional bevacizumab treatment and/or investigational product depending on which criteria they fulfill. Additionally, at Month 12, participants will also be evaluated for no improvement. The primary outcome is the difference in mean change in best-corrected visual acuity (BCVA), as measured in ETDRS letters, between the minocycline and placebo groups in the study eye at 12 months compared to baseline. Secondary outcomes include the difference between the minocycline and placebo groups in the number of intravitreal bevacizumab injections between 12 and 24 months and baseline, changes in mean macular sensitivity as measured by microperimetry at 3, 6, 12, 18 and 24 months compared to baseline, the mean change in BCVA at 24 months compared to baseline, changes in retinal thickness as measured by OCT at 6, 12, 18 and 24 months compared to baseline, number of participants improving 1 logOCT scale step at 12 and 24 months compared to baseline, as well as changes in fluid leakage in the macula as demonstrated by fluorescein angiography at 12 and 24 months compared to baseline. Safety outcomes include the number of participant withdrawals, the number and severity of systemic and ocular toxicities and the number of adverse events. BRVO and CRVO studies are designed similarly but are separate clinical studies as they each have their own natural history course. We therefore want to keep them separate as we compare responses to investigative drug. The studies have been expanded to include two sites in the UK. One site in the UK has started recruiting patients and has active study patients, the other site is activating shortly.

在这些试点、双掩蔽、随机、多中心研究中，参与者将在前三个月每月接受贝伐单抗注射，然后是PRN剂量。此外，参与者将口服100毫克的米诺环素或安慰剂，每天两次，用于 24个月。在每个月的访问中，参与者将测量他们的视力，并接受OCT测试来测量视网膜厚度。在第3个月及以后的访问中，参与者将接受改善和恶化的评估，并将有资格接受额外的贝伐单抗治疗和/或研究产品，具体取决于他们符合的标准。此外，在第12个月，参与者也将接受无进步的评估。 主要结果是研究眼在12个月时与基线相比，米诺环素组和安慰剂组之间最佳矫正视力(BCVA)的平均变化(以ETDRS字母测量)的差异。次要结果包括米诺环素组和安慰剂组之间玻璃体内注射贝伐单抗的次数与基线的差异，在3、6、12、18和24个月时通过微视野测量的平均黄斑敏感度与基线相比的变化，24个月时的BCVA与基线的平均变化，6、12、18和24个月的OCT测量的视网膜厚度与基线的变化，12和24个月时参与者的数量与基线相比改善了1logOCT标准步长，以及12和24个月的荧光血管造影术显示的黄斑液体渗漏的变化。安全性结果包括参与者停药的次数、全身和眼部毒性的数量和严重程度以及不良事件的数量。 BRVO和CRVO研究设计相似，但都是独立的临床研究，因为它们都有自己的自然病程。因此，当我们比较对研究药物的反应时，我们希望将它们分开。 这些研究已经扩大到包括英国的两个地点。英国的一个网站已经开始招募患者，并有活跃的研究患者，另一个网站很快就会启动。