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

评估。

• 批准号: 9155610
• 负责人: Catherine Cukras
• 金额: $ 29.38万
• 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/9155610
• 关键词: Adverse event; Affect; Age-Years; Anti-Inflammatory Agents; Anti-inflammatory; Blindness; Chronic; Clinical Research; Dose; Effectiveness; Exhibits; Extravasation; Eye; Fluorescein Angiography; Generations; Histologic; Human; Inflammation; Inflammatory; Injection of therapeutic agent; Injury; Letters; Liquid substance; Longevity; Masks; Measures; Mediation; Microglia; Minocycline; Natural History; Neurons; Oral; Outcome; Participant; Pharmaceutical Preparations; Placebos; Process; Property; Randomized; Research Design; Retina; Retinal; Retinal Vein Occlusion; Safety; Severities; Site; Source; Testing; Tetracyclines; Thick; Time; Toxic effect; Vascular Endothelial Growth Factors; Visit; Visual Acuity; Withdrawal; bevacizumab; cellular targeting; central retinal vein occlusion; improved; inhibitor/antagonist; macula; macular edema; primary outcome; response; secondary outcome; vein occlusion

In these pilot, double-masked, randomized, single-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.

在这些试点、双盲、随机、单中心研究中，参与者将在前三个月每月接受贝伐单抗注射，然后接受 PRN 给药。此外，参与者将每天两次口服 100 毫克米诺环素或安慰剂，以维持治疗。 24个月。在每月一次的访问期间，参与者将测量视力并接受 OCT 测试以测量视网膜厚度。在第 3 个月及之后的访视中，将评估参与者的改善和恶化情况，并将有资格获得额外的贝伐单抗治疗和/或研究产品，具体取决于他们满足的标准。此外，在第 12 个月，还将评估参与者是否有任何改善。 主要结果是 12 个月时研究眼中米诺环素组和安慰剂组之间与基线相比的最佳矫正视力 (BCVA) 平均变化（以 ETDRS 字母测量）的差异。次要结局包括米诺环素组和安慰剂组在 12 至 24 个月与基线之间玻璃体内注射贝伐珠单抗次数的差异，与基线相比在 3、6、12、18 和 24 个月时通过微视野检查测量的平均黄斑敏感性变化，与基线相比 24 个月时 BCVA 的平均变化，在 6、12、18 和 12 个月时通过 OCT 测量的视网膜厚度变化。 24个月相比 基线、与基线相比在 12 和 24 个月时改善 1 logOCT 等级的参与者数量，以及与基线相比在 12 和 24 个月时通过荧光素血管造影证实的黄斑液体渗漏的变化。安全性结果包括参与者退出的数量、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 研究的设计类似，但属于独立的临床研究，因为它们都有自己的自然史过程。 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。