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

评估。

• 批准号: 8737681
• 负责人: Catherine Cukras
• 金额: $ 15.84万
• 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/8737681
• 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.

在这些试验性、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珠单抗注射，随后接受PRN给药。此外，参与者将口服100 mg米诺环素或安慰剂，每日两次， 24个月在每个月的访视期间，参与者将测量他们的视力，并将接受OCT测试以测量视网膜厚度。在第3个月访视时及之后，将评价受试者的改善和恶化，并根据其符合的标准，有资格接受额外的贝伐珠单抗治疗和/或试验用药物。此外，在第12个月时，还将评估受试者是否无改善。 主要结局是12个月时二甲胺四环素组和安慰剂组研究眼的最佳矫正视力（BCVA）与基线相比的平均变化差异（以ETDRS字母测量）。次要结果包括米诺环素组和安慰剂组之间在12个月和24个月与基线之间玻璃体内贝伐单抗注射次数的差异，与基线相比在3个月、6个月、12个月、18个月和24个月通过微视野计测量的平均黄斑敏感度的变化，与基线相比在24个月BCVA的平均变化，与基线相比在6个月通过OCT测量的视网膜厚度的变化，12、18和24个月时与基线相比，12和24个月时与基线相比改善1 logOCT量表步长的受试者数量，以及12和24个月时与基线相比通过荧光素血管造影术证明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研究的设计相似，但它们是单独的临床研究，因为它们各自有自己的自然病程。 因此，我们希望在比较对研究药物的反应时将它们分开。