Ibudilast Phase II trial in progressive MS

异丁司特治疗进展性多发性硬化症的 II 期试验

• 批准号: 9278276
• 负责人: Robert J. Fox
• 金额: $ 28.49万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9278276
• 关键词: Affect; American; Animals; Asthma; Atrophic; Biological Markers; Brain; Brain Injuries; Cerebrospinal Fluid; Cerebrovascular Disorders; Clinical; Clinical Research; Clinical Trials; Data; Diffusion Magnetic Resonance Imaging; Frequencies; Future; Image; In Vitro; Inflammatory Response; Japan; Lesion; Light; Magnetic Resonance Imaging; Measurement; Measures; Migration Inhibitory Factor; Multiple Sclerosis; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neuroprotective Agents; Optical Coherence Tomography; Outcome; Outcome Measure; Patient Self-Report; Patients; Performance; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Placebo Control; Placebos; Plasma; Property; Pyramidal Tracts; Randomized; Relapse; Research Infrastructure; Safety; Sample Size; Signal Transduction; Standardization; Techniques; Testing; Time; arm; base; brain tissue; cerebral atrophy; clinically relevant; cost; design; disability; dosage; efficacy testing; imaging biomarker; imaging modality; imaging potential; inhibitor/antagonist; multiple sclerosis patient; nervous system disorder; neurofilament; neuroprotection; phase II trial; phase III trial; phenylpyruvate tautomerase; phosphoric diester hydrolase; placebo controlled study; prevent; primary outcome; public health relevance; repaired; treatment response; young adult

DESCRIPTION (provided by applicant): Current therapies for multiple sclerosis (MS) inhibit the inflammatory response, but neither sufficiently inhibits ongoing degeneration within the brain nor provide potential repair to injured brain tissue. Consequently, there are no therapies with demonstrated efficacy in slowing, stopping, or reversing the progressive stage of MS, therefore representing an extreme unmet need in neurologic disease. Complicating matters, there are no biological or imaging markers with demonstrated utility for use in Phase 2 trials to screen putative therapies for progressive MS. This study proposes to both test the activity of a potential neuroprotection therapy - ibudilast - in progressive MS and test several candidate imaging measures for their utility in future studies of neuroprotection in progressive MS. We plan to conduct a 2-year; placebo-controlled trial of ibudilast in progressive MS. Multiple advanced imaging modalities will be used to evaluate the activity of ibudilast. At the conclusion of the tril, we will have a clear understanding of the effect of ibudilast on advanced imaging metrics and its safety and potential clinical benefit in progressive MS. Through additional analyses, we will determine which imaging metric provides the most robust and practical outcome for implementation in future clinical trials in progressive MS. Hopefully, this study will show efficac of ibudilast that leads to the first primary neuroprotective drug. Even if ibudilast is not found beneficial, the study will be crucial to the MS field by comparing imaging metrics to support practical Phase II trials for a group of MS patients for whom there is no treatment option.

描述（由申请人提供）：当前多发性硬化症（MS）的疗法抑制炎症反应，但没有足够的抑制大脑内持续的变性，也没有为受伤的脑组织提供潜在的修复。因此，没有疗法在放慢，停止或逆转MS的渐进阶段方面具有疗效，因此代表了神经系统疾病的极端未满足的需求。使事情变得复杂，没有生物学或成像标记物，可以在第二阶段试验中使用效用，以筛选进行性MS的假定疗法。这项研究提议既测试潜力的活性 神经保护疗法 - ibudilast-在进行性MS中，并测试了几种候选成像指标，以实现其在渐进式MS中神经保护的未来研究中的实用性。我们计划进行2年； ibudilast的安慰剂对照试验进行了进步的MS。多种高级成像方式将用于评估ibudilast的活性。在TRIL结束时，我们将清楚地了解ibudilast对高级成像指标及其安全性和潜在临床益处的影响。通过其他分析，我们将确定哪种成像指标为渐进式MS的将来的临床试验中实施提供了最健壮，最实际的结果。希望这项研究能够表明，ibudilast的效果会导致第一种原发性神经保护药物。即使没有发现ibudilast有益，这项研究对于MS领域至关重要，通过比较成像指标来支持一组没有治疗选择的MS患者的实用II期试验。

项目成果

Scan-rescan repeatability and cross-scanner comparability of DTI metrics in healthy subjects in the SPRINT-MS multicenter trial.

SPRINT-MS 多中心试验中健康受试者 DTI 指标的扫描重复性和跨扫描仪可比性。

• DOI: 10.1016/j.mri.2018.07.011
• 发表时间: 2018
• 期刊: Magnetic resonance imaging
• 影响因子: 2.5
• 作者: Zhou,Xiaopeng;Sakaie,KenE;Debbins,JosefP;Narayanan,Sridar;Fox,RobertJ;Lowe,MarkJ
• 通讯作者: Lowe,MarkJ

Quantitative quality assurance in a multicenter HARDI clinical trial at 3T.

• DOI: 10.1016/j.mri.2016.08.022
• 发表时间: 2017-01
• 期刊: Magnetic resonance imaging
• 影响因子: 2.5
• 作者: Zhou X;Sakaie KE;Debbins JP;Kirsch JE;Tatsuoka C;Fox RJ;Lowe MJ
• 通讯作者: Lowe MJ

Technical Note: Retrospective reduction in systematic differences across scanner changes by accounting for noise floor effects in diffusion tensor imaging.

技术说明：通过考虑扩散张量成像中的本底噪声效应，回顾性地减少扫描仪变化时的系统差异。

• DOI: 10.1002/mp.13088
• 发表时间: 2018
• 期刊: Medical physics
• 影响因子: 3.8
• 作者: Sakaie,Ken;Zhou,Xiaopeng;Lin,Jian;Debbins,Josef;Lowe,Mark;Fox,RobertJ
• 通讯作者: Fox,RobertJ