MAMBO: Measuring Ambulation, Motor, and Behavioral Outcomes with post-stroke Fluoxetine in Tanzania

摘要 撒哈拉以南非洲拥有10亿多人口，正在经历一场中风流行病， 与高收入环境相比，死亡率反映了临床结果的巨大差异。 有限的药理学研究已经进行，以改善中风后运动的结果在该地区。 由于撒哈拉以南非洲的中风患者通常比西方国家年轻， 个人财富，可获得和负担得起的选择，不依赖于医疗专家的可用性， 昂贵的治疗将是最有效的。氟西汀是一种选择性5-羟色胺再摄取抑制剂（SSRI）， 在中风后恢复的多项研究中显示出希望。氟西汀在全世界广泛使用 在世界卫生组织的基本药物清单（EML）上，用于治疗抑郁症。 然而，迄今为止，氟西汀的研究仅在相对较少的患者中进行， 现有的试验结果仍然存在争议。氟西汀在撒哈拉以南非洲的使用未经测试， 然而，氟西汀可能是中风幸存者的一种有临床意义且廉价的选择， 改善运动恢复。本研究有两个主要目的：（1）建立临床干预能力 坦桑尼亚达累斯萨拉姆Muhimbili国家医院的中风康复研究-一个低收入的 国家的主要，公共，学术教学医院-重点是为未来的随机， 安慰剂对照临床试验;和（2）确定如果在急性发作后14天内给予氟西汀20 mg， 在100例新发缺血性卒中患者中，缺血性卒中发作后90天内安全且耐受良好。 为了准备中风恢复的随机临床试验的目标， 对工作人员进行临床试验研究方法培训，包括受试者筛选、招募和入组， 随机化、安慰剂的使用和分发、数据安全性和保密性、设盲、研究随访， 要求参与者退出和研究完成、缺失数据和结果报告。这一切成功都 任务将是至关重要的准备合作坦桑尼亚-美国研究小组的随机，安慰剂， 氟西汀的对照试验成功完成目标1，表明将建立 进行中风临床试验，将是非常有价值的Muhimbili国家医院的中风单位， 为未来的介入性卒中研究做好了广泛的准备。成功完成目标2，确认 氟西汀在该人群中安全且耐受性良好，将为更大规模的III期随机 氟西汀与安慰剂在撒哈拉以南非洲的临床试验。

Abstract Sub-Saharan Africa, home to more than 1 billion people, is experiencing a stroke epidemic with morbidity and mortality rates that reflect large disparities in clinical outcomes when compared to higher income settings. Limited pharmacological research has been performed to improve post-stroke motor outcomes in the region. Since stroke patients in Sub-Saharan Africa are often younger than in Western countries and have very limited personal wealth, accessible and affordable options that do not depend on the availability of medical experts or expensive treatments would be most impactful. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) has shown promise in multiple studies of post-stroke recovery. Fluoxetine is widely available throughout the world on Essential Medicines Lists (EMLs) of the World Health Organization for the indication of depression. However, studies of fluoxetine have been performed in relatively small numbers of patients to date, and existing trial findings remain controversial. The use of fluoxetine in Sub-Saharan Africa is untested and not implemented; yet, fluoxetine may be a clinically meaningful and inexpensive option for stroke survivors to improve their motor recovery. This study has two main aims: (1) To build capacity for clinical interventional research on stroke recovery at the Muhimbili National Hospital in Dar es Salaam, Tanzania - a low-income country's main, public, academic teaching hospital - with a focus on setting the stage for a future randomized, placebo-controlled clinical trial; and (2) To determine if fluoxetine 20mg daily, if given within 14 days of acute ischemic stroke onset, is safe and well-tolerated for 90 days post-stroke in 100 new ischemic stroke patients. In order to prepare for the goal of a randomized clinical trial for stroke recovery, significant investments in the training of staff in clinical trial research methods including participant screening, recruitment and enrollment, randomization, use and distribution of placebo, data safety and confidentiality, blinding, study follow up, participant withdrawal and study completion, missing data, and results reporting are required. Each of these tasks will be essential for readying the collaborative Tanzanian-U.S. study team for a randomized, placebo- controlled trial of fluoxetine. Successful completion of Aim 1, demonstrating that capacity will be built for the conduct of stroke clinical trials, will be highly valuable for the Muhimbili National Hospital's stroke unit to broadly prepare for future, interventional stroke research. Successful completion of Aim 2, confirming that fluoxetine is safe and well-tolerated in this population, will provide impetus for a larger, phase III, randomized clinical trial of fluoxetine versus placebo in Sub-Saharan Africa.