A randomized, 双盲, single-center, phase 2 efficacy, and safety study of allogeneic HB-adMSCs for the treatment of patients with Chronic Post-COVID-19 Syndrome
概括
This is an FDA clinical study to evaluate the safety and efficacy of multiple intravenous administrations of allogenic HB-adMSCs for the treatment of Chronic Post-COVID-19 Syndrome. This study was opened to further understand and provide a possible treatment for this rapidly proliferating and often debilitating condition. Stem cells have become a promising tool for the treatment of autoimmune diseases by promoting tissue repair and protection from immune attack associated damage. The mechanism of action for mesenchymal stem cells have been found to include tissue repair, suppression of activation of T and B lymphocytes, release of anti-inflammatory, release of anti-apoptotic molecules, and changes to the differentiation, maturation, and function of dendritic cells, all of which may aid in correcting immune system imbalance and healing of damaged tissues caused by COVID-19 infection and Post COVID-19 Syndrome. 此外, Hope Biosciences Stem Cell Research Foundation has investigated the autologous HB-adMSC product, cells from the participants themselves, for the treatment of Chronic Post-COVID-19 syndrome in an Intermediate Expanded Access Study. In this study, it was shown that HB-adMSCs are safe and there is a potential of HB-adMSCs improving quality of life for patients. We hope to expand on these findings here by investigating the safety and treatment capability of allogenic or donated HB-adMSCs in Chronic Post-COVID-19 Syndrome.
描述
At every infusion, the participant randomized to treatment will receive one allogenic HB-adMSC infusion of 200 million (2 x 10^8) cells through IV over 1 hour (250ml/hr) by a registered nurse. 此外, procedures to monitor safety and improvement will be conducted including pre-infusion verification of informed consent, cell product quality, medical history updates, current medication updates, adverse event updates, vital signs (Heart Rate, 血压, Resp., Temp., SpO2), and a physical exam by a designated physician. During the infusion, vital signs will continue to be monitored and the participant will be observed for a minimum of one hour after the infusion. Fatigue Scale, Visual Analog Scale of Symptoms (增值服务), and Short Form 36 Item Health Survey (SF-36) will be completed by the participant at each visit. At Screening, Infusion 1, and End of Study blood tests will be performed to monitor important inflammatory and safety markers (CBC, Platelets, CMP, PT, PTT, TNFa, IL6, and CRP). Two phone calls for follow up will occur at 4 和 8 weeks after the last infusion. The final visit, End of Study, will include the same procedures with the exception of the infusion and monitoring procedures. A written summary of the results of the treatment, including adverse events will be submitted to the FDA after completion of the last follow-up visit.
Outcome Measure
Changes in Visual Analog Scale of Symptoms, Changes in Fatigue Scale, Changes in Quality of life as seen in the SF-36 assessments, and incidents of adverse events.
Outcome Expectation
We hypothesize that the anti-inflammatory properties of mesenchymal stem cells may offer advantages to patients who are participating in this clinical study.
健康)状况 / Disease
Post-COVID-19 Syndrome (“Long Haul” COVID)
干细胞疗法
iPSC干细胞治疗诊所,东京,日本
WhatsApp: +447778936902 , +33745637397, +34670491885 年龄相关性黄斑变性:RPE细胞 在我们的眼睛中,存在着一种视网膜色素上皮细胞,而在年龄相关性黄斑变性(Age-related macular degeneration,AMD)中,视网膜色素上皮细胞将逐渐丧失功能,并导致黄斑中的光感受器死亡,影响视力甚至最终形成失明。如果早期发现疾病,可以通过抗血管内皮生长因子(anti-VEGF)药物治疗。 日本理化所Masayo Takahashi(也就是高桥政黛)研究组正在研究移植湿性AMD患者iPSC分化的视网膜色素上皮(iPS-RPE)细胞薄片的可行性。采集两例AMD晚期患者的皮肤成纤维细胞,制备成iPS-RPE细胞。在这两例患者中,其中1例患者接受了自体iPS-RPE细胞薄片移植手术。术后1年,移植的RPE细胞薄片证实移植成功,视力得到维持。 随后的临床研究,同样是这个研究团队,将从 HLA-homo iPS 细胞库中制备的RPE细胞移植到与HLA匹配的湿性AMD患者中。局部使用类固醇,没有使用免疫抑制剂。在全部5例接受移植的病例中,经过1年的观察期,证实了移植细胞的存活,并且没有异常生长。在临床试验中,观察到的不良事件包括轻度炎症、疑似轻度排斥反应、视网膜水肿、角膜上皮脱离和无菌性眼内炎。中期结果表明,经过1年的随访,HLA匹配的异体iPS-RPE细胞移植是安全的,并且稳定存活。 -02- 角膜缘干细胞缺乏症:角膜片角膜之所以维持透明,它表面的上皮细胞功不可没。我们人类的角膜上皮细胞不断生长,不断更新,而维持这种更新的源泉就是角膜缘干细胞。当角膜缘干细胞缺乏时(即角膜缘干细胞缺乏症,角膜缘干细胞缺乏,LSCD),会导致角膜上皮持续性缺损,角膜血管化、角膜溃疡感染、不透明,严重者造成角膜穿孔、甚至危及整个眼球,导致失明。供体角膜移植已被用于治疗可能导致失明的严重角膜上皮疾病,但也存在排斥反应和供体短缺的问题。 日本大阪大学的眼科医师 Koji Nishida(西田幸二)团队利用iPSC来源的角膜细胞组织层来修复损伤的角膜。研究小组开发了一种二维培养系统“SEAM方法”,通过促进iPS细胞自分化来组织重建所有的眼样结构。这个细胞薄片构成眼睛的主要细胞群(包含角膜上皮、视网膜和晶状体上皮)出现在组织的特定区域。研究小组从二维组织结构中分离出了角膜上皮祖细胞,并成功地产生了功能性的角膜上皮组织。 iPSC细胞疗法在日本的临床研究 iPSC治疗角膜缘缺乏症示意图 研究小组通过将人类iPSC制备的角膜上皮组织移植到动物模型中,证明了治疗效果。在2019年7月至2020年12月,这个研究小组把用iPSC制作的厚度0.05毫米薄膜状角膜组织,移植给几乎丧失视力的“角膜缘干细胞缺乏症”的4名患者的全球首例临床研究已完成。 此后经过1年的随访观察,未发生排异反应和癌变等问题,确认了安全性。全部患者症状均有改善,其中3人的矫正视力提高,有患者从0.15升至0.7。 -03- 帕金森病:多巴胺神经祖细胞大多数哺乳动物,大脑在胚胎时期就已经完成大部分,只有一小部分神经在出生后持续发展。神经损伤引起的疾病将导致永久性的残疾,如何利用iPSC来修复神经系统是目前干细胞疗法的热门研究。 人们发现利用iPSC分化的多巴胺能神经元可以治疗帕金森病。帕金森病是大脑黑质区(subatantia nigra)分泌多巴胺的神经细胞退化造成的一种疾病。帕金森病仅次于阿尔茨海默病,是第二常见的神经退行性疾病。在美国,男性的终生风险为2%,女性为1.3%。 iPSC细胞疗法在日本的临床研究iPSC治疗帕金森示意图日本京都大学iPS细胞研究所JunTakahashi(高桥淳,也就是高桥政黛的丈夫)研究小组于2018年8月开展使用iPSC来源的多巴胺神经祖细胞治疗帕金森病的临床试验。临床试验移植的细胞来自HLA-homo iPS 细胞库。种子细胞iPSC经过诱导分化,并通过流式细胞仪分选纯化出corin阳性的细胞(corin是多巴胺神经祖细胞的细胞表面标记物)。研究小组将与HLA匹配后的异体iPSC诱导分化为多巴胺神经祖细胞,配合低量免疫抑制剂,通过定位脑手术将大约500万个分化的细胞移植到患者大脑纹状体左右两侧皮质部分。 在临床试验之前,先证实了移植的人类iPSC来源的多巴胺神经祖细胞在帕金森病的食蟹猴模型中的有效性和安全性。经过两年的跟踪,没有观察到猴子肿瘤的形成,也没有发现任何恶性转化的证据,确认了安全性。结果显示:移植的猴子运动活动增加,帕金森病症状有所改善。PET分析显示,移植的细胞在大脑中合成了多巴胺。 -04- 脊髓损伤:神经祖细胞脊髓损伤(Spinal 阅读更多…