BioSphincter to Treat Fecal Incontinence. Phase 1/2 Clinical Trial. SBIR Phase IIB

生物括约肌治疗大便失禁。

• 批准号: 9770834
• 负责人: KHALIL N BITAR
• 金额: $ 139.36万
• 依托单位: CELLF-BIO, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-23 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9770834
• 关键词: Address; Animals; Anterior; Biocompatible Materials; Biomedical Engineering; Blood Vessels; Cells; Circular layer of muscularis propria of anal canal; Clinical Trials; Constipation; Data; Diarrhea; Disease; Distress; Engineering; Fecal Incontinence; Feces; Guidelines; Health Personnel; Hygiene; Implant; Incontinence; Injections; Liquid substance; Measures; Methods; Muscle function; National Institute of Diabetes and Digestive and Kidney Diseases; Natural regeneration; Operative Surgical Procedures; Patients; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phenotype; Physiological; Population; Prevalence; Procedures; Prospective Studies; Quality of life; Regenerative Medicine; Reporting; Rodent; Sacral nerve; Safety; Severities; Skeletal Muscle; Small Business Innovation Research Grant; Smooth Muscle; Soil; Solid; Sphincter; Striated Muscles; Structure; Therapeutic Effect; United States National Institutes of Health; Woman; aged; implantation; improved; innovation; manufacturing scale-up; men; nerve supply; neuroregulation; novel strategies; novel therapeutics; pressure; psychologic; reconstitution; repaired; restoration; sensory mechanism; social; symptom management

Project Summary/Abstract: Fecal incontinence (FI), the involuntary soiling of various amounts of liquid and solid stool, is often devastating from a social, psychological, and hygiene perspective. Men and women suffer from FI equally with a range of 2 - 6% in people aged 20 - 30 years. The prevalence increases to over 15% in people older than 70 years1. FI may result from an isolated or combined loss of smooth muscle function (IAS), skeletal muscle function (EAS), anorectal sensory mechanisms or neural control. Treatment of FI is initially conservative with attempts to bulk the stool, adjust or stop drugs that cause either diarrhea or constipation, and biofeedback2,3. While these conservative measures may improve the severity of FI, additional therapies are needed for total symptom management. Injection of various biomaterials to augment the internal anal sphincter has also been attempted4, but results have been variable and of limited duration when effective. In the past, surgical attempts with anterior/posterior surgical repair have been tried such as graciloplasty and sacral nerve stimulation5,6, but long-term results have been disappointing6. There is a critical need for new therapies to address FI, particularly for patients who have severe passive incontinence and low IAS pressure. Regenerative medicine methods, wherein a new IAS BioSphincter™ is bioengineered from the patient's own cells and implanted to restore the structure and function of the IAS and treat FI, represents a rational and novel approach to this debilitating disease. Regeneration and implantation of the IAS “BioSphincter™” can restore physiological function of the IAS, improve or resolve FI, and improve quality of life. Following implantation in rodents, the engineered sphincters became vascularized and maintained their phenotype and functionality7,8. Further in our large animal studies, the developed IAS BioSphincter™ were validated to treat the FI and successfully restored anorectal functionality in rabbit9,10 and non-human primates11. The IAS BioSphincter™ was developed in GLP condition further scaled up for manufacturing following GMP guidelines and put together for FDA application. According to NIDDK, NIH, one out of three people report to health care providers owing to fecal incontinence, therefore, regeneration and implantation of the IAS “Biosphincter™” will benefit a large socially distressed segment of population via restoration of physiological function of the IAS, resolve FI, and improving quality of life. The primary objectives of the phase I clinical trial study are to: 1) determine the safety of the implanted bioengineered IAS in patients with severe FI and 2) to analyse the data in order to assess the initial efficacy potentials of the implanted IAS in decreasing the number of episodes of incontinence in patients with severe FI. This new innovative approach will provide the patients with a better quality of life, and reinstate continence, by providing an additive functional intrinsically innervated IAS bioengineered from their own cells.

项目摘要/摘要： 粪便尿失禁（FI）是各种液体和固体粪便的非自愿弄脏，通常是 从社会，心理和卫生的角度造成毁灭性。男人和女人与 20至30岁的人中有2-6％的范围。年龄超过70人的患病率增加到超过15％ 年1。 FI可能是由于平滑肌功能（IAS），骨骼肌肉的孤立或组合丧失所致 功能（EAS），肛门直肠感觉机制或神经控制。 FI的治疗最初是保守的，试图散装凳子，调整或停止引起的药物 腹泻或便秘，生物反馈2,3。尽管这些保守措施可能会改善 FI的严重程度，全部症状管理需要其他疗法。注入各种生物材料 为了增加内部肛门括约肌，也尝试过4，但结果是可变且有限的 持续时间有效。过去，已经尝试了前/后手术修复的手术尝试 例如gracillopplastus和s骨神经刺激5,6，但长期的结果令人失望。6。 新疗法需要解决FI的迫切需要，特别是对于严重的患者 被动尿失禁和低IAS压力。再生医学方法，其中新的IAS Biosphincter™是从患者自己的细胞中生物工程的，并植入以恢复结构和 IAS和治疗FI的功能代表了这种使人衰弱的疾病的理性和新方法。 IAS的再生和植入“ Biosphincter™”可以恢复IAS的生理功能， 改善或解决FI并改善生活质量。在啮齿动物实施后，工程括约肌 成为血管化并保持其表型和功能7,8。在我们的大型动物研究中， 开发的IAS Biosphincter™经过验证以治疗FI并成功恢复了厌食症 Rabbit9,10和非人类Primes11中的功能11。 IAS Biosphincter™是在GLP条件下开发的 根据GMP指南进一步扩展制造，并汇总FDA应用程序。根据 致NIH的NIDD，三分之三的人报告给医疗保健提供者，因此，由于粪便失禁 IAS的再生和植入“ Biosphincter™”将受益于大型社会困扰部分 通过恢复IAS的身体功能，解决FI和改善生活质量的人口。 I期临床试验研究的主要目标是：1）确定植入的安全性 严重FI和2）患者的生物工程IAS分析数据以评估初始效率 植入的IAS的电势减少严重患者的失禁次数 fi。这种新的创新方法将为患者提供更好的生活质量，并恢复持续的生活， 通过提供从其自己的细胞中生物工程的额外的固有神经支配的IAS。