Planning a phase I study of minor salivary gland derived autologous MSCs for prevention of long-term radiation induced xerostomia

计划对小唾液腺来源的自体 MSC 进行 I 期研究，以预防长期辐射引起的口干症

• 批准号: 10720234
• 负责人: RANDALL J KIMPLE
• 金额: $ 15万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10720234
• 关键词: Academic Medical Centers; Acupuncture Therapy; Acute; Adipose tissue; Affect; Allogenic; Amifostine; Autologous; Autologous Transplantation; Bone Marrow; Cancer Center; Candy; Caring; Cell Therapy; Cells; Characteristics; Chewing Gum; Cholinergic Agonists; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Conduct Clinical Trials; Cryopreservation; Data; Deglutition; Dental caries; Dentition; Development; Dimensions; Disease; Dysgeusia; Ensure; Environment; Esthesia; Fatigue; Functional disorder; Goals; Head and Neck Cancer; Head and neck structure; Hyperbaric Oxygen; Impairment; Infection; Information Systems; Infrastructure; Injections; Institution; Interferon Type II; Lead; Licensing; Lubricants; Manuals; Minor salivary gland structure; Mus; Nutritional status; Outcome; Patients; Pharmaceutical Preparations; Phase; Pilot Projects; Population; Preparation; Prevention; Preventive therapy; Preventive treatment; Primary Neoplasm; Procedures; Production; Public Health; Quality of life; Radiation; Radiation therapy; Recommendation; Recovery; Regenerative capacity; Reporting; Research Design; Research Personnel; Resources; Role; Safety; Saliva; Salivary; Salivary Glands; Site; Sleep; Social Functioning; Stimulant; Structure; System; Taste Perception; Technology; Therapeutic; Time; Tissues; Toxic effect; United States National Institutes of Health; Universities; Water; Wisconsin; Work; Xerostomia; clinical trial protocol; effective therapy; emotional functioning; experience; first-in-human; head and neck cancer patient; improved; innovation; lymph nodes; medical schools; mesenchymal stromal cell; morphogens; nutrition; phase 1 study; phase I trial; preclinical study; prevent; research clinical testing; safety testing; saliva composition; saliva function; side effect; stem cell biology; success; sucking; tool

Project Abstract Dry mouth is a significant side-effect of radiation therapy for head and neck cancer patients. Several factors contribute to dry mouth. Decreased production of saliva is called hyposalivation. Poor quality and function of saliva is called salivary dysfunction. Together, these cause xerostomia, or what a patient experiences as simply dry mouth. Xerostomia can lead to tooth decay, infections, difficulty speaking, impaired swallowing, poor nutrition, and has a significant negative effect on quality of life. Doctors recommend that patients suck on hard candy, chew gum, use saliva substitutes, and/or carry a water bottle with them at all times. None of these are particularly effective. Our long-term goal is to prevent the development of long-term radiation-induced dry mouth to improve the quality of life for patients with head and neck cancer. We seek to achieve this goal by providing convincing evidence that innovative cellular therapies can safely and significantly prevent the development of long-term salivary gland dysfunction. The team of investigators tackling this project is uniquely suited to complete the work. Success would lead directly to the next phase of clinical testing. We have expertise in caring for head and neck cancer patients, developing minor salivary gland derived mesenchymal stromal cells (MSCs) as cellular therapies, and studying salivary function. The overall objective of this application is to plan and prepare for a Phase 1 trial to test the safety and tolerability of IFN-g pre-licensed minor salivary gland derived MSCs for prevention of radiation-induced xerostomia in head and neck cancer patients. To achieve our goals, we propose a milestone-based project in which we will work closely with the NIH and FDA to finalize study design for a Phase 1 safety and tolerability study, complete the clinical trial protocol, and submit regulatory documents in Aim 1. In Aim 2, we will complete all necessary milestones to activate the proposed clinical trial including safety systems, data systems, and site staff and facility preparation to ensure a smooth opening to the planned clinical trial.

项目摘要 口干是头颈癌患者放射治疗的一个显着副作用。几个因素 导致口干。唾液分泌减少称为唾液分泌不足。质量和功能较差 唾液分泌过多称为唾液功能障碍。这些因素共同导致口干症，或者患者的经历 简直口干舌燥。口干症可导致蛀牙、感染、说话困难、吞咽障碍、发育不良 营养，并对生活质量产生显着的负面影响。医生建议患者用力吮吸 糖果、口香糖、使用唾液替代品和/或随身携带水瓶。这些都不是 特别有效。我们的长期目标是防止长期辐射引起的干燥的发展 口，以改善头颈癌患者的生活质量。我们寻求通过以下方式实现这一目标 提供令人信服的证据，证明创新的细胞疗法可以安全、显着地预防 长期唾液腺功能障碍的发展。处理这个项目的研究团队是独一无二的 适合完成工作。成功将直接进入下一阶段的临床测试。我们有 护理头颈癌患者、开发小唾液腺间充质细胞的专业知识 基质细胞（MSC）作为细胞疗法，并研究唾液功能。本次活动的总体目标 申请的目的是计划和准备 1 期试验，以测试 IFN-g 预许可的安全性和耐受性 小唾液腺来源的间充质干细胞预防头颈癌辐射引起的口干症 患者。为了实现我们的目标，我们提出了一个基于里程碑的项目，在该项目中我们将与 NIH 和 FDA 确定一期安全性和耐受性研究的研究设计，完成临床试验 协议，并在目标 1 中提交监管文件。在目标 2 中，我们将完成所有必要的里程碑 启动拟议的临床试验，包括安全系统、数据系统以及现场人员和设施准备 确保计划中的临床试验顺利开展。