An Novel Medical System for Quantitative Diagnosis and Personalized Precision Botulinum Neurotoxin Injection in Chronic Pelvic Pain Management

用于慢性盆腔疼痛管理的定量诊断和个性化精准肉毒杆菌神经毒素注射的新型医疗系统

• 批准号: 10386341
• 负责人: Nicholas Dias
• 金额: $ 25.2万
• 依托单位: HILLMED INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386341
• 关键词: Abdomen; Acetylcholine; Address; Adverse effects; Affect; Age; Algorithms; American; Atopobium vaginae; Bontoxilysin; Clinical; Clinical Trials; Clinical Trials Design; Collaborations; Computer software; Crossover Design; Data; Devices; Diagnosis; Diagnostic; Dose; Effectiveness; Electrodes; Electromyography; Elements; Etiology; Face; Feedback; Focus Groups; Human; Injection of therapeutic agent; Injections; Interstitial Cystitis; Legal patent; Manometry; Manuals; Maps; Measurement; Medical; Medical Device; Medicine; Muscle; Muscle Spasticity; Muscle relaxation phase; Neuromuscular Junction; Pain; Pain management; Patients; Pelvic Examination; Pelvic Floor Muscle; Pelvic floor structure; Pelvis; Performance; Persistent pain; Phase; Physical therapy; Physicians; Quality of life; Randomized; Research; Resolution; Safety; Severities; Small Business Innovation Research Grant; Software Validation; Surface; System; Techniques; Technology; Testing; Therapeutic Effect; Therapeutic Intervention; Time; Treatment Efficacy; Treatment outcome; Treaty; Universities; Vagina; Woman; base; chronic pelvic pain; college; commercial application; commercialization; cost; density; design; diagnostic platform; digital; effective therapy; improved; interest; nerve supply; neuromuscular transmission; novel; recruit; side effect; social; soft tissue; technological innovation; treatment optimization; treatment strategy; usability

Abstract Chronic pelvic pain (CPP) negatively impacts the social and sexual quality of life in up to 20% of women in the US. Interstitial cystitis/ bladder pain syndrome (IC/BPS), which affects 6.5% of women in the US, is one of the most debilitating CPP conditions. Pelvic floor overactivity (PFOA) is prevalent among patients with CPP and presents in up to 85% of women with IC/BPS. Conservative treatment strategies employ physical therapy interventions that include manual soft tissue mobilization, dilation, and muscle retraining. When conservative therapies fail, injection therapies may be indicated. Specifically, botulinum neurotoxin (BoNT, or onabotulinumtoxinA) has received growing interest in managing PFOA. BoNT blocks acetylcholine release, thereby inhibiting neuromuscular transmission at the neuromuscular junction (NMJ). By inhibiting neuromuscular transmission in spastic muscles, transient muscle relaxation commences, and pain is relieved. Despite its potency and safety, BoNT can cause dose-dependent adverse effects and is expensive. Studies have shown that increasing the injection distance by 1 cm away from the NMJs reduces the efficacy of BoNT by 46%. An NMJ-targeted precision BoNT injection technique will retain therapeutic effects, reduce adverse effects and cost. Unfortunately, an NMJ-targeted precision BoNT injection technique is not yet available. To address this gap in CPP management, we have 1) successfully developed a novel vaginal high-density surface electromyography (HD-sEMG) technique to reliably and quantitatively assess PFOA and accurately map the NMJ distributions of overactive pelvic floor muscles (PFMs), and 2) successfully demonstrated a significant improvement (66%) in BoNT injection treatment outcomes with vs. without HD-sEMG guidance. Inspired by the promising research results, the HillMed and the University of Houston PIs co-invented a novel technique for personalized BoNT injections, guided using vaginal HD-sEMG, for managing CPP and PFOA. This FastTrack SBIR project aims to develop a commercializable, personalized, precision BoNT injection medical device, i.e., the PelviMap, utilizing a vaginal HD-sEMG technology, to optimize the treatment outcomes in CPP management. In Phase I, we will develop the vaginal HD-sEMG probe to further improve its diagnostic performance, and develop PFOA severity assessment and NMJ mapping algorithms into a clinician-friendly automated software package, which will be fully integrated into the proposed PelviMap system. In Phase II, we will assess the efficacy of the developed personalized, precision BoNT injection medical device (PelviMap) in a clinical trial study with 46 women with IC/BPS, and 15 healthy controls in collaboration with Baylor College of Medicine. The deliverable of this proposal is to, for the first time, develop a marketed NMJ-targeted precision BoNT injection system to optimize the BoNT treatment efficiency in CPP management. Successful commercialization can help up to 26 million women who suffer from CPP and require more effective therapy.

抽象的 慢性盆腔疼痛 (CPP) 对高达 20% 的女性的社交和性生活质量产生负面影响 我们。间质性膀胱炎/膀胱疼痛综合征 (IC/BPS) 影响着美国 6.5% 的女性，是最常见的疾病之一。 最令人衰弱的 CPP 状况。盆底过度活动症 (PFOA) 在 CPP 患者中很常见， 高达 85% 的患有 IC/BPS 的女性出现这种情况。保守治疗策略采用物理疗法 干预措施包括手动软组织松动、扩张和肌肉再训练。当保守的时候 治疗失败，可能需要注射治疗。具体来说，肉毒杆菌神经毒素（BoNT，或 onabotulinumtoxinA) 在管理 PFOA 方面越来越受到关注。 BoNT 阻断乙酰胆碱释放， 从而抑制神经肌肉接头（NMJ）的神经肌肉传递。通过抑制神经肌肉 痉挛肌肉中的传导，短暂的肌肉松弛开始，疼痛得到缓解。尽管其 BoNT 的效力和安全性可能会导致剂量依赖性不良反应，而且价格昂贵。研究表明 距离 NMJ 增加 1 cm 的注射距离会使 BoNT 的功效降低 46%。一个 NMJ靶向精准BoNT注射技术将保留治疗效果，减少不良反应和成本。 不幸的是，目前还没有针对 NMJ 的精确 BoNT 注射技术。为了解决这一差距 CPP管理方面，我们1）成功研发出新型阴道高密度表面肌电图 (HD-sEMG) 技术可可靠、定量地评估 PFOA 并准确绘制 NMJ 分布图 过度活跃的盆底肌肉 (PFM)，以及 2) 成功证明了以下方面的显着改善 (66%)： 使用和不使用 HD-sEMG 指导的 BoNT 注射治疗结果。受到有前途的研究的启发 结果，HillMed 和休斯顿大学 PI 共同发明了一种个性化 BoNT 新技术 使用阴道 HD-sEMG 引导注射，用于治疗 CPP 和 PFOA。 FastTrack SBIR 项目旨在开发一种可商业化、个性化、精准的 BoNT 注射医疗产品 设备，即 PelviMap，利用阴道 HD-sEMG 技术来优化 CPP 的治疗结果 管理。在第一阶段，我们将开发阴道HD-sEMG探头，以进一步提高其诊断能力 性能，并将 PFOA 严重性评估和 NMJ 映射算法开发为临床医生友好的 自动化软件包，将完全集成到拟议的 PelviMap 系统中。在第二阶段，我们 将评估所开发的个性化精准 BoNT 注射医疗设备 (PelviMap) 的功效 与贝勒学院合作，对 46 名患有 IC/BPS 的女性和 15 名健康对照者进行了临床试验研究 药品。该提案的成果是首次开发一种上市的 NMJ 靶向精度 BoNT 注射系统可优化 CPP 管理中的 BoNT 治疗效率。成功的 商业化可以帮助多达 2600 万患有 CPP 并需要更有效治疗的女性。