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.

摘要 慢性盆腔疼痛（CPP）对20%的女性的社会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），影响美国6.5%的女性，是其中一种。 最衰弱的CPP条件。骨盆底活动过度（PFOA）在CPP患者中普遍存在， 高达85%的IC/BPS女性存在。保守治疗策略采用物理治疗 包括手动软组织动员、扩张和肌肉再训练的干预。当保守 如果治疗失败，可能需要注射治疗。具体地，肉毒杆菌神经毒素（BoNT，或 onabotulinumtoxinA）在管理PFOA方面受到越来越多的关注。BoNT阻断乙酰胆碱释放， 从而抑制神经肌肉接头（NMJ）处的神经肌肉传递。通过抑制神经肌肉 在痉挛的肌肉中，瞬时肌肉松弛开始，并且疼痛减轻。尽管 虽然BoNT的效力和安全性不高，但它可能引起剂量依赖性的不良反应，而且价格昂贵。研究表明 将注射距离增加1 cm，使BoNT的疗效降低46%。一个 针对NMJ的精确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，NMJ靶向的精确BoNT注射技术还不可用。为了弥补这一差距， CPP管理，我们1）成功开发了一种新型的阴道高密度表面肌电图 （HD-sEMG）技术，以可靠和定量地评估PFOA，并准确地绘制NMJ分布， 过度活跃的骨盆底肌肉（PFMs），和2）成功地证明了显着改善（66%）， 有与没有HD-sEMG指导的BoNT注射治疗结局。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的新技术 注射，使用阴道HD-sEMG指导，用于管理CPP和PFOA。 这个FastTrack SBIR项目旨在开发一种可商业化的，个性化的，精确的BoNT注射医疗器械。 设备，即，PelviMap，利用阴道HD-sEMG技术，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 性能，并将PFOA严重程度评估和NMJ映射算法开发成临床医生友好的 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 将评估开发的个性化，精确的BoNT注射医疗设备（PelviMap）的有效性， 与贝勒大学合作，对46名IC/BPS女性和15名健康对照进行了临床试验研究。 药该提案的可交付成果是首次开发一种上市的NMJ靶向精密度 BoNT注入系统，以优化CPP管理中的BoNT处理效率。成功 商业化可以帮助多达2600万患有CPP并需要更有效治疗的妇女。