Randomized controlled clinical trial of botulinum toxin for myofascial TMJD pain

描述(由申请人提供)：虽然文献几乎没有证据表明它对于这一适应症是安全或有效的，但A型肉毒毒素(BONT/A)作为持续性肌筋膜颞下颌肌和关节紊乱(TMJD)患者的治疗方案最近受到了极大的关注。如果它被证明是安全和有效的，注射到咀嚼肌肉，它可能被证明对许多对现有治疗方式无效的TMJD患者来说是非常宝贵的。几项研究报告了疗效的模棱两可的证据，但仔细检查表明，这些研究要么动力不足，要么控制不力。另一方面，ONT/A在TMJD患者中的安全性尚未得到很好的评估，尽管临床前研究表明，在注射咀嚼肌后，下颌骨的形态发生了深刻的变化，牙槽骨丢失。为了解决这两个问题，我们提出了一项随机、双盲、安慰剂对照的临床试验(RCCT)，为期一个月的磨合，然后两个治疗相隔3个月，并进行3个月的随访。符合研究诊断标准的肌筋膜TMJD患者(每组51例)将被随机分配接受BONT/A或生理盐水载体注射。在第二个疗效随访期之后，被分配到BONT/A组的患者将被跟踪一个额外的治疗周期和3个月的随访期，以进一步评估与骨相关的变化。这项临床试验将确定单次和多次注射的效果。 Bont/A植入咬肌、颞肌和翼外肌，对(1)自发和诱发的疼痛强度，(2)咀嚼肌功能，(3)下颌骨和上颌骨的密度、体积和形态在支持后牙和下颌骨髁状突的区域的变化。RCCT的R34规划期将用于制定完整的协议和MOP，解决监管问题，获得IRB批准，计划数据安全监控，并最终确定基于锥束CT的详细协议，以评估指示潜在安全风险的骨相关变化。这项研究不仅满足了NIDCR支持创新临床研究以改善颅面健康的使命，而且还将提供对循证临床实践至关重要的关键信息，无论结果的方向如何。 公共卫生相关性：缺乏证据表明BONT/A是肌筋膜TMJD的安全或有效的治疗选择。因此，使用BONT/A治疗TMJD疼痛是一个潜在的公共卫生问题。这项研究不仅满足了NIDCR支持创新临床研究以改善颅面健康的目标，而且还旨在提供对循证临床实践至关重要的关键信息，而不考虑结果的方向。

DESCRIPTION (provided by applicant): While the literature provides little evidence that it is either safe or efficacious for this indication, Botulinum toxin A (BoNT/A) has received keen recent interest as a treatment option for patients with persistent myofascial temporomandibular muscle and joint disorder (TMJD). Were it shown to be safe and effective when injected into the masticatory muscles, it could prove invaluable to the many TMJD patients who do not respond to existing treatment modalities. Several studies have reported equivocal evidence of efficacy, but close inspection shows that those studies were either underpowered and/or poorly controlled. BoNT/A safety, on the other hand, has not been well assessed in TMJD patients, despite the fact that preclinical studies suggest profound changes in the morphology of the mandibular condyle and loss of alveolar bone following injection of the masticatory muscles. To address both of these issues, we propose a randomized, double-blind, placebo-controlled clinical trial (RCCT) with a one month run-in followed by two treatments spaced 3 months apart and a 3 month follow-up. Myofascial TMJD patients (51 per group) who meet Research Diagnostic Criteria will be randomly assigned to receive either BoNT/A or saline vehicle injections. After the second efficacy follow-up period, patients assigned to BoNT/A will be followed for an additional treatment cycle and 3 month follow-up period, to further assess bone-related changes. This clinical trial will determine the effect of single and repeated injections of BoNT/A into the masseter, temporalis and lateral pterygoid muscles on changes in (1) spontaneous and elicited pain intensity, (2) masticatory muscle function, and (3) density, volume and morphology of the mandible and maxilla in regions supporting the posterior teeth, as well as the mandibular condyle. The R34 planning period for this RCCT will be used to develop a full protocol and MOP, address regulatory issues, obtain IRB approval, plan for data safety monitoring, and finalize a detailed protocol for cone-beam CT based evaluation of bone-related changes indicating potential safety risks. This study not only satisfies NIDCR's mission to support innovative clinical research to improve craniofacial health, but it will also provide key information, regardless of the direction of the results, critical for evidence-based clinical practce. PUBLIC HEALTH RELEVANCE: Evidence that BoNT/A is either a safe or efficacious treatment option for myofascial TMJD is lacking. As such, use of BoNT/A for TMJD pain presents a potential public health issue. This study not only satisfies NIDCR's goal of supporting innovative clinical research to improve craniofacial health; it has also been designed to provide key information, regardless of the direction of the results, critical for evidence based clinical practce.