Randomized controlled clinical trial of botulinum toxin for myofascial TMJD pain

描述（由申请人提供）：虽然文献中几乎没有证据表明其对该适应症安全或有效，但肉毒杆菌毒素A（BoNT/A）作为持续性肌筋膜颞下颌肌肉和关节疾病（TMJD）患者的治疗选择最近受到了极大的关注。如果它被证明是安全和有效的，当注射到咀嚼肌，它可以证明是无价的许多TMJD患者谁不响应现有的治疗方式。一些研究报告了疗效的模棱两可的证据，但仔细检查表明，这些研究要么是动力不足和/或控制不良。另一方面，BoNT/A的安全性尚未在TMJD患者中得到很好的评估，尽管临床前研究表明，注射咀嚼肌后，下颌髁突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，我们提出了一个随机，双盲，安慰剂对照的临床试验（RCCT），一个月的运行，随后两个治疗间隔3个月和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或生理盐水溶媒注射。在第二个疗效随访期后，将对分配到BoNT/A组的患者进行额外的治疗周期和3个月随访，以进一步评估骨相关变化。这项临床试验将确定单次和重复注射 BoNT/A进入咬肌、颞肌和翼外肌对（1）自发性和诱发性疼痛强度，（2）咀嚼肌功能，和（3）支持后牙的区域中的下颌骨和上颌骨以及下颌髁的密度、体积和形态的变化的影响。本RCCT的R34计划期将用于制定完整的方案和MOP，解决监管问题，获得IRB批准，计划数据安全性监测，并最终确定基于锥形束CT的骨相关变化评价的详细方案，提示潜在安全性风险。这项研究不仅满足了NIDCR的使命，以支持创新的临床研究，以改善颅面健康，但它也将提供关键信息，无论结果的方向，关键的循证临床实践。 公共卫生相关性：缺乏BoNT/A是肌筋膜TMJD安全或有效治疗选择的证据。因此，使用BoNT/A治疗TMJD疼痛存在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;它还旨在提供关键信息，无论结果的方向如何，对循证临床实践至关重要。

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.