Botulinum Toxin Effects on Plantar Ulcer Recurrence

描述（由申请人提供）：糖尿病（DM）和周围神经病变患者发生前足溃疡和随后下肢截肢的风险较高。目前，全接触铸造是治疗神经性足底溃疡最有效的治疗方法，但当患者停止铸造时，溃疡复发率很高（20-70%）。足底溃疡与高足底压力有关。有限的踝关节背屈被认为有助于前足足底压力高和再溃疡。我们最近的随机对照试验发现，当全接触铸造结合跟腱延长术时，7个月时再骨折风险降低75%，2年时再骨折风险降低53%。术后前足足底压力峰值显著降低（27%），但在7个月内恢复到治疗前水平。峰值压力的恢复与跖屈肌力量的恢复相关，而背屈运动范围在整个研究期间保持增加。我们假设足底压力逐渐恢复，使最近愈合的组织能够适应压力并抵抗破坏。相比之下，那些接受完全接触石膏治疗的人的最近愈合的组织立即遇到了高足底压力，而没有这个适应期。因为前足压力的减少与踝关节力量的减少比踝关节活动的增加更相关，我们将研究肉毒杆菌毒素注射的新治疗用途是否可以暂时削弱跖屈肌，从而在不需要手术干预的情况下产生类似的溃疡复发减少。该双盲、安慰剂对照、随机临床试验的具体目的是确定肉毒杆菌毒素注射到患有DM、周围神经病变和前足溃疡的受试者的胃比目鱼肌中对1）溃疡愈合时间和溃疡复发率和2）损伤、功能限制和残疾的影响，以及3）确定肉毒杆菌毒素的适当治疗剂量以实现最大治疗效果。

DESCRIPTION (provided by applicant): Patients with diabetes mellitus (DM) and peripheral neuropathy are at high risk for forefoot ulcers and subsequent lower extremity amputation. Total contact casting currently is the most effective treatment for healing neuropathic plantar ulcers but ulcer recurrence is high (20-70%) when patients discontinue casting. Plantar ulcers are associated with high plantar pressure. Limited ankle dorsiflexion has been believed to contribute to high forefoot plantar pressure and reulceration. Our recent randomized controlled trial found a 75% reduction in risk of reucleration at 7 months and a 53% reduction at 2 years when total contact casting was combined with a tendo-achilles lengthening. Forefoot peak plantar pressure was substantially reduced (27%) post-operatively but returned to pretreatment level within 7 months. The return of peak pressure was associated with the return of strength in the plantarflexor muscles while dorsiflexion range of motion remained increased throughout the study period. We hypothesize that the gradual return of high plantar pressures allowed the recently healed tissue to adapt to the stress and resist breakdown. In contrast, the recently healed tissue of those receiving total contact cast treatment alone immediately encountered high plantar pressures without this period of adaptation. Because the reduction in forefoot pressure was more "elated to reduced ankle strength than increased ankle motion, we will investigate if the novel therapeutic use of botulinum toxin injections, can temporarily weaken the plantarflexor muscles to produce a similar reduction in ulcer recurrence without the need for surgical intervention. The specific aims of this double blinded, placebo-controlled, randomized clinical trial are to determine the effects of botulinum toxin injections into the gastroc-soleus muscle of subjects with DM, peripheral neuropathy, and a forefoot ulcer on 1) ulcer healing time and ulcer recurrence rate and 2) impairments, functional limitations, and disability, and to 3) determine the appropriate therapeutic dose of botulinum toxin to achieve maximal therapeutic outcomes.