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是前足溃疡和随后下肢截肢的高风险患者。目前，全接触铸造是治疗神经性足底溃疡最有效的方法，但当患者停止铸造时，溃疡复发率很高（20-70%）。足底溃疡与足底高压有关。有限的踝关节背屈被认为是导致前足足底压力高和收缩的原因。我们最近的随机对照试验发现，当全接触铸造联合腱-跟腱延长时，7个月时再骨折风险降低75%，2年时降低53%。术后前足峰值足底压力显著降低（27%），但在7个月内恢复到预处理水平。峰值压力的恢复与跖屈肌力量的恢复有关，而背屈运动范围在整个研究期间保持增加。我们推测，高足底压力的逐渐恢复允许最近愈合的组织适应压力并抵抗破坏。相比之下，仅接受完全接触石膏治疗的近期愈合组织立即遇到高足底压力，而没有这段适应期。由于前足压力的减少与踝关节力量的减少有关，而不是踝关节运动的增加，因此我们将研究注射肉毒杆菌毒素的新型治疗方法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减少溃疡复发。这项双盲、安慰剂对照、随机临床试验的具体目的是确定对糖尿病、周围神经病变和前足溃疡患者的胃-比目鱼肌注射肉毒毒素对1)溃疡愈合时间和溃疡复发率以及2)损伤、功能限制和残疾的影响，以及3)确定适当的肉毒毒素治疗剂量以达到最大的治疗效果。

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.