Early Treatment of ALS with Nutrition and NIPPV

迄今为止的研究表明，经皮内镜胃造口术（PEG）和非侵入性阳性 压力通气（NIPPV）可改善肌萎缩侧索硬化症（ALS）患者的生存率， 在疾病晚期引入。我们推测早期干预可能会进一步改善结果。 然而，关于这些治疗的早期使用的许多问题排除了III期临床试验的设计。 来检验这个假设。NIPPV和营养的共同点是缺乏早期营养不良的可靠指标。 呼吸或营养不足。在营养方面，我们需要可靠和具有成本效益的方法， 以确定患者在疾病的不同阶段期间的能量（即热量）需求，并基于 PEG关于能量摄入充足性的建议。对于NIPPV，我们需要确定 影响该疗法的接受性和耐受性以及早期呼吸功能障碍的测量。 因此，我们提出了这项多中心的初步研究，以开发一个defmitive III期试验的方法。的 本初步研究的具体目的是：1）开发和验证改善药物耐受性的策略。 NIPPV，以确定影响接受这种治疗方式的因素，并评估 早期呼吸功能障碍; 2）开发和验证确定ALS能量平衡的方法。 在本项初步研究中，所有11家研究中心将采用基于FVC的分层设计（80-95% vs 50- 95%）招募患者。 79%），并在下降至该FVC水平的下限时提供NIPPV。六个站点将收集更多 详细信息，以批判性地评价NIPPV的可接受性，制定改善耐受性的策略，以及 验证这种方法，并收集呼吸测量结果，以便更早地识别 失败其他5个研究中心将在纵向设计中使用“金标准”双标记水方法 推导出经验方程，以基于容易进行的临床试验可靠地预测个体能量需求， 措施这项试点研究的结果将使我们能够开发和验证方法，以便我们能够设计 一项多中心III期临床试验，旨在确定早期NIPPV和营养干预的疗效。在 此外，我们的结果将立即适用于临床医生在实践中使用，并将提供基础 重新制定未来ALS药物试验的实验设计。

Studies to date indicate that Percutaneous Endoscopic Gastrostomy (PEG) and Non-Invasive Positive Pressure Ventilation (NIPPV) improve survival in Amyotrophic Lateral Sclerosis (ALS), even though introduced late in the disease. We hypothesize that early intervention may improve outcome even further. However, many issues regarding the early use of these treatments preclude the design of a Phase III clinical trial to test this hypothesis. Common to both NIPPV and nutrition is a lack of a reliable indicator of early respiratory or nutritional insufficiency. With respect to nutrition, we need reliable and cost effective methods to determine a patient's energy (i.e. caloric) requirements during different stages of the illness and base the recommendation for PEG on the adequacy of energy intake. For NIPPV, we need to identify factors that influence acceptance and tolerability of this therapy, and measurements of early respiratory dysfunction. Therefore, we propose this multicenter Pilot Study to develop methods for a defmitive Phase III trial. The Specific Aims of this Pilot Study are: 1) To develop and validate strategies to improve tolerability of NIPPV, to identify factors that influence acceptance of this treatment modality, and to evaluate measures of early respiratory dysfunction; and 2) To develop and validate methods to determine energy balance in ALS. In this Pilot Study, all 11 sites will enroll patients using a stratified design based on FVC (80-95% vs 50- 79%) and offer NIPPV as they decline to the lower limit of this FVC level. Six sites will collect additional detailed information to critically evaluate acceptability of NIPPV, devise strategies to improve tolerance, and validate this approach as well as collect respiratory measurements that may allow earlier identification of failure. The other 5 sites will use the "gold standard" Doubly Labeled Water method in a longitudinal design to derive empiric equations to reliably predict individual energy needs based on easily performed clinical measures. The results of this Pilot Study will allow us to develop and validate methods so that we can design a multicenter Phase III trial to determine the efficacy of early NIPPV and nutritional intervention. In addition, our results will be immediately applicable for use by clinicians in practice and will provide the basis to re-formulate the experimental design of future drug trials in ALS.