EARLY TX OF ALS WITH NUTRITION AND NON-INVASIVE POSITIVE PRESSURE VENTILATION

通过营养和无创正压通气治疗 ALS 的早期 TX

• 批准号: 7627513
• 负责人: CARLAYNE E JACKSON
• 金额: $ 2.99万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627513
• 关键词: Amyotrophic Lateral Sclerosis; Anxiety; Bicarbonates; Blood Tests; Carbon Dioxide; Caregivers; Chloride Ion; Chlorides; Clinical; Computer Retrieval of Information on Scientific Projects Database; Data; Demographic Factors; Devices; Dietary Intervention; Disease; Dyspnea; Early Intervention; Enrollment; Ensure; Environmental air flow; Family; Fatigue; Functional disorder; Funding; Goals; Grant; Hour; Institutes; Institution; Invasive; Leg; Measurement; Measures; Medical Research; Medical Surveillance; Modality; Muscle function; Nose; Outcome; Oxygen saturation measurement; Participant; Patients; Pharmaceutical Preparations; Phase III Clinical Trials; Pilot Projects; Pulmonary function tests; Quality of life; Questionnaires; Research; Research Personnel; Resources; Respiratory Insufficiency; Respiratory Muscles; Sleep; Source; Spirometry; Stroke; Symptoms; United States National Institutes of Health; Upper arm; Visit; Week; base; clinically relevant; day; design; geriatric depression; improved; indexing; nervous system disorder; nutrition; pressure; psychologic; respiratory; social

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: To develop and validate strategies to improve tolerability of non-invasive positive pressure ventilation (NIPPV), to identify factors that influence acceptance of this treatment modality, and to evaluate measures of early respiratory dysfunction. RESEARCH PLAN: Subjects will be enrolled using a stratified design based on FVC 80-95% (Group 1) versus 50-79% (Group 2). NIPPV will be offered to participants as their FVC declines to the lower limit of their group (80% for Group 1 and 50% for Group 2). The results of this Pilot Study will allow the National Institute of Neurological Disorders and Stroke (NINDS) to design a multi-center Phase III trial to determine the efficacy of early NIPPV and nutritional intervention. METHODS: Spirometry will be performed and the FVC measures and patients will be stratified for Group 1 or 2. A physical exam will be performed and the following non-respiratory questionnaires will be administered: McGill Quality of Life, Geriatric Depression Scale, Idler Religiosity, Family Assessment Device, Spielberg Anxiety, and Chalder Fatigue Scale. The following respiratory questionnaires will be administered: Medical Research Council Modified Dyspnea Scale, Borg Dyspnea Scale, ALS Functional Dyspnea, Eppworth Sleepiness Scale, and the Pittsburgh Sleep Quality Index. The following pulmonary function tests (PFTs) will be performed: Spirometry, respiratory muscle pressures, maximum inspiratory pressures, and maximum expiratory pressures, sniff nasal pressure, maximum voluntary ventilation, end tidal CO2, and nocturnal oximetry. A blood test will be obtained to assess chloride and bicarbonate levels. Participants will be evaluated at 8 week intervals to ensure that their FVC does not dip below the set point to offer NIPPV. Patients in Group 1 (FVC between 85-90% of predicted) and Group 2 (FVC between 55 and 60% predicted) during any of their visits will be asked to return in 4 weeks for a "Surveillance" visit. Once subjects reach their goal FVC they will be started on nocturnal NIPPV and an additional questionnaire regarding NIPPV tolerance will be administered and data regarding compliance will be collected. Respiratory therapists will evaluate the subject and comparisons will be made between the PFTs to see which measure is most sensitive to changes in respiratory muscle function. Comparisons will be made between acceptors (NIPPV 4 hours/day) and refusers of NIPPV. We will seek to identify psychological, social, financial and demographic factors that predict delayed or non-acceptance of NIPPV. Differences in clinical involvement (bulbar vs. arm vs. leg), caregiver availability, ALSFRS, symptoms, interface, and medication usage will also be examined to determine factors that determine successful use and unsuccessful NIPPV use. CLINICAL RELEVANCE: Studies to date indicate that NIPPV improves survival in ALS, even when introduced late in the disease. It is hypothesized that early intervention may improve outcome even further. There is a lack of a reliable indicator for early respiratory insufficiency and factors need to be identified that influence acceptance and tolerability of NIPPV therapy and measurements of early respiratory dysfunction.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：开发和验证策略，以提高无创正压通气（NIPPV）的耐受性，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的措施。 研究方案：将采用分层设计，根据FVC 80-95%（第1组）与50-79%（第2组）入组受试者。 当受试者的FVC下降至其组别的下限（第1组为80%，第2组为50%）时，将向受试者提供NIPPV。 这项初步研究的结果将使国家神经疾病和中风研究所（NINDS）设计一项多中心III期试验，以确定早期NIPPV和营养干预的疗效。 方法：将进行肺功能测定，并将FVC指标和患者分为第1组或第2组。 将进行体格检查，并进行以下非呼吸问卷调查：麦吉尔生活质量、老年抑郁量表、Idler焦虑、家庭评估装置、Spielberg焦虑和Chalder疲劳量表。 将进行以下呼吸问卷调查：医学研究理事会改良呼吸困难量表、博格呼吸困难量表、ALS功能性呼吸困难量表、Eppworth嗜睡量表和匹兹堡睡眠质量指数。 将进行以下肺功能检查（PFT）：肺活量测定、呼吸肌压、最大吸气压和最大呼气压、鼻嗅压、最大自主通气量、潮气末CO2和夜间血氧测定。 将进行血液检查，以评估氯化物和碳酸氢盐水平。 将每隔8周对受试者进行一次评估，以确保其FVC不会低于提供NIPPV的设定点。 要求第1组（FVC在预测值的85-90%之间）和第2组（FVC在预测值的55 - 60%之间）的患者在任何访视期间在4周内返回进行“监测”访视。 一旦受试者达到其FVC目标，他们将开始接受夜间NIPPV，并将进行关于NIPPV耐受性的额外问卷调查，并收集关于依从性的数据。 呼吸治疗师将对受试者进行评估，并在PFT之间进行比较，以确定哪种测量对呼吸肌功能的变化最敏感。 将在接受者（NIPPV 4小时/天）和拒绝者之间进行比较。 我们将寻求确定预测延迟或不接受NIPPV的心理，社会，财务和人口因素。 还将检查临床受累（延髓vs.手臂vs.腿部）、护理人员可用性、ALSFRS、症状、接口和药物使用的差异，以确定决定成功使用和不成功使用NIPPV的因素。 临床相关性：迄今为止的研究表明，NIPPV可提高ALS患者的生存率，即使是在疾病晚期引入。 据推测，早期干预可能会进一步改善结果。 缺乏早期呼吸功能不全的可靠指标，需要确定影响NIPPV治疗的接受性和耐受性以及早期呼吸功能不全测量的因素。