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

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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 dysfuncti