Study of Standard Noninvasive Positive Pressure Ventilation (NIPPV) and Low Expiratory Pressure NIPPV in ALS Patients

Subjects will be randomized on a 1:1 basis to one of two groups differing in the sequence of
NIPPV settings ((a) standard, Bi-level NIPPV followed by IPAP-only NIPPV or (b) IPAP-only
NIPPV followed by standard, Bi-level, NIPPV). Subjects will then spend 6 weeks using the
first NIPPV set-up before crossing over to the other NIPPV treatment for 6 weeks. At the
beginning of the study, subjects will undergo approximately two hours of training and
education by a respiratory therapist regarding proper use of the Viasys® Healthcare,
Pulmonetic Systems, lap-top ventilators (LTV machine). They will be fitted with the
appropriate NIPPV set-up. The patients will use the same mask interface with the study NIPPV
machine that they were using with their NIPPV (bi-level positive airway pressure (BiPAP))
machine prior to study entry.

The patients will have two additional study visits after the consent/training session: one
at the end of 6 weeks, after the first NIPPV treatment period (prior to crossing over to the
second NIPPV treatment), and the second at the end of 12 weeks, after the second NIPPV
treatment period.

NIPPV usage will be recorded as hours of use as measured objectively by the NIPPV machine
hour meter. When the patient returns for his/her first study visit at the end of week six,
the NIPPV machine hour meter will be recorded by the study investigator. By subtracting the
hours recorded at the beginning of week two from the hours recorded at the end of week six,
the NIPPV hours of usage for weeks two, three, four, five and six will be obtained. This
same procedure will be repeated to record NIPPV hours of usage for the beginning of week
eight and the end of week twelve to measure the hours of usage with the second NIPPV set-up
for weeks eight, nine, ten, eleven and twelve. This allows study subjects one week to adjust
to the new pressure settings of each treatment arm.

Dyspnea as measured by the baseline dyspnea index/ transition dyspnea index (BDI/TDI), and
quality of life as measured by the EuroQol Visual analogue scale(VAS) will be
re-administered at both 6 and 12 week study visits by study personnel. Lastly, patient
preference of NIPPV treatment will be subjectively assessed at the 12 week study visit on a
Likert scale (definitely first treatment, probably first treatment, no preference, probably
second treatment, definitely second treatment).

Inclusion Criteria:

1. Age greater than 18 years

2. Definite or probable ALS by El Escorial criteria

3. Maximal inspiratory force < 60 cm/H2O or FVC <50% predicted (American College of
Chest Physicians' criteria for initiating NIPPV)

4. Patients must have used NIPPV (typically administered as BiPAP) for at least 2
months

5. Currently using NIPPV ≥5 days a week with an EPAP = 4 cm H2O.

Exclusion Criteria:

1. Any medical condition that will interfere with participation

2. Inability to consent for him/herself

3. Known obstructive sleep apnea or obstructive pulmonary disease.