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

Study Overview
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Brief Summary
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The purpose of the study is to test whether noninvasive positive pressure ventilation (NIPPV) without expiratory positive airway pressure (EPAP) (inspiratory positive airway pressure (IPAP)-only) will result in an increase in patient usage of NIPPV compared with standard, Bi-level NIPPV. Secondarily, the investigators will assess measures of dyspnea, quality of life, patient satisfaction, and side effects.

Detailed Description
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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 transition dyspnea index (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).

Official Title
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A Randomized Crossover Study of Standard, Noninvasive Positive Pressure Ventilation (NIPPV) and Low Expiratory Pressure NIPPV in Amyotrophic Lateral Sclerosis (ALS) Patients

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Device: Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years Definite or probable ALS by El Escorial criteria Maximal inspiratory force < 60 cm/H2O or FVC <50% predicted (American College of Chest Physicians' criteria for initiating NIPPV) Patients must have used NIPPV (typically administered as BiPAP) for at least 2 months Currently using NIPPV ≥5 days a week with an EPAP = 4 cm H2O. Exclusion Criteria: Any medical condition that will interfere with participation Inability to consent for him/herself Known obstructive sleep apnea or obstructive pulmonary disease.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bi-level, standard, NIPPV<br>Standard NIPPV with both an inspiratory and expiratory positive airway pressure. | Device: Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine)<br>* Noninvasive positive airway pressure ventilation<br>|
| Experimental: IPAP-only, NIPPV<br>NIPPV with only inspiratory positive airway pressure, no expiratory positive airway pressure | Device: Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine)<br>* Noninvasive positive airway pressure ventilation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hours of NIPPV Usage | Patients experienced the first intervention period during weeks 1-6 and the second intervention period during weeks 7-12. Patients were given one week to learn how to use the NIPPV equipment at the beginning of each intervention period. Therefore, only the total NIPPV hours used during the last 5 weeks of each intervention period were collected and divided by the number of weeks to obtain the average, weekly hours of NIPPV usage assessed at 6 weeks (first intervention) and 12 weeks (second intervention) for each patient. | Assessed at 6 weeks (first intervention) and 12 weeks (second intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Preference (Likert Scale) Definitely IPAP-only Probably IPAP-only Uncertain Probably Bi-level Definitely Bi-level | Patient Preference of NIPPV mode: definitely IPAP-only probably IPAP-only uncertain probably Bi-level definitely Bi-level Number of patients who chose definitely or probably are reported. | Assessed at 6 weeks (first intervention) and 12 weeks (second intervention) | 
| Transitional Dyspnea Index | Transitional Dyspnea Index scores patient reported changes in difficulty breathing during each intervention period from -3 (major deterioration) to +3 (major improvement) in three categories: functional impairment, magnitude of task, and magnitude of effort. The total TDI score ranges from -9 to +9. | Assessed at 6 weeks (first intervention) and 12 weeks (second intervention) | 
| EuroQol Visual Analogue Scale(VAS) | Quality of life assessed with visual analogue scale. Where the patient is asked to place a mark on a piece of paper with a vertical, scale from 100 at the top to 0 at the bottom of the scale. Where the patient is informed that 100 represents his or her best imaginable health state and 0 is his or her worst imaginable health state. | Assessed at 6 weeks (first intervention) and 12 weeks (second intervention) |