Polysomnography-directed Noninvasive Ventilation in Amyotrophic Lateral Sclerosis (ALS)

Study Overview
=================
Brief Summary
-----------------
Use of noninvasive ventilation (NIV, also known colloquially as Bipap) has been associated in some studies with improvement in pulmonary function, quality of life and survival. NIV is typically applied during sleep, and without the benefit of sleep study to determine the optimal settings. The investigators have shown that when NIV is used in this fashion, failure of nocturnal oxygenation and ventilation is prominent. This study is randomizing patients to standard application of NIV vs application guided by use of sleep study data to determine the effect of titrated therapy on pulmonary function, quality of life and survival.

Official Title
-----------------
Progression of Respiratory Dysfunction in Amyotrophic Lateral Sclerosis (ALS) Patients: A Comparison of Standard of Practice vs Polysomnography-Directed Nocturnal Non-Invasive Positive Pressure Ventilation

Conditions
-----------------
Amyotrophic Lateral Sclerosis (ALS)

Intervention / Treatment
-----------------
* Other: Sleep study-guided adjustment of NIV
* Other: Standard initiation of NIV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of probable or definite Amyotrophic Lateral Sclerosis (ALS) per El Escorial criteria Between ages of 18 and 80 yrs old Exclusion Criteria: Inability to clear secretions from the airway Life expectancy < 6 months from a comorbid condition Dementia sufficient to impair ability to use NIV, perform respiratory muscle pressure testing (PFTs), or complete Health-related Quality of Life (HRQOL) instruments Inability to follow up at the ALS Center on a regular basis Previously diagnosed obstructive Sleep Apnea

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard NIV<br>Noninvasive ventilation (NIV) will be initiated and managed as per current standard of practice guided by the American Academy of Neurology (AAN) Practice Parameters (updated in 2009), in all subjects with amyotrophic lateral sclerosis (ALS) and a forced vital capacity of <50% predicted. Sleep studies will be performed at baseline, 2 weeks, 1, 3 and 6 months, but will not influence management of the NIV. | Other: Standard initiation of NIV<br>* NIV will be initiated and managed as per current standard of practice. Sleep studies will be performed at baseline, 2 weeks, 1, 3 and 6 months to gather data but will not influence NIV management. NIV will be adjusted by a respiratory therapist or the subject's primary physician per waking symptoms.<br>|
| Experimental: Sleep study titrated NIV<br>ALS subjects in this arm, who are offered NIV for Forced Vital Capacity (FVC) <50% as per AAN Practice Parameters, will have their initial level of NIV determined polysomnographically. They will be followed with sleep studies at 1 month, 3 months and 6 months to reassess NIV efficacy and NIV will be adjusted as necessary to optimize parameters of oxygenation and ventilation. | Other: Sleep study-guided adjustment of NIV<br>* Sleep studies will be performed at baseline, within 2 weeks to initially titrate NIV, and at 1, 3 and 6 months to assess NIV performance and adjust it as necessary based on oxygenation and ventilation parameters.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in spirometric, respiratory muscle strength, and gas exchange measures | FVC (forced vital capacity), FEV1 (forced expiratory volume in 1 second), MIP (maximum inspiratory pressure) and MEP (maximum expiratory pressure | Up to 6 months after starting NIV | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration that the Mental Component Summary (MCS) is maintained above 75% of baseline score for the Medical Outcomes Study Health Survey (SF-12) |  | Up to 6 months after starting NIV | 
| Survival | Whether sleep study-titrated NIV is associated with trends to improved survival, compared with standardly prescribed (non-titrated) NIV | Up to 6 months after baseline | 
| Nocturnal oxygenation and ventilation | Nadir oxygen saturation, number of oxygen desaturations of 3%/hr (ODI3), % time of sleep spent with oxygen saturation <90%, apnea-hypopnea index, asynchrony index | Up to 6 months after starting NIV | 
| Modified Borg dyspnea score (see description) | The Modified Borg Dyspnea Scale is a 10-point Likert scale asking subjects to rate perceived shortness of breath, ranging from 0 (no breathlessness at all) to 10 (maximal breathlessness) | Up to 6 months after baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amyotrophic Lateral Sclerosis, Noninvasive Ventilation, Respiratory Dysfunction, Positive Pressure Ventilation