Trial of Early Noninvasive Ventilation for Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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The goal of this trial is to determine the feasibility of conducting a randomized, double-blind, placebo-controlled trial of nocturnal noninvasive positive pressure ventilation in persons with amyotrophic lateral sclerosis with an forced vital capacity greater than or equal to 50 percent.

Detailed Description
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Amyotrophic lateral sclerosis (ALS) is an untreatable neurodegenerative disorder characterized by the progressive loss of motor neuron function. Respiratory failure is the most common cause of death in persons with ALS. Treatment of respiratory muscle weakness with nocturnal noninvasive positive pressure ventilation (NIPPV) when forced vital capacity (FVC) is less than 50 percent-but prior to the development of respiratory failure-has prolonged survival in observational studies. Despite the association of NIPPV use and survival, it is unknown whether earlier NIPPV treatment will benefit people with ALS. Also, no placebo-controlled studies of NIPPV treatment and people with ALS have been conducted. The goals of the this trial are to assess the feasibility of conducting a prospective, randomized, double-blind, clinical trial of NIPPV versus control (sham) NIPPV in people with ALS who have a FVC greater than 50 percent, and to gain preliminary data on outcome effects. In the trial, the investigators will test the following hypotheses: (1) People with ALS who have a FVC greater than 50 percent can tolerate active NIPPV and control NIPPV, and will find control NIPPV to be a believable treatment; (2) Initiation of active NIPPV in people with ALS who have a FVC greater than 50 percent will have better clinical outcomes with respect to measures of quality of life, rate of pulmonary function decline, and functional outcome; and (3) People with ALS who start active NIPPV early will have improved tolerance later when respiratory weakness has progressed. These aims will enable planning of a subsequent, large-scale and definitive clinical trial of early NIPPV (FVC greater than 50 percent) in people with ALS. If the benefits of early NIPPV can be confirmed, then a new treatment may be established for this progressive, fatal disease.

Official Title
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Pilot Placebo-Controlled Trial of Early Noninvasive Ventilation for ALS

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Device: BiPAP® S/T System
* Other: sham-NIPPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old Probable or possible ALS by El Escorial criteria If of child-bearing potential, has a negative urine or serum pregnancy test Exclusion Criteria: FVC < 50% predicted for age Previous pneumothorax Bullous emphysema Requirement for oxygen Previous use of any positive pressure ventilation equipment (continuous positive airway pressure, or bilevel positive airway pressure) Current involvement in a clinical treatment trial Any unstable medical condition thought likely to interfere with participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Device: BiPAP® S/T System<br>* The BiPAP® S/T System is a NIPPV device that provides intermittent ventilatory assistance to people with difficulty breathing secondary to respiratory muscle weakness.<br>* Other names: Noninvasive Positive Pressure Ventilation (NIPPV);|
| Sham Comparator: 2<br> | Other: sham-NIPPV<br>* a sham-device<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NIPPV adherence, as summarized by weekly means and standard deviations of hours of use for the two groups (active-NIPPV and sham-NIPPV). Additionally the patients' belief as to which treatment they believed they had tried will be assessed. |  | every three months, for the duration of the disease or as long as the person with ALS is able to participate in the study. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The SF-36 will be measured as a measure of quality of life. |  | at baseline and every three months | 
| Pulmonary function tests including FVC will be measured. |  | at baseline and every three months | 
| The ALS FRS will be used as a measure of functional outcome. |  | at baseline and every three months | 
| The BDI/TDI (baseline and transition dyspnea indexes). |  | at baseline and every three months | 
| Tolerance to standard NIPPV treatment during the observational phase of the study (after FVC has fallen below 50%) will also be summarized by weekly means and standard deviations of hours of use. |  | at baseline and every three months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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amyotrophic lateral sclerosis, ALS, nocturnal noninvasive positive pressure ventilation, NIPPV, forced vital capacity, FVC