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.
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.
- 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
- 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