Clinical trial NCT00580593: Trial of Early Noninvasive Ventilation for Amyotrophic Lateral Sclerosis (ALS)
Official title: Pilot Placebo-Controlled Trial of Early Noninvasive Ventilation for ALS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: amyotrophic lateral sclerosis
ALS
nocturnal noninvasive positive pressure ventilation
NIPPV
forced vital capacity
FVC
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2007-12-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 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 outcomes:
measure: The SF-36 will be measured as a measure of quality of life.
timeFrame: at baseline and every three months
measure: Pulmonary function tests including FVC will be measured.
timeFrame: at baseline and every three months
measure: The ALS FRS will be used as a measure of functional outcome.
timeFrame: at baseline and every three months
measure: The BDI/TDI (baseline and transition dyspnea indexes).
timeFrame: at baseline and every three months
measure: 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.
timeFrame: at baseline and every three months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Kirsten Gruis, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jacobs TL, Brown DL, Baek J, Migda EM, Funckes T, Gruis KL. Trial of early noninvasive ventilation for ALS: A pilot placebo-controlled study. Neurology. 2016 Nov 1;87(18):1878-1883. doi: 10.1212/WNL.0000000000003158. Epub 2016 Aug 31.