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

Pilot Placebo-Controlled Trial of Early Noninvasive Ventilation for ALS

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Device: BiPAP® S/T System; Other: sham-NIPPV

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Kirsten Gruis, MD, MS, University of Michigan

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: December 20, 2007
• First Posted (Estimate): December 24, 2007

Study Record Updates

• Last Update Posted (Estimate): July 10, 2013
• Last Update Submitted That Met QC Criteria: July 9, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: ALS; amyotrophic lateral sclerosis; FVC; NIPPV; nocturnal noninvasive positive pressure ventilation; forced vital capacity
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: R01NS55200