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

• ClinicalTrials.gov Identifier: NCT00580593
• Recruitment Status: Completed
• First Posted: December 24, 2007
• Last Update Posted: July 10, 2013
• Sponsor: University of Michigan
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Kirsten Gruis, University of Michigan

Tracking Information

• First Submitted Date: December 20, 2007
• First Posted Date: December 24, 2007
• Last Update Posted Date: July 10, 2013
• Study Start Date: April 2007
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 29, 2010): 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. [ Time Frame: every three months, for the duration of the disease or as long as the person with ALS is able to participate in the study. ]
• Original Primary Outcome Measures (submitted: December 20, 2007): 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. [ Time Frame: over the treatment period ]

Current Secondary Outcome Measures (submitted: December 20, 2007)

• The SF-36 will be measured as a measure of quality of life. [ Time Frame: at baseline and every three months ]
• Pulmonary function tests including FVC will be measured. [ Time Frame: at baseline and every three months ]
• The ALS FRS will be used as a measure of functional outcome. [ Time Frame: at baseline and every three months ]
• The BDI/TDI (baseline and transition dyspnea indexes). [ Time Frame: 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. [ Time Frame: at baseline and every three months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of Early Noninvasive Ventilation for Amyotrophic Lateral Sclerosis (ALS)
• Official Title: Pilot Placebo-Controlled Trial of Early Noninvasive Ventilation for ALS
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis

Intervention

• 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 Name: Noninvasive Positive Pressure Ventilation (NIPPV)
• Other: sham-NIPPV
  a sham-device
  Other Name: placebo

Study Arms

• Active Comparator: 1
  Intervention: Device: BiPAP® S/T System
• Sham Comparator: 2
  Intervention: Other: sham-NIPPV

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 20, 2007): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 2012
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 79 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00580593
• Other Study ID Numbers: R01NS55200
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kirsten Gruis, University of Michigan
• Original Responsible Party: Kirsten Gruis, MD, MS, Assistant Professor, University of Michigan
• Current Study Sponsor: University of Michigan
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Kirsten Gruis, MD, MS; University of Michigan

• PRS Account: University of Michigan
• Verification Date: July 2013