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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Device: BiPAP® S/T System; Other: sham-NIPPV	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pilot Placebo-Controlled Trial of Early Noninvasive Ventilation for ALS
• Study Start Date: April 2007
• Actual Primary Completion Date: March 2012
• Actual Study Completion Date: March 2012

Arms and Interventions

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 Name: Noninvasive Positive Pressure Ventilation (NIPPV)
Sham Comparator: 2	Other: sham-NIPPV; a sham-device; Other Name: placebo

Outcome Measures

Primary Outcome Measures :

1. 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. ]

Secondary Outcome Measures :

1. The SF-36 will be measured as a measure of quality of life. [ Time Frame: at baseline and every three months ]
2. Pulmonary function tests including FVC will be measured. [ Time Frame: at baseline and every three months ]
3. The ALS FRS will be used as a measure of functional outcome. [ Time Frame: at baseline and every three months ]
4. The BDI/TDI (baseline and transition dyspnea indexes). [ Time Frame: at baseline and every three months ]
5. 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 ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Kirsten Gruis, Associate Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT00580593
• Other Study ID Numbers: R01NS55200
• First Posted: December 24, 2007
• Last Update Posted: July 10, 2013
• Last Verified: July 2013

Keywords provided by Kirsten Gruis, University of Michigan:

amyotrophic lateral sclerosis; ALS; nocturnal noninvasive positive pressure ventilation; NIPPV; forced vital capacity; FVC

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases