Polysomnography-directed Noninvasive Ventilation in Amyotrophic Lateral Sclerosis (ALS)

Progression of Respiratory Dysfunction in Amyotrophic Lateral Sclerosis (ALS) Patients: A Comparison of Standard of Practice vs Polysomnography-Directed Nocturnal Non-Invasive Positive Pressure Ventilation

Use of noninvasive ventilation (NIV, also known colloquially as "Bipap") has been associated in some studies with improvement in pulmonary function, quality of life and survival. NIV is typically applied during sleep, and without the benefit of sleep study to determine the optimal settings. The investigators have shown that when NIV is used in this fashion, failure of nocturnal oxygenation and ventilation is prominent. This study is randomizing patients to standard application of NIV vs application guided by use of sleep study data to determine the effect of titrated therapy on pulmonary function, quality of life and survival.

Study Overview

• Status: Terminated
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Other: Standard initiation of NIV; Other: Sleep study-guided adjustment of NIV

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of probable or definite Amyotrophic Lateral Sclerosis (ALS) per El Escorial criteria
• Between ages of 18 and 80 yrs old

Exclusion Criteria:

• Inability to clear secretions from the airway
• Life expectancy < 6 months from a comorbid condition
• Dementia sufficient to impair ability to use NIV, perform respiratory muscle pressure testing (PFTs), or complete Health-related Quality of Life (HRQOL) instruments
• Inability to follow up at the ALS Center on a regular basis
• Previously diagnosed obstructive Sleep Apnea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard NIV; Noninvasive ventilation (NIV) will be initiated and managed as per current standard of practice guided by the American Academy of Neurology (AAN) Practice Parameters (updated in 2009), in all subjects with amyotrophic lateral sclerosis (ALS) and a forced vital capacity of <50% predicted. Sleep studies will be performed at baseline, 2 weeks, 1, 3 and 6 months, but will not influence management of the NIV.	Other: Standard initiation of NIV; NIV will be initiated and managed as per current standard of practice. Sleep studies will be performed at baseline, 2 weeks, 1, 3 and 6 months to gather data but will not influence NIV management. NIV will be adjusted by a respiratory therapist or the subject's primary physician per waking symptoms.
Experimental: Sleep study titrated NIV; ALS subjects in this arm, who are offered NIV for Forced Vital Capacity (FVC) <50% as per AAN Practice Parameters, will have their initial level of NIV determined polysomnographically. They will be followed with sleep studies at 1 month, 3 months and 6 months to reassess NIV efficacy and NIV will be adjusted as necessary to optimize parameters of oxygenation and ventilation.	Other: Sleep study-guided adjustment of NIV; Sleep studies will be performed at baseline, within 2 weeks to initially titrate NIV, and at 1, 3 and 6 months to assess NIV performance and adjust it as necessary based on oxygenation and ventilation parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in spirometric, respiratory muscle strength, and gas exchange measures	FVC (forced vital capacity), FEV1 (forced expiratory volume in 1 second), MIP (maximum inspiratory pressure) and MEP (maximum expiratory pressure	Up to 6 months after starting NIV

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration that the Mental Component Summary (MCS) is maintained above 75% of baseline score for the Medical Outcomes Study Health Survey (SF-12)		Up to 6 months after starting NIV
Survival	Whether sleep study-titrated NIV is associated with trends to improved survival, compared with standardly prescribed (non-titrated) NIV	Up to 6 months after baseline
Nocturnal oxygenation and ventilation	Nadir oxygen saturation, number of oxygen desaturations of 3%/hr (ODI3), % time of sleep spent with oxygen saturation <90%, apnea-hypopnea index, asynchrony index	Up to 6 months after starting NIV
Modified Borg dyspnea score (see description)	The Modified Borg Dyspnea Scale is a 10-point Likert scale asking subjects to rate perceived shortness of breath, ranging from 0 (no breathlessness at all) to 10 (maximal breathlessness)	Up to 6 months after baseline

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: ALS Association
• Investigators: Principal Investigator: Robert C Basner, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: March 28, 2011
• First Submitted That Met QC Criteria: May 31, 2011
• First Posted (Estimate): June 2, 2011

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 10, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; Noninvasive Ventilation; Positive Pressure Ventilation; Respiratory Dysfunction
• 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: AAAC6753