Effects of Nocturnal Non-invasive Ventilation in Patients With Amyotrophic Lateral Sclerosis

Effects of Early Intervention With Nocturnal Non-invasive Ventilation in Patients With Amyotrophic Lateral Sclerosis: A Randomized, Controlled Trial

Specific aims:

Aim 1. To determine the incidence of hypoventilation in Amyotrophic Lateral Sclerosis (ALS) patients.

Aim 2. To identify the clinical characteristics and risk factors associated .

Aim 3. To determine the effect of early intervention with nocturnal NIV on the prognosis of ALS patients.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Device: non-invasive ventilation

Detailed Description

Objectives: Amyotrophic lateral sclerosis is the commonest motor neuron disease with incidence of 0.8 person-years in Chinese. Respiratory muscle function has been proposed to be a strong predictor of quality of life (QoL) and survival in ALS. Some studies suggest that most patients with ALS developed hypoventilation when their vital capacity (FVC) is less than 50% of predicted value. However, the incidence of hypoventilation and factors associated with hypoventilation in ALS patients is not clear. Also, there is still no consensus as to which physiologic marker should be used as a trigger for the initiation of non-invasive ventilation (NIV) in ALS patients. The conflicts of studies come from variable subgroup of ALS, pulmonary function at enrollment, techniques used to diagnose ALS, time to apply NIV, and target endpoint. Therefore, this project aimed to study ALS patients who had relatively preserved respiratory muscle function and no respiratory failure at clinical to achieve three goals: (1) To determine the incidence of hypoventilation in ALS patients (2) To identify the clinical characteristics and risk factors associated with hypoventilation in ALS patients (3) To determine the effect of early intervention with NIV on the prognosis of ALS patients Study design: Randomized, controlled trial Participants: ALS patients whose FVC 40%-80% of predict, Pimax <60mmHg, and daytime PaCO2<50mmHg Protocol: Eligible patients with whole-night polysomnography (PSG) and transcutaneous CO2 (PtcCO2). Enrolled patients were randomized to standard treatment or NIV. The primary endpoint of prognosis was survival. The secondary endpoint was changes of PtcCO2 and PaCO2, unexpected admission or clinic visiting, daytime function and QoL.

Statistic: The baseline demographics of patients with or without hypoventilation were compared to determine the factors associated with hypoventilation in ALS patients. The impact of NIV in ALS patients was determined by comparing the primary and secondary goals between standard treatment and NIV group. A two-sided p value of < 0.05 was considered statistically significant.

Clinical implication: Hypoventilation at ALS patients who had relatively preserved respiratory muscle function and no respiratory failure at clinical sleep was common, early identification through PSG screening and PtcCO2 will allow for the early diagnosis and intervention. Understanding the time of applying NIV and the effect on prognosis in ALS will allow for the early intervention and prediction of outcomes.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Peilin Lee

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ALS patients who:

  • had FVC 40%-80% of predict
  • Pimax < 60 mmHg
  • daytime PaCO2 < 50 mmHg

Exclusion Criteria:

• Refuse to participate
• Require mechanical ventilation
• Active neurologic event other than ALS
• Obstructive pulmonary disease
• Active infection
• Need sedatives or narcotics within 3 days of sleep study
• Participating in other study at the same time

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2; ALS with non-invasive ventilation	Device: non-invasive ventilation; CPAP, BiPAP
No Intervention: 1; ALS without non-invasive ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes of PtcCO2 and PaCO2, admission or unexpected clinical visiting, and QoL	36 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Taipei Veterans General Hospital, Taiwan
• Investigators: Principal Investigator: Peilin Lee, M.D., National Taiwan University Hospital; Principal Investigator: Whey Dong Wu, M.D., Naitonal Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: February 8, 2009
• First Submitted That Met QC Criteria: August 12, 2009
• First Posted (Estimate): August 13, 2009

Study Record Updates

• Last Update Posted (Estimate): August 16, 2013
• Last Update Submitted That Met QC Criteria: August 14, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; hypoventilation
• 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: 200812112R; 2011-04-011LA (Other Identifier: Taipei Veterans General Hospital)