Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis

Role of Non-invasive Ventilation in Amyotrophic Lateral Sclerosis: Volume Versus Pressure Mode

Non-invasive mechanical ventilation (NIV) has been increasingly used as a treatment of chronic hypercapnic respiratory failure. Its use in patients affected by chronic obstructive pulmonary disorders is still controversial, while most of the studies performed in restrictive thoracic disorders (RTD), and in particular in neuromuscular patients, suggested alleviation of the symptoms of chronic hypoventilation in the short term, and in two small studies survival was prolonged.

In the terminal phase of the disease, when the respiratory muscles became weaker it is very likely that the operators need to frequently adjust the level of inspiratory pressure in an attempt to guarantee an adequate tidal volume, so that alveolar hypoventilation may be avoided.

Theoretically the use of a volume assisted ventilation may overpass this problem of frequent variations of the settings, since the provision of a fixed tidal volume may always guarantee and adequate alveolar ventilation.

The primary aims of this multicenter randomized study are to evaluate the clinical efficacy, the patients' tolerance and quality of life and the frequency of changing settings in a group of patients with SLS and initial chronic respiratory failure undergoing long-term NIV with Pressure Support Ventilation or Volume Assisted Ventilation.

Study Overview

• Status: Unknown
• Conditions: Amyotrophic Lateral Sclerosis; Chronic Respiratory Failure
• Intervention / Treatment: Device: Non invasive ventilation delivered with one of the ventilator specifically designed for NIV and given to the patient by the home care providers; Device: Non invasive ventilation

Detailed Description

Background

Non-invasive mechanical ventilation (NIV) has been increasingly used as a treatment of chronic hypercapnic respiratory failure. Its use in patients affected by chronic obstructive pulmonary disorders is still controversial, while most of the studies performed in restrictive thoracic disorders (RTD), and in particular in neuromuscular patients, suggested alleviation of the symptoms of chronic hypoventilation in the short term, and in two small studies survival was prolonged. As a matter of fact a recent Cochrane review stated that "long-term mechanical ventilation should be offered as a therapeutic option to patients with chronic respiratory failure due to neuromuscular diseases". Recurrent episodes of nocturnal desaturation especially during REM sleep may deeply influence the prognosis of patients affect by these disorders (i.e. ALS), and they are often associated with hypercapnia, so that the correction of nocturnal hypoventilation seems to be the major goal to achieve with the ventilatory treatment.

A very recent randomized controlled trial show that in ALS without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life, including sleep quality. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy, like riluzole.

Most of the studies performed in RTD disorders were performed using a pressure assisted mode (i.e Pressure Support Ventilation), because of the supposed better tolerance of the patients and easy of settings for the operators, even though this has never been scientifically proven.

In the terminal phase of the disease, when the respiratory muscles became weaker it is very likely that the operators need to frequently adjust the level of inspiratory pressure in an attempt to guarantee an adequate tidal volume, so that alveolar hypoventilation may be avoided.

Theoretically the use of a volume assisted ventilation may overpass this problem of frequent variations of the settings, since the provision of a fixed tidal volume may always guarantee and adequate alveolar ventilation.

The primary aims of this multicenter randomized study are to evaluate the clinical efficacy, the patients' tolerance and quality of life and the frequency of changing settings in a group of patients with SLS and initial chronic respiratory failure undergoing long-term NIV with Pressure Support Ventilation or Volume Assisted Ventilation.

Aim of the Project

The primary aims of the project are to evaluate the clinical efficacy, the patients' tolerance and quality of life and the frequency of changing settings in a group of patients with SLS and initial chronic respiratory failure undergoing long-term NIV with Pressure Support Ventilation or Volume Assisted Ventilation.

• Enrollment criteria: Patients with the diagnosis of ALS and one of the following signs: 1) Vital Capacity < 50% predicted 2) a Maximal Inspiratory Pressure (MIP) < 60% predicted 3) polygraphic signs of nocturnal hypoventilation with daytime symptoms.

- The patients will be randomized to receive NIV with one of the following modes: 1) Pressure Support Ventilation with the inspiratory pressure set according to the patient's tolerance in order to achieve an expired tidal volume > 6 ml/Kg and <8ml/Kg. The back-up rate will be set at 10 breaths/min. 2) Volume assist ventilation with a back-up rate of 10 breaths/min and a tidal volume set to achieve an expired tidal volume > 6 ml/Kg and <8ml/Kg

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione S.Maugeri
    • Contact: Stefano Nava, md; Phone Number: o3825921; Email: snava@fsm.it
    • Contact: Stefano Nava, md; Phone Number: 03825921; Email: snava@fsm.it
  • Pavia, Italy, 27100
    • Not yet recruiting
    • Respiratory Unit FSM
    • Contact: Stefano Nava, md; Phone Number: 806 0382 592; Email: snava@fsm.it
    • Contact: Francesco Fanfulla, MD; Phone Number: 815 0382 592; Email: ffanfulla@fsm.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with the diagnosis of ALS and one of the following signs:

  • Vital Capacity < 50% predicted
  • A Maximal Inspiratory Pressure (MIP) < 60% predicted
  • Polygraphic signs of nocturnal hypoventilation with daytime symptoms.

Exclusion Criteria:

• Life expectancy>12 months
• Any comorbidity
• Acute Respiratory Failure

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: 1; Volume assist non-invasive ventilation	Device: Non invasive ventilation delivered with one of the ventilator specifically designed for NIV and given to the patient by the home care providers; A very recent randomized controlled trial show that in ALS without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life, including sleep quality. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy, like riluzole.; Other Names: Legendaire (Airox); Vivo (Breas); Elisee (Saime); Synchrony (Respironics); Device: Non invasive ventilation; A very recent randomized controlled trial show that in ALS without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life, including sleep quality. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy, like riluzole.; Other Names: Legendaire (Airox); Vivo (Breas); Elisee (Saime); Synchrony (Respironics)
Active Comparator: 2; Pressure Assist mode	Device: Non invasive ventilation delivered with one of the ventilator specifically designed for NIV and given to the patient by the home care providers; A very recent randomized controlled trial show that in ALS without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life, including sleep quality. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy, like riluzole.; Other Names: Legendaire (Airox); Vivo (Breas); Elisee (Saime); Synchrony (Respironics); Device: Non invasive ventilation; A very recent randomized controlled trial show that in ALS without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life, including sleep quality. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy, like riluzole.; Other Names: Legendaire (Airox); Vivo (Breas); Elisee (Saime); Synchrony (Respironics)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
quality of life	1 year
tolerance to NIV	1 year
number of hours of NIV per day	1 year
frequency of hospital admission	1 year
frequency of changing the ventilator settings by the operator.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
survival	1 year
diurnal and nocturnal gas exchange	1 year
Pulmonary Function Tests (PFTs).	1 year

Collaborators and Investigators

• Sponsor: Fondazione Salvatore Maugeri
• Investigators: Principal Investigator: Stefano Nava, Fondazione Salvatore Maugeri; Principal Investigator: Stefano Nava, MD, Fondazione S.Maugeri

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Anticipated): August 1, 2010

Study Registration Dates

• First Submitted: November 16, 2007
• First Submitted That Met QC Criteria: November 16, 2007
• First Posted (Estimate): November 19, 2007

Study Record Updates

• Last Update Posted (Estimate): March 29, 2010
• Last Update Submitted That Met QC Criteria: March 26, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; Non-invasive ventilation; Chronic Respiratory Failure
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Respiratory Insufficiency; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: 190H09