Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00560287
• Other study ID #: 190H09
• Secondary ID: 190H09
• Status: Recruiting
• Phase: Phase 4
• First received: November 16, 2007
• Last updated: March 26, 2010
• Start date: January 2008
• Est. completion date: August 2010

Study information

• Verified date: March 2010
• Source: Fondazione Salvatore Maugeri
• Contact: Stefano Nava, MD
• Phone: 0382 592
• Email: snava[@]fsm.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 2010
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Chronic Respiratory Failure
• Motor Neuron Disease
• Respiratory Insufficiency
• Sclerosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	Fondazione S.Maugeri	Pavia
Italy	Respiratory Unit FSM	Pavia

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Salvatore Maugeri

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	quality of life		1 year	No
Primary	tolerance to NIV		1 year	No
Primary	number of hours of NIV per day		1 year	No
Primary	frequency of hospital admission		1 year	No
Primary	frequency of changing the ventilator settings by the operator.		1 year	No
Secondary	survival		1 year	No
Secondary	diurnal and nocturnal gas exchange		1 year	No
Secondary	Pulmonary Function Tests (PFTs).		1 year	No