Optimizing INITIation of non invasive ventilation in ALS patients

Amyotrofic Lateral Sclerosis (ALS) is a disease with a downward slope with
respiratory insufficiency as primary cause of death. Chronic non-invasive
ventilation (NIV) is being suggested to most ALS patients in our country ,
however only 1/3 will actually start with it. Although some people do benefit,
in other patients the benefits are less clear. However it is hard to detect
benefit of the ventilatory support since the disease on its own is progressive
and will further impair the patient. The question arises why chronic
ventilatory support in ALS is provided on routinely base. The reason for this
is based on 1 randomized controlled trial including only 11 patients showing a
prolonged survival and a better preserved quality of life (QoL) in those with a
preserved bulbar function. However, another study showed that even in patients
with a bulbar dysfunction a survival benefit can be obtained. Despite this it
was recently showed in an uncontrolled design that the benefit of chronic NIV
might be less positive. The latter might be due to the fact that patients
started in this study group later, i.e. this patients had a lower vital
capacity and higher PaCO2 compared to the RCT.
In summary the clinical value of chronic NIV can be debated, there is only
moderate evidence for it, we do not know which (pheno)type of ALS patient is
the best candidate for, while the time of initiation may be crucial.
Furthermore the international recommendations when to start NIV in ALS patients
from different guidelines are expert-based, their advices are various and do
not take the different characteristics/ phenotypes of the ALS patients into
account
Based on these uncertainties the field is divided for knowledge and
appreciation and different opinions about chronic non-invasive ventilation
exist both in professionals and patients.

The primary objective of this study is to build a predictive model in which we
can identify which (pheno) type of ALS patients has the most benefit from NIV
in improving or maintaining quality of life.

Design: multi-centre prospective cohort study
Duration: The total duration of the study: 3,5 years. Inclusion period: 30
months. Follow up time : 9-1,5 months. Thereafter, 6 months will be used for
data analysis.
Setting: Involvement of all (4) HMV centres in the Netherlands.
Procedure:
During the first regular visit to the HMV centre patients will be asked to
participate in the study. Data will be recorded during regular visits to the
HMV centre. As part of the informed consent patients will be asked their
permission to retrieve the following clinical characteristics from their
medical record (from neurologist or rehabilitation specialist):
• Date of diagnosis
• Type of ALS at onset
• ALSFRS-R at the time of diagnosis
• Pulmonary function at the time of diagnosis
• Cognitive status (ECAS, ALS-FTD-Q) at onset
• Medical history

After informed consent is obtained the following data will be recorded:
First visit:
• Patient characteristics
• Questionnaires
• Pulmonary function

After the first visit patients will be allocated to one of the two cohorts:
• Cohort 1: patients who start NIV
• Cohort 2: patients who do not start NIV

Cohort 1:
Data will be record after 3,6 and 9 months.
• Patient characteristics
• Questionnaires
• Pulmonary function
8 Patients and 8 carers will be asked to take part in an interview

Cohort 2:
Data will be recorded every 3 months until initiation of NIV or death or max
during 1,5 years after the first visit to the HMV:
• Patient characteristics
• Questionnaires
• Pulmonary function
If a patient in cohort 2 will start with NIV, the patient will be transferred
to cohort 1.

There are no significant risks involved in taking part in this study. No risks
are related to the medical consultation assessments. The questionnaires may
cause some fatigue or discomfort. The respiratory measurements (spirometry,
blood gas and transcutaneous nocturnal gasexchange by SENTEC) are usual care.
We expect that only a very small number of patients will be asked to visit the
HMV centre more often than usual care.
There is no treatment for ALS and care is palliative. We hope that this
research will improve the care for ALS patients in relation to non-invasive
ventilation. Given the devastating nature of ALS we believe that the potential
benefit of the research justifies the minimal risks and burden in this study.