Inspiratory Muscle Training in Myotonic Dystrophy type 1: a pilot study.

Respiratory failure is the primary cause of mortality in Myotonic Dystrophy
type 1 (DM1), which is mainly caused by respiratory muscle weakness.
Atelectasis and pneumonia are additional risk factors for death occurring at a
mean age of 54 years. Daily life activities are mainly limited due to fatigue
and muscle weakness, being present in more than 90% of patients. As curative
treatment is not available for DM1 patients yet, main treatment goals are to
relieve complaints and to improve quality of life.
In case of the development of hypercapnic respiratory failure, current
treatment option is only home mechanical ventilation (HMV), which improves
gas-exchange but with variable effects on symptom relieve and unclear survival
benefits. Patients often experience mask fitting problems and lack of symptom
improvement which both result in decreased treatment motivation and
consequently leads to insufficient or prematurely stopping of HMV. Thus, there
is a need to search for new treatment modalities for DM1 patients with
respiratory failure.
A new treatment modality could be training of the impaired respiratory muscles
by inspiratory muscle training (IMT) to improve muscle strength or at least
delay progression of respiratory muscle weakness. It seems paradoxical to
exercise affected muscles in patients with progressive muscle atrophy, but
training programs of the skeletal muscles in DM1 shows in general small to
moderate benefits by increasing muscle endurance, aerobic capacity, and maximal
strength. Additional, muscle growth is confirmed by biopsies and imaging
studies. Adverse effects of training are not described.
To our best knowledge only two small case series and one case report about IMT
in DM1 patients exist, which showed improvement of respiratory muscle strength
after completed training period. IMT studies are mainly performed in patients
with chronic obstructive pulmonary disease, in which improvement in respiratory
muscle strength and endurance capacity are found. Also in several other
neuromuscular disorders positive effects of IMT are described. In neuromuscular
disorders (mainly spinal muscular atrophy and children with Duchenne)
improvement of endurance respiratory muscle training, and respiratory muscle
strength are found. Based on these results we hypothesize that IMT training in
DM1 patients will improve respiratory muscle function, which probably could
prevent the development of atelectasis and pneumonia or even delay the need for
HMV.

In this pilot study of ten DM1 patients, we aim to investigate primarily
whether IMT on a 12-week home based personalized training schedule using a
POWERbreathe KHP2 could improve respiratory muscle strength and endurance
capacity. Secondary its effects on cough symptoms, pulmonary function, quality
of life, respiratory muscle function (ultrasound of diaphragm) will be
investigated.

Primary Objective:
To study in detail whether a 12-week home based personalized IMT training
scheme using the POWERbreathe KHP2 in DM1 patients could result in improvement
of maximum inspiratory pressure (PImax) and endurance capacity. We postulate
that a positive outcome of this pilot study could be defined as reaching at
least 20% improvement in both PImax and endurance capacity in at least five of
ten patients.

Secondary Objective(s):
Additional, we will investigate the effects of training on some clinically
outcome parameters: cough and fatigue, quality of life and lung volumes. Direct
effects of training on the respiratory muscle function (activity, movement and
thickness of the diaphragm) will be measured by ultrasound.

This study is a single arm intervention pilot study of ten DM1 patients,
investigating the effects of IMT on inspiratory muscle strength and endurance
capacity.
Adult DM1 patients, who have reduced PImax and vital capacity (both <80% of
predicted) without need or indication for HMV will be asked to participate for
this study. Before starting a training schedule patients will undergo
additional tests at baseline to measure pulmonary function (including
inspiratory muscle strength and endurance capacity), ultrasound of diaphragm
and symptoms based on questionnaires.
A personalized training schedule will be prepared in collaboration with a
physiotherapist. Training sessions consist of 30 breaths, using a
POWERbreatheKHP2, at least 10 sessions per week (5 days per week, one session
in the morning and one session in the evening). One session takes circa 3-5
minutes.
Training intensity will start on 20% of baseline PImax and will be increased
every two weeks during a supervised training session until 50% of baseline
PImax in the final two weeks of the schedule. Data about training sessions that
have been done at home are stored on the trainer (anonymized). Data of power
and work of breathing per breathing session in combination with a patients*
diary will be used to increase training intensity during supervised training
sessions.
After 12 weeks of training all previously described tests will be tested
again.

The first and last visit to the hospital will takes circa 4h to perform all
investigations.
Every two weeks a supervised training session will be done in the hospital,
which will take circa 30 minutes.

Benefits:
Subjects can improve their inspiratory muscle strength and endurance capacity
by participating in this IMT study. If therapy will be continued afterwards
these improvements could subsequently result in decrease of cough / dyspnoea
symptoms and decreases the risks of atelectasis and pneumonia. The development
of respiratory failure (and needs for HMV) could also be delayed

Risk assessment
Patients can experience some short term side effects like dizziness, fatigue or
some myalgia due to the training sessions, which should disappear soon after
the training session.
Due to the natural burden of DM1 with progressive muscle weakness a theoretical
potential risk could be that muscle strength and endurance capacity will
decrease instead of increase. However, in other neuromuscular disorders
(Duchenne, ALS), this is not described.

Group relatedness
Indirect benefits of this study might be achieved, because at a group level we
will learn more about effects of training on respiratory muscles in DM1. The
gained knowledge will help to develop future studies and new treatment
modalities.

Time schedule:
The first and last visit to the hospital will takes circa 4h to perform all
investigations.
Patients have to do their home training sessions daily, at least 10 sessions
per week, which will take circa 10 minutes per day.
Every two weeks a supervised training session will be done in the hospital,
which will take circa 30 minutes.