Clinical trial NCT03728803: Inspiratory Muscle Training in Nemaline Myopathy
Official title: Inspiratory Muscle Training in Patients With Nemaline Myopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nemaline Myopathy
Inspiratory Muscle Training
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2018-11-02
Enrollment: 42
Sex: ALL
Minimum age (years): 6
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A controlled before-after trial of inspiratory muscle training will be performed in patients with nemaline myopathy with respiratory muscle weakness. The 2 sequentially tested conditions are sham IMT and active IMT. Patients are not blinded to the conditions, instead patients are instructed that two training methods are tested. First the effect of breathing technique with low resistance (sham IMT) and secondly with high resistance (active IMT).
Primary purpose: SUPPORTIVE_CARE

Brief summary: Nemaline myopathy is a rare congenital myopathy. Respiratory failure is the main cause of death in these patients. The primary objective of this study is to determine the effect of a 8-week inspiratory muscle training program on respiratory muscle function in nemaline myopathy patients. The secondary objective is to determine respiratory muscle function in nemaline myopathy patients and its correlation with clinical severity and general neuromuscular function. The nemaline myopathy patients will be included in the first phase for a clinical characterization. From this phase patients will be selected for the second phase, which is a controlled before-after trial of inspiratory muscle training. The primary outcome is the change in maximal inspiratory pressure (MIP) after active inspiratory muscle training

Detailed description: Rationale: Nemaline myopathy is a group of congenital, hereditary neuromuscular disorders with variable symptoms such as muscle weakness, swallowing dysfunction, and dysarthria. Respiratory failure is the main cause of death in nemaline myopathy and occurs even in ambulant patients who otherwise appear to be only mildly affected; respiratory muscle weakness may even be the presenting feature. Inspiratory muscle training has shown to increase inspiratory muscle strength in patients with other neuromuscular disorders. It is hypothesized that inspiratory muscle training improves respiratory muscle function in nemaline myopathy patients with respiratory muscle weakness.

Objective: The primary objective is to determine the effect of a 8-week inspiratory muscle training program on respiratory muscle function in nemaline myopathy patients. The secondary objective is to determine respiratory muscle function in nemaline myopathy patients and its correlation with clinical severity and general neuromuscular function.

Study design: The study consist of two phases. Phase 1: A screening phase with an open design from which patients will be selected for the second phase. Phase 2: A controlled before-after trial of inspiratory muscle training. The 2 conditions tested are sham IMT and active IMT.

Study population: Nemaline myopathy patients from the local neuromuscular database will be recruited. Furthermore, other centres in the Netherlands will be contacted to expand the database of nemaline myopathy patients. Phase 2 requires 23 patients.

Intervention: Active IMT consists of 15 minutes of IMT, twice a day, 5 days per week for 8 weeks, at a training workload of 30% of MIP using a resistive inspiratory muscle training device. Sham IMT consists of similar training regime using a resistive inspiratory muscle training device where the resistance has been removed.

Main study parameters/endpoints: The primary outcome parameter is the change in maximal inspiratory pressure (MIP) after active inspiratory muscle training.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The intervention of inspiratory muscle training is not associated with any risks, but can be challenging in patients with respiratory muscle weakness to perform. There will be three visits to the hospital in 16 weeks. The first visit has a maximal duration of 6 hours (including breaks) and the other two visits 1.5 hour. During these visits several tests and physical examinations will be performed. Some of the tests may cause some physical discomfort, but none of them carry any risk. Patients may benefit from participating in this study by developing improved respiratory muscle function as a result of the inspiratory muscle training.

Eligibility criteria: Inclusion Criteria:

* genetically-confirmed nemaline myopathy (mutations in one of the genes causing nemaline myopathy: TPM3, NEB, ACTA1, TPM2, TNNT1, KBTBD13, CFL2, KLHL40, KHLH41, LMOD3, MYPN, RYR1)
* informed consent from participant or legal representative
* age-range: between the age of 6-80 years

Exclusion Criteria:

* history of another condition that affects respiratory muscle strength or function (e.g. COPD)

Primary outcomes:
measure: Change of maximal inspiratory pressure (cmH2O)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Secondary outcomes:
measure: Change of diaphragm thickness (mm)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of diaphragm thickening (ratio)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of diaphragm excursion (cm)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of peak cough flow (L/s)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of forced vital capacity (% predicted)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of forced expiratory volume in the first second (% predicted)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of peak expiratory flow (L/s)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of (Slow) vital capacity (% predicted)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of sniff nasal inspiratory pressure (cmH2O)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of maximal expiratory pressure (cmH2O)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Change of twitch mouth pressure (cmH2O)
timeFrame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
measure: Maximal voluntary contraction (N)
timeFrame: Baseline
measure: Rate of muscle relaxation (N/s)
timeFrame: Baseline
measure: Motor Function Measure test
timeFrame: Baseline
measure: 6-minute walk test
timeFrame: Baseline
measure: Falls
timeFrame: 100-day period from baseline on
measure: Mini-BESTest: Balance Evaluation Systems Test (Balance test for adults)
timeFrame: Baseline
measure: Pediatric Balance Scale (Balance test for children)
timeFrame: Baseline
measure: The RAND 36-Item Health Survey
timeFrame: Baseline
measure: Measurement model for the pediatric quality of life inventory: PedsQL
timeFrame: Baseline
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud university medical center
Study officials:
affiliation: Promotor
name: Baziel van Engelen, Prof. PhD
role: STUDY_DIRECTOR
References: