Nemaline MyopathyNEMTRAINNCT03728803
Inspiratory Muscle Training in Nemaline Myopathy
A study testing Threshold IMT, Philips Respironics, Murrysville, PA, USA in people with Nemaline Myopathy and Inspiratory Muscle Training, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 80 years
- Conditions the study is for
- Nemaline Myopathy, Inspiratory Muscle Training
- What is being tested?
- Threshold IMT, Philips Respironics, Murrysville, PA, USA
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteNetherlands
- Study dates
- 10 Oct 2018to 25 Mar 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- history of another condition that affects respiratory muscle strength or function (e.g. COPD)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Inspiratory Muscle Training in Patients With Nemaline Myopathy
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
Read the 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.
- Conditions
- Nemaline Myopathy, Inspiratory Muscle Training
- Being tested
- Threshold IMT, Philips Respironics, Murrysville, PA, USA
- Medical subject headings
- Myopathies, Nemaline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Threshold IMT, Philips Respironics, Murrysville, PA, USADevice
Active inspiratory muscle training (IMT) by the threshold IMT provides consistent and specific pressure for inspiratory muscle strength and endurance training, regardless of how quickly or slowly patients breathe. This device incorporates a flow-independent one-way valve to ensure consistent resistance and features an adjustable specific pressure setting (in cmH20) to be set. When patients inhale through the Threshold IMT, a spring-loaded valve provides a resistance that exercises respiratory muscles through conditioning.
| Study group | Role | What they receive |
|---|---|---|
| Sham inspiratory muscle training | Sham comparator | Commercially available threshold IMT trainers (Threshold IMT, Philips Respironics) for inspiration will be used. For sham IMT the valve will be removed, creating a low resistance.
The participants will perform the sham IMT twice a day during 15 minutes for a period of 8 weeks. Receives: Device: Threshold IMT, Philips Respironics, Murrysville, PA, USA |
| Active inspiratory muscle training | Active comparator | Commercially available threshold IMT trainers (Threshold IMT, Philips Respironics) for inspiration will be used. After the sham IMT, the participants will perform an active inspiratory muscle training during 8 weeks with the same training schedule. The resistance will gradually be increased in the first couple of weeks until the intended resistance (30% of MIP) is reached. Receives: Device: Threshold IMT, Philips Respironics, Murrysville, PA, USA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of maximal inspiratory pressure (cmH2O)
Obtained with handheld device
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Secondary outcomes (20)
Change of diaphragm thickness (mm)
Obtained with ultrasound
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of diaphragm thickening (ratio)
Obtained with ultrasound
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of diaphragm excursion (cm)
Obtained with ultrasound
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of peak cough flow (L/s)
Obtained with handheld spirometry
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of forced vital capacity (% predicted)
Obtained with handheld spirometry
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of forced expiratory volume in the first second (% predicted)
Obtained with handheld spirometry
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of peak expiratory flow (L/s)
Obtained with handheld spirometry
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of (Slow) vital capacity (% predicted)
Obtained with handheld spirometry in sit and supine
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of sniff nasal inspiratory pressure (cmH2O)
Obtained with handheld device
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of maximal expiratory pressure (cmH2O)
Obtained with handheld device
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of twitch mouth pressure (cmH2O)
Measured after bilateral phrenic nerve stimulation
Measured: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Maximal voluntary contraction (N)
Handgrip ergonometer
Measured: Baseline
Rate of muscle relaxation (N/s)
Measured by transcranial magnetic stimulation
Measured: Baseline
Motor Function Measure test
The items of the MFM are classified in 3 domains:
D1: Standing and transfers (13 items, sub score range 0-39) D2: Axial and proximal motor function (12 items, sub score range 0-36) D3: Distal motor function (7 items, sub score range 0-21) Each item is scored on a 0-3 scale. Each sub score will be calculated as the percentage of total possible score achieved. Higher scores indicate a better outcome. The range of the total score is 0-96, again recalculated as the percentage of total possible score achieved.
Measured: Baseline
6-minute walk test
This test assesses distance walked over 6 minutes as a submaximal test of aerobic capacity/endurance. The outcome is compared to the reference values.
Measured: Baseline
Falls
The occurence of falls will be investigated retrospectively and prospectively during a 100-day period by questions composed by the investigators.
Measured: 100-day period from baseline on
Mini-BESTest: Balance Evaluation Systems Test (Balance test for adults)
This test consists of several domains of balance and consequently of several sub scores:
Anticipatory sub score 0-6 Reactive postural control 0-6 Sensory orientation sub score 0-6 Dynamic gait sub score 0-10
The sub scores are added up to a total score with a range of 0-28. Higher values represent a better outcome.
Measured: Baseline
Pediatric Balance Scale (Balance test for children)
This test consists of 14 item. The participant can score 0-4 on each item, with a maximum score of 56. Higher values represent a better outcome.
Measured: Baseline
The RAND 36-Item Health Survey
This questionnaire addresses eight concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health.
Scoring the RAND 36-Item Health Survey is a two-step process. First, precoded numeric values are recoded per the scoring key. All items are scored so that a high score defines a more favourable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are set at 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores. Hence, scale scores represent the average for all items in the scale that the respondent answered.
Measured: Baseline
Measurement model for the pediatric quality of life inventory: PedsQL
This questionnaire consists of 8 items on physical functioning, 5 items on emotional functioning, 5 items on social functioning, and 5 items on school functioning. Each item is scored on a 0-4 scale. The items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate a better outcome. To create the Psychosocial Health Summary Score, the mean is computed as the sum of the items over the number of items answered in the Emotional, Social, and School Functioning Scales. The Physical Health Summary Score is the same as the Physical Functioning Scale Score. To create the Total Scale Score, the mean is computed as the sum of all the items over the number of items answered on all the Scales.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2018
- Study start10 Oct 2018
- Primary completion25 Mar 2021
- Study completion25 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nemaline MyopathyStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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).
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Baziel van Engelen, Prof. PhD, Study director, Promotor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03728803
- Sponsor's protocol ID
- NL65214.091.18
- Acronym
- NEMTRAIN
- Status last verified
- Mar 2021
- First submitted
- 15 Oct 2018
- Last updated
- 5 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inspiratory Muscle Training in Patients With Nemaline Myopathy
- ClinicalTrials.gov ID
- NCT03728803
- Acronym / sponsor ID
- NEMTRAIN / NL65214.091.18
- Conditions
- Nemaline Myopathy, Inspiratory Muscle Training
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 10 Oct 2018 (actual)
- Primary completion
- 25 Mar 2021 (actual)
- Study completion
- 25 Mar 2021 (actual)
- First posted
- 2 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Sham inspiratory muscle training | Sham comparator | Device: Threshold IMT, Philips Respironics, Murrysville, PA, USACommercially available threshold IMT trainers (Threshold IMT, Philips Respironics) for inspiration will be used. For sham IMT the valve will be removed, creating a low resistance. The participants will perform the sham IMT twice a day during 15 minutes for a period of 8 weeks. |
| Active inspiratory muscle training | Active comparator | Device: Threshold IMT, Philips Respironics, Murrysville, PA, USACommercially available threshold IMT trainers (Threshold IMT, Philips Respironics) for inspiration will be used. After the sham IMT, the participants will perform an active inspiratory muscle training during 8 weeks with the same training schedule. The resistance will gradually be increased in the first couple of weeks until the intended resistance (30% of MIP) is reached. |
Who may qualify
- Ages
- 6 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- history of another condition that affects respiratory muscle strength or function (e.g. COPD)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Threshold IMT, Philips Respironics, Murrysville, PA, USAActive inspiratory muscle training (IMT) by the threshold IMT provides consistent and specific pressure for inspiratory muscle strength and endurance training, regardless of how quickly or slowly patients breathe. This device incorporates a flow-independent one-way valve to ensure consistent resistance and features an adjustable specific pressure setting (in cmH20) to be set. When patients inhale through the Threshold IMT, a spring-loaded valve provides a resistance that exercises respiratory muscles through conditioning. | Device | Active inspiratory muscle training, Sham inspiratory muscle training |
Primary outcome
Change of maximal inspiratory pressure (cmH2O)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Obtained with handheld device
20 secondary outcomes
Change of diaphragm thickness (mm)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of diaphragm thickening (ratio)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of diaphragm excursion (cm)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of peak cough flow (L/s)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of forced vital capacity (% predicted)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of forced expiratory volume in the first second (% predicted)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of peak expiratory flow (L/s)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of (Slow) vital capacity (% predicted)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of sniff nasal inspiratory pressure (cmH2O)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of maximal expiratory pressure (cmH2O)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Change of twitch mouth pressure (cmH2O)
Time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT
Maximal voluntary contraction (N)
Time frame: Baseline
Rate of muscle relaxation (N/s)
Time frame: Baseline
Motor Function Measure test
Time frame: Baseline
6-minute walk test
Time frame: Baseline
Falls
Time frame: 100-day period from baseline on
Mini-BESTest: Balance Evaluation Systems Test (Balance test for adults)
Time frame: Baseline
Pediatric Balance Scale (Balance test for children)
Time frame: Baseline
The RAND 36-Item Health Survey
Time frame: Baseline
Measurement model for the pediatric quality of life inventory: PedsQL
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Baziel van Engelen, Prof. PhD study director
Promotor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Threshold IMT, Philips Respironics, Murrysville, PA, USA in people with Nemaline Myopathy and Inspiratory Muscle Training, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of maximal inspiratory pressure (cmH2O) (time frame: Baseline, after 8 weeks sham IMT, after 8 weeks active IMT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.