Nemaline Myopathy Type 6NCT03211923
Muscle Relaxation in Myopathies With Positive Muscle Phenomena
An observational study of Nemaline Myopathy Type 6 and Myotonic Dystrophy Type 2, run by Radboud University Medical Center.
Trial summary
The aim of this study is to quantify muscle relaxation properties of the finger flexor muscles in patients with different myopathies. The inhibiting effects of transcranial magnetic stimulation (TMS) on the cortical motor hand area are used to induce relaxation, which in turn will be monitored with handgrip… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nemaline Myopathy Type 6, Myotonic Dystrophy Type 2, McArdle Disease
- What is being tested?
- Transcranial magnetic stimulation (TMS)
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 5 Jan 2017to 31 Dec 2019
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Diagnosis of one of the following myopathies: Nemaline myopathy type 6 (NEM6), Myotonic dystrophy type 2 (DM2), McArdle disease. Patients will be selected from a local database at the Radboud University Medical Center. The goal is to include 5 men and 5 women per myopathy.
Who may be able to join
- Diagnosis of one of the following myopathies: Nemaline myopathy type 6 (NEM6), Myotonic dystrophy type 2 (DM2), McArdle disease.
Who cannot join
- Pregnancy
- Serious head trauma or brain surgery
- Large or ferromagnetic metal parts in the head
- Implanted cardiac pacemaker or neurostimulator
- Epilepsy, convulsion or seizure
- Use of medication that can influence muscle relaxation or cortical excitability
About this study
Official title: Muscle Relaxation Properties in Myopathies With Positive Muscle Phenomena: a Study Using Transcranial Magnetic Stimulation
The aim of this study is to quantify muscle relaxation properties of the finger flexor muscles in patients with different myopathies. The inhibiting effects of transcranial magnetic stimulation (TMS) on the cortical motor hand area are used to induce relaxation, which in turn will be monitored with handgrip dynamometry and EMG. The investigators will evaluate if this technique can be implemented as a diagnostic tool in clinical practice.
Muscle relaxation is an often overlooked property of the muscle as compared to muscle strength or activation. Muscle relaxation is affected in different myopathies, such as myotonic dystrophy, non-dystrophic myotonias, and Brody myopathy. Therefore, a diagnostic tool to quantify muscle relaxation is of clinical and scientific importance. In this study, transcranial magnetic stimulation (TMS) is used, in combination with a dynamometer to quantify muscle relaxation properties.
Read more
Transcranial magnetic stimulation (TMS) is a non-invasive technique that is commonly used to stimulate the brain. In practice, a circular coil is held directly above the scalp, upon which a strong current pulse induces a magnetic field that stimulates the underlying superficial brain areas. This stimulation can have both activating and inhibiting effects.
When the motor cortex (i.e. the area of the brain that controls muscle contractions) is strongly stimulated with TMS during a voluntary muscle contraction, both excitatory and inhibitory effects can be observed in the muscle the targeted cortical area controls. The inhibitory effect entails a transient interruption of neural drive to the muscle. This interruption, called the "silent period", lasts for less than half a second and results in the relaxation of the muscle. Muscle activity and control quickly return to normal after the silent period.
The elegance and main advantage of TMS-induced muscle relaxation lies in the fact that it excludes all voluntary influences on the relaxation process. Furthermore, the TMS pulse causes all muscle fibres involved in the contraction just prior to the onset of the silent period to relax simultaneously. This allows us to study muscle relaxation as only a property of the muscle, i.e. without voluntary influences.
In this study, the investigators will measure muscle relaxation in several myopathies (McArdle disease, Nemaline myopathy type 6 and myotonic dystrophy type 2) and compare this to healthy controls and to controls with no myopathy but with similar complaints (myalgia, stiffness, cramps). The data from these two control groups has been gathered previously in a different study. The investigators will also compare this to patients suffering from Brody disease who were previously measured in a different study.
Muscle relaxation will be evaluated in fresh and fatigued finger flexor muscles. The main outcome of this study is the peak relaxation rate normalized to the peak force preceding relaxation.
The final outlook of this research is to evaluate whether muscle relaxation studied with TMS, can be used for different myopathies as a diagnostic tool, to monitor disease progression, and to study the effects of different interventions (e.g. medication, exercise).
- Being tested
- Transcranial magnetic stimulation (TMS)
- Keywords
- muscle relaxation, transcranial magnetic stimulation, myopathy
- Medical subject headings
- Myotonic Dystrophy, Glycogen Storage Disease Type V, Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial magnetic stimulation (TMS)Diagnostic test
Single pulse, monophasic transcranial magnetic stimulation
| Study group | Role | What they receive |
|---|---|---|
| Nemaline myopathy type 6 (NEM6) | Patients diagnosed with nemaline myopathy type 6 (mutation in KBTBD13 gene). The aim is to measure five male and five female patients. Receives: Diagnostic Test: Transcranial magnetic stimulation (TMS) | |
| Myotonic dystrophy type 2 (DM2) | Patients diagnosed with myotonic dystrophy type 2 (pathological repeat expansion in CNBP gene). The aim is to measure five male and five female patients. Receives: Diagnostic Test: Transcranial magnetic stimulation (TMS) | |
| McArdle disease (McA) | Patients diagnosed with McArdle disease (mutation in PYGM gene). The aim is to measure five male and five female patients. Receives: Diagnostic Test: Transcranial magnetic stimulation (TMS) | |
| Healthy controls | 14 male and 10 female healthy subjects were measured in a previous study | |
| Controls with positive muscle phenomena | 9 male and 8 female subjects with positive muscle phenomena but no myopathy, ruled out by normal muscle biopsy, CK level, and genetic testing. These subjects were measured in a previous study. | |
| Brody disease | 4 male patients diagnosed with Brody disease (ATP2A1 mutation). All Dutch patients suffering from Brody disease (n=4) were measured in a previous study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Normalized peak relaxation rate
Maximal rate at which the muscle relaxes after the TMS pulse, defined as the steepest point on the force curve.
This value is normalised to the force that preceded relaxation, i.e. top of the superimposed twitch.
Measured: 1 hour
Secondary outcomes (3)
Force decline at 150ms
The force decline (percentage of peak force) at 150ms after TMS stimulation.
Measured: 1 hour
Relaxation times (RT)
The time needed for force to decline to a certain percentage of peak force. E.g. the 75% relaxation time, is defined as the time needed for force to decline from 100% (i.e. force before relaxation onset) to 75%.
Different relaxation times will be evaluated, e.g. 90% RT, 75% RT, and 50% RT
Measured: 1 hour
Maximal muscle strength
The highest point on the force curve prior to TMS stimulus
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2017
- Study start5 Jan 2017
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nemaline Myopathy Type 6Studies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Baziel G van Engelen, MD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03211923
- Sponsor's protocol ID
- NL57301.091.16
- Status last verified
- Sep 2018
- First submitted
- 28 Jun 2017
- Last updated
- 1 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Muscle Relaxation Properties in Myopathies With Positive Muscle Phenomena: a Study Using Transcranial Magnetic Stimulation
- ClinicalTrials.gov ID
- NCT03211923
- Acronym / sponsor ID
- NL57301.091.16
- Keywords
- muscle relaxation, transcranial magnetic stimulation, myopathy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 5 Jan 2017 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 7 Jul 2017 (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.
The aim of this study is to quantify muscle relaxation properties of the finger flexor muscles in patients with different myopathies. The inhibiting effects of transcranial magnetic stimulation (TMS) on the cortical motor hand area are used to induce relaxation, which in turn will be monitored with handgrip dynamometry and EMG. The investigators will evaluate if this technique can be implemented as a diagnostic tool in clinical practice.
Muscle relaxation is an often overlooked property of the muscle as compared to muscle strength or activation. Muscle relaxation is affected in different myopathies, such as myotonic dystrophy, non-dystrophic myotonias, and Brody myopathy. Therefore, a diagnostic tool to quantify muscle relaxation is of clinical and scientific importance. In this study, transcranial magnetic stimulation (TMS) is used, in combination with a dynamometer to quantify muscle relaxation properties.
Transcranial magnetic stimulation (TMS) is a non-invasive technique that is commonly used to stimulate the brain. In practice, a circular coil is held directly above the scalp, upon which a strong current pulse induces a magnetic field that stimulates the underlying superficial brain areas. This stimulation can have both activating and inhibiting effects.
When the motor cortex (i.e. the area of the brain that controls muscle contractions) is strongly stimulated with TMS during a voluntary muscle contraction, both excitatory and inhibitory effects can be observed in the muscle the targeted cortical area controls. The inhibitory effect entails a transient interruption of neural drive to the muscle. This interruption, called the "silent period", lasts for less than half a second and results in the relaxation of the muscle. Muscle activity and control quickly return to normal after the silent period.
The elegance and main advantage of TMS-induced muscle relaxation lies in the fact that it excludes all voluntary influences on the relaxation process. Furthermore, the TMS pulse causes all muscle fibres involved in the contraction just prior to the onset of the silent period to relax simultaneously. This allows us to study muscle relaxation as only a property of the muscle, i.e. without voluntary influences.
In this study, the investigators will measure muscle relaxation in several myopathies (McArdle disease, Nemaline myopathy type 6 and myotonic dystrophy type 2) and compare this to healthy controls and to controls with no myopathy but with similar complaints (myalgia, stiffness, cramps). The data from these two control groups has been gathered previously in a different study. The investigators will also compare this to patients suffering from Brody disease who were previously measured in a different study.
Muscle relaxation will be evaluated in fresh and fatigued finger flexor muscles. The main outcome of this study is the peak relaxation rate normalized to the peak force preceding relaxation.
The final outlook of this research is to evaluate whether muscle relaxation studied with TMS, can be used for different myopathies as a diagnostic tool, to monitor disease progression, and to study the effects of different interventions (e.g. medication, exercise).
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Nemaline myopathy type 6 (NEM6) | – | Diagnostic Test: Transcranial magnetic stimulation (TMS)Patients diagnosed with nemaline myopathy type 6 (mutation in KBTBD13 gene). The aim is to measure five male and five female patients. |
| Myotonic dystrophy type 2 (DM2) | – | Diagnostic Test: Transcranial magnetic stimulation (TMS)Patients diagnosed with myotonic dystrophy type 2 (pathological repeat expansion in CNBP gene). The aim is to measure five male and five female patients. |
| McArdle disease (McA) | – | Diagnostic Test: Transcranial magnetic stimulation (TMS)Patients diagnosed with McArdle disease (mutation in PYGM gene). The aim is to measure five male and five female patients. |
| Healthy controls | – | –14 male and 10 female healthy subjects were measured in a previous study |
| Controls with positive muscle phenomena | – | –9 male and 8 female subjects with positive muscle phenomena but no myopathy, ruled out by normal muscle biopsy, CK level, and genetic testing. These subjects were measured in a previous study. |
| Brody disease | – | –4 male patients diagnosed with Brody disease (ATP2A1 mutation). All Dutch patients suffering from Brody disease (n=4) were measured in a previous study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Diagnosis of one of the following myopathies: Nemaline myopathy type 6 (NEM6), Myotonic dystrophy type 2 (DM2), McArdle disease. Patients will be selected from a local database at the Radboud University Medical Center. The goal is to include 5 men and 5 women per myopathy.
Key inclusion criteria (1 listed)
- Diagnosis of one of the following myopathies: Nemaline myopathy type 6 (NEM6), Myotonic dystrophy type 2 (DM2), McArdle disease.
Key exclusion criteria (6 listed)
- Pregnancy
- Serious head trauma or brain surgery
- Large or ferromagnetic metal parts in the head
- Implanted cardiac pacemaker or neurostimulator
- Epilepsy, convulsion or seizure
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 |
|---|---|---|
| Transcranial magnetic stimulation (TMS)Single pulse, monophasic transcranial magnetic stimulation | Diagnostic test | McArdle disease (McA), Myotonic dystrophy type 2 (DM2), Nemaline myopathy type 6 (NEM6) |
Primary outcome
Normalized peak relaxation rate
Time frame: 1 hour
Maximal rate at which the muscle relaxes after the TMS pulse, defined as the steepest point on the force curve. This value is normalised to the force that preceded relaxation, i.e. top of the superimposed twitch.
3 secondary outcomes
Force decline at 150ms
Time frame: 1 hour
Relaxation times (RT)
Time frame: 1 hour
Maximal muscle strength
Time frame: 1 hour
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2019.
- Individual participant dataSharing planned: No
Related trials for Nemaline Myopathy Type 6
RecruitingObservational study
Natural History Study for Patients With Nemaline Myopathy in Spain
Nemaline Myopathy, Myopathies
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 G van Engelen, MD, PhD principal investigator
Radboud University Medical Center
Questions about this trial
What is this clinical trial studying?
An observational study of Nemaline Myopathy Type 6 and Myotonic Dystrophy Type 2, run by Radboud University Medical Center.
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 1 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 1 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Results are not available in the source record.
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?
Normalized peak relaxation rate (time frame: 1 hour). 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 1 Oct 2019.