Recessive Gene MyopathiesCICSNCT02897921
Clinical Importance of Carrier Status of Recessive Gene Mutations in Myopathy (CICS)
An observational study of Recessive Gene Myopathies, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
Many myopathies are inherited in a recessive manner, but in some of these recessively inherited disorders, clinical manifestations may potentially manifest in carriers of just a single mutation. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Recessive Gene Myopathies
- How many people
- 240 participants
- Where
- 1 siteDenmark
- Study dates
- Oct 2016to Aug 2021
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: 2 groups are studied: 1) Single mutation carriers of recessive myopathies. 2) Healthy controls.
Who may be able to join
- Verified carrier status of recessive myopathy mutation before entry into the study
- Age of 18 years or older
- Age of 18 years or older
Who cannot join
- Contraindications for MRI (pacemaker or other internal metal or magnetic devices)
- Claustrophobia
- Pregnancy at the time of MRI
- After investigators judgement
- Healthy controls:
- Contraindications for MRI (pacemaker or other internal metal or magnetic devices)
Show all 9Show fewer
- Claustrophobia
- Pregnancy at the time of MRI
- After investigators judgement
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Copenhagen Neuromuscular Center, Rigshospitalet, 3342
Copenhagen, DK-2100
About this study
Official title: Clinical Importance of Carrier Status of Recessive Gene Mutations in Myopathy
Many myopathies are inherited in a recessive manner, but in some of these recessively inherited disorders, clinical manifestations may potentially manifest in carriers of just a single mutation.
The aim of the study is to describe the clinical characteristics of single mutation carriers of recessive myopathy, through measuring serum creatine kinase, muscle strength, muscle degeneration (by MRI) and heart affection. The investigators will do this by blood sampling, Biodex 4 Isokinetic Dynamometer, MRI analysis, ECG, Holter monitoring, and echocardiography.
The aim is further to describe whether these characteristics are found primarily with specific mutations.
Read the detailed description
Background:
Many myopathies are inherited in a recessive manner, but in some of these recessively inherited disorders, clinical manifestations may potentially manifest in carriers of just a single mutation. This has recently been demonstrated by researchers for the recessively inherited limb girdle muscle dystrophy (LGMD) type 2A, where carriers of single mutations can also be symptomatic. In X-linked recessively inherited dystrophinopathies caused by mutations in the DMD gene on chromosome Xp21, female mutation carriers may also manifest with disease, although this is often milder than affected men. In the recently discovered LGMD2L, manifesting carriers are also suspected. Thus, according to statistics, too many persons evaluated for myopathy carry a single LGMD2L mutation.
Some previous studies have looked into the significance of being a single mutation carrier in recessive muscle disease. In dystrophinopathy, it was reported that 5 % of female DMD carriers reported myalgia and cramps, 17 % experienced mild-to-moderate muscle weakness and 8 % experienced dilated cardiomyopathy, with a mean onset age of approximately 30 years. Another study found that echocardiographic examination was abnormal in up to 38% of DMD female carriers - some with dilated cardiomyopathy, and some with left ventricle dilatation.
Overall, however significance of carrying a single mutation of recessive myopathy is widely unexplored. No study has yet investigated the characteristics of single mutation carriers of recessive myopathy in an observational, cross-sectional study.
Aim:
In this study, clinical characteristics of single mutation carriers of recessive myopathies will be investigated. The investigation will include sceletal muscle degeneration and strength, as well as cardiac status.
Recruitment and Methods:
Estimated total of subjects recruited is 200 with known recessive gene mutations, and 40 healthy controls. In former studies 40 healthy volunteers have already been investigated, thereby giving a total of 80 healthy controls. Recessive gene carrier recruits will be obtained via the Department of Clinical Genetics and Copenhagen Neuromuscular Center, Rigshospitalet, thus only including carriers aware of their carrier status.
2 days of testing per participant. Day one: Measuring S-creatine kinase level (blood sampling), muscle strength (Biodex 4 Isokinetic Dynamometer), ECG, and Holter monitor device application.
Day two: Holter monitor device removal, Dixon MRI analysis with gadolinium contrast medium, and echocardiography.
Healthy controls will take part in MRI-scanning and isokinetic dynamometer testing.
Trials are expected to be carried out between October 2016 and May 2020.
- Conditions
- Recessive Gene Myopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Carriers of recessive gene mutations of myopathies | Patients with several different kinds of recessively inherited myopathy genes, such as for example Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, Limb Girdle limb girdle muscle dystrophy (LGMD) type 2A and 2L etc. Investigated by blood sampling, Biodex 4 Isokinetic Dynamometer, MRI analysis, ECG, Holter monitoring, and echocardiography. | |
| Healthy controls | Healthy controls, investigated by blood sampling, Biodex 4 Isokinetic Dynamometer and MRI analysis. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac status
We will use MRI with a contrast agent (gadolinium). Kidney function and contrast allergy status will be tested prior to use of contrast agent, and avoided if the participant is not suitable for contrast injection.
Measured: MRI of cardiac status and muscles takes around 1,5 hours
Muscle tissue quality
Muscle tissue cross sectional area and fat percent will be investigated and measured by Dixon MRI scan.
Measured: MRI of cardiac status and muscles takes around 1,5 hours
Secondary outcomes (4)
Serum CK-levels
Blood sampling
Measured: Estimated time 5 minutes.
Muscle strength
Investigated by an isokinetic dynamometer (Biodex 4).
Measured: Testing takes around 10-20 minutes
ECG
ECG electrodes will be places on the subject's chest, and an electrocardigram will be measured.
Measured: Estimated time: 5 minutes.
Holter monitor
The electrodes will be places on the chest and the monitor attached in a line around the neck. 24-48 hours of electrocardiogram will be measured.
Measured: A Holter monitor device will be attached on test day 1, and worn until test day 2 (24-48 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2016 (estimated)
- Study startOct 2016
- Primary completionMay 2020 (estimated)
- Study completionAug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Recessive Gene MyopathiesStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe 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
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tove Freja Maria Fornander, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Tove Freja M Fornander, B. Sc., Principal investigator, Copenhagen Neuromuscular Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02897921
- Sponsor's protocol ID
- H-16035677
- Acronym
- CICS
- Status last verified
- May 2018
- First submitted
- 7 Sep 2016
- Last updated
- 21 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: No plan
Publications
Hoogerwaard EM, van der Wouw PA, Wilde AA, Bakker E, Ippel PF, Oosterwijk JC, Majoor-Krakauer DF, van Essen AJ, Leschot NJ, de Visser M. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 1999 Jul;9(5):347-51. doi: 10.1016/s0960-8966(99)00018-8.
PubMed 10407858Lee SH, Lee JH, Lee KA, Choi YC. Clinical and Genetic Characterization of Female Dystrophinopathy. J Clin Neurol. 2015 Jul;11(3):248-51. doi: 10.3988/jcn.2015.11.3.248. Epub 2015 May 28.
PubMed 26022459Vissing J, Barresi R, Witting N, Van Ghelue M, Gammelgaard L, Bindoff LA, Straub V, Lochmuller H, Hudson J, Wahl CM, Arnardottir S, Dahlbom K, Jonsrud C, Duno M. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy. Brain. 2016 Aug;139(Pt 8):2154-63. doi: 10.1093/brain/aww133. Epub 2016 Jun 3.
PubMed 27259757Flanigan KM. Oxford Textbook of Neuromuscular Disorders chapter 22 "The dystrophinopathies". Oxford University Press 2014, first edition.
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Importance of Carrier Status of Recessive Gene Mutations in Myopathy
- ClinicalTrials.gov ID
- NCT02897921
- Acronym / sponsor ID
- CICS / H-16035677
- Conditions
- Recessive Gene Myopathies
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- Oct 2016
- Primary completion
- May 2020 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 13 Sep 2016 (estimated)
- 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.
Many myopathies are inherited in a recessive manner, but in some of these recessively inherited disorders, clinical manifestations may potentially manifest in carriers of just a single mutation.
The aim of the study is to describe the clinical characteristics of single mutation carriers of recessive myopathy, through measuring serum creatine kinase, muscle strength, muscle degeneration (by MRI) and heart affection. The investigators will do this by blood sampling, Biodex 4 Isokinetic Dynamometer, MRI analysis, ECG, Holter monitoring, and echocardiography.
The aim is further to describe whether these characteristics are found primarily with specific mutations.
Detailed description
Background:
Many myopathies are inherited in a recessive manner, but in some of these recessively inherited disorders, clinical manifestations may potentially manifest in carriers of just a single mutation. This has recently been demonstrated by researchers for the recessively inherited limb girdle muscle dystrophy (LGMD) type 2A, where carriers of single mutations can also be symptomatic. In X-linked recessively inherited dystrophinopathies caused by mutations in the DMD gene on chromosome Xp21, female mutation carriers may also manifest with disease, although this is often milder than affected men. In the recently discovered LGMD2L, manifesting carriers are also suspected. Thus, according to statistics, too many persons evaluated for myopathy carry a single LGMD2L mutation.
Some previous studies have looked into the significance of being a single mutation carrier in recessive muscle disease. In dystrophinopathy, it was reported that 5 % of female DMD carriers reported myalgia and cramps, 17 % experienced mild-to-moderate muscle weakness and 8 % experienced dilated cardiomyopathy, with a mean onset age of approximately 30 years. Another study found that echocardiographic examination was abnormal in up to 38% of DMD female carriers - some with dilated cardiomyopathy, and some with left ventricle dilatation.
Overall, however significance of carrying a single mutation of recessive myopathy is widely unexplored. No study has yet investigated the characteristics of single mutation carriers of recessive myopathy in an observational, cross-sectional study.
Aim:
In this study, clinical characteristics of single mutation carriers of recessive myopathies will be investigated. The investigation will include sceletal muscle degeneration and strength, as well as cardiac status.
Recruitment and Methods:
Estimated total of subjects recruited is 200 with known recessive gene mutations, and 40 healthy controls. In former studies 40 healthy volunteers have already been investigated, thereby giving a total of 80 healthy controls. Recessive gene carrier recruits will be obtained via the Department of Clinical Genetics and Copenhagen Neuromuscular Center, Rigshospitalet, thus only including carriers aware of their carrier status.
2 days of testing per participant. Day one: Measuring S-creatine kinase level (blood sampling), muscle strength (Biodex 4 Isokinetic Dynamometer), ECG, and Holter monitor device application.
Day two: Holter monitor device removal, Dixon MRI analysis with gadolinium contrast medium, and echocardiography.
Healthy controls will take part in MRI-scanning and isokinetic dynamometer testing.
Trials are expected to be carried out between October 2016 and May 2020.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carriers of recessive gene mutations of myopathies | – | –Patients with several different kinds of recessively inherited myopathy genes, such as for example Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, Limb Girdle limb girdle muscle dystrophy (LGMD) type 2A and 2L etc. Investigated by blood sampling, Biodex 4 Isokinetic Dynamometer, MRI analysis, ECG, Holter monitoring, and echocardiography. |
| Healthy controls | – | –Healthy controls, investigated by blood sampling, Biodex 4 Isokinetic Dynamometer and MRI analysis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 2 groups are studied: 1) Single mutation carriers of recessive myopathies. 2) Healthy controls.
Key inclusion criteria (3 listed)
- Verified carrier status of recessive myopathy mutation before entry into the study
- Age of 18 years or older
- Age of 18 years or older
Key exclusion criteria (9 listed)
- Contraindications for MRI (pacemaker or other internal metal or magnetic devices)
- Claustrophobia
- Pregnancy at the time of MRI
- After investigators judgement
- Contraindications for MRI (pacemaker or other internal metal or magnetic devices)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cardiac status
Time frame: MRI of cardiac status and muscles takes around 1,5 hours
We will use MRI with a contrast agent (gadolinium). Kidney function and contrast allergy status will be tested prior to use of contrast agent, and avoided if the participant is not suitable for contrast injection.
Muscle tissue quality
Time frame: MRI of cardiac status and muscles takes around 1,5 hours
Muscle tissue cross sectional area and fat percent will be investigated and measured by Dixon MRI scan.
4 secondary outcomes
Serum CK-levels
Time frame: Estimated time 5 minutes.
Muscle strength
Time frame: Testing takes around 10-20 minutes
ECG
Time frame: Estimated time: 5 minutes.
Holter monitor
Time frame: A Holter monitor device will be attached on test day 1, and worn until test day 2 (24-48 hours)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2018.
- Background: PubMed 10407858Hoogerwaard EM, van der Wouw PA, Wilde AA, Bakker E, Ippel PF, Oosterwijk JC, Majoor-Krakauer DF, van Essen AJ, Leschot NJ, de Visser M. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 1999 Jul;9(5):347-51. doi: 10.1016/s0960-8966(99)00018-8.
- Background: PubMed 26022459Lee SH, Lee JH, Lee KA, Choi YC. Clinical and Genetic Characterization of Female Dystrophinopathy. J Clin Neurol. 2015 Jul;11(3):248-51. doi: 10.3988/jcn.2015.11.3.248. Epub 2015 May 28.
- Background: PubMed 27259757Vissing J, Barresi R, Witting N, Van Ghelue M, Gammelgaard L, Bindoff LA, Straub V, Lochmuller H, Hudson J, Wahl CM, Arnardottir S, Dahlbom K, Jonsrud C, Duno M. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy. Brain. 2016 Aug;139(Pt 8):2154-63. doi: 10.1093/brain/aww133. Epub 2016 Jun 3.
- BackgroundFlanigan KM. Oxford Textbook of Neuromuscular Disorders chapter 22 "The dystrophinopathies". Oxford University Press 2014, first edition.
- Individual participant dataSharing planned: No. No plan
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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.
Tove Freja M Fornander, B. Sc. principal investigator
Copenhagen Neuromuscular Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Recessive Gene Myopathies, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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 9 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 21 May 2018. 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 Denmark. 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. 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?
Cardiac status (time frame: MRI of cardiac status and muscles takes around 1,5 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02897921, which also lists 4 linked publications.
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 21 May 2018.