Myotubular MyopathyNCT01817946
Myotubular Myopathy Genetic Testing Study
An observational study of Myotubular Myopathy, run by Cure CMD at 1 site in United States.
Trial summary
Myotubular myopathy (XLMTM) is an X-linked disorder caused by mutations in the myotubularin gene (MTM1). The clinical spectrum is variable and ranges from individuals who require a wheelchair and full time breathing support to those who are able to walk and breathe on their own. Read more about this study
- Who is it for?
- Ages 30 days and older
- Conditions the study is for
- Myotubular Myopathy
- What is being tested?
- Genetic Testing
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Mar 2017
- 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 30 days and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study will be composed of individuals registered in the CMDIR who have been clinically diagnosed with XLMTM but do not have an XLMTM diagnosis confirmed by genetic testing.
Who may be able to join
None listed.
Who cannot join
- 1. Carrier testing for asymptomatic mothers.
Trial locations and contacts
1 site in 1 country.
United States1 site
Congenital Muscle Disease International Registry
Torrance, California, 90502
About this study
Myotubular myopathy (XLMTM) is an X-linked disorder caused by mutations in the myotubularin gene (MTM1). The clinical spectrum is variable and ranges from individuals who require a wheelchair and full time breathing support to those who are able to walk and breathe on their own. Symptoms of myotubular myopathy include long faces, facial weakness with eye muscle weakness, breathing support with a muscle biopsy demonstrating central nucleated fibers. These symptoms may be caused by mutations or changes in the MTM1, BIN1 (bridging integrator 1), DNM2 (dynamin 2) and RYR1 (ryanodine receptor 1) genes. However, the majority are caused by mutations in the MTM1 gene. Some patients with symptoms consistent with myotubular myopathy who initially have negative testing of the MTM1 gene were later found to have a unique type of change in the MTM1 gene. This unique change, called a deletion or duplication, can be found with a different type of genetic test called a CGH (comparative genomic hybridization) array.
Investigators do not know how frequent deletions and duplications are in patients with X-linked myotubular myopathy. Recently, there have been advances in identifying potential treatments for XLMTM. The next step will be to proceed with clinical trials of potential treatments. In order to be ready for clinical trials, it is important that investigators find the specific genetic change that is causing XLMTM in people with this diagnosis. This study will attempt to find changes in the MTM1 gene in individuals who have clinical symptoms consistent with a diagnosis of XLMTM. Participants will be asked to enroll in the CMDIR (Congenital Muscle Disease International Registry), complete a brief clinical survey, provide access to medical records, and provide a saliva or blood sample for genetic testing. Results of genetic testing will be communicated to participants by the physician specified in the consent by the signing person.
Read more
Study Hypothesis:
Not all individuals with a clinical diagnosis of XLMTM have access to genetic testing. Investigators know that deletions and duplications of the MTM1 gene can cause XLMTM. Investigators will find more individuals with XLMTM by performing genetic testing of the MTM1 gene, including CGH array for deletions and duplications.
Read the detailed description
- Prospective participants will complete registration in the CMDIR.
- The CMDIR genetic curator will review CMDIR data for study eligibility.
- If eligible, participant will be called and consented to participate in the study.
- Sequencing can be done with a saliva sample. However, if this method does not detect a mutation or change in the MTM1 gene, a further test, called CGH Array, has to be performed. For the CGH Array test, a saliva sample may deliver a clear result in terms of a deletion/duplication mutation. In the event, CGH Array with the saliva sample does not provide a result, a the blood sample is necessary to repeat CGH Array.
- The study participant will receive a kit and instructions for saliva specimen collection for genetic testing from the CMDIR in the mail.
- If a mutation or change in the MTM1 gene could not be found by genetic testing and CGH Array with a saliva sample, the study participant will receive a second kit in the mail from the CMDIR with instructions for a blood draw to be used for CGH Array.
- The family will coordinate collection of the saliva specimen or a local blood draw, if necessary, and will be responsible for mailing the specimen in a pre-paid parcel to the University of Chicago. There will be a $40 reimbursement for the cost of the blood draw. Mailing the specimen to the testing site is at no cost for the participant. A two-week turn-around from receipt of the kit to sending it to the testing laboratory is requested.
- Genetic testing will start with standard sequencing of the MTM1 gene, isolated from the saliva specimen, followed by CGH Array if sequencing of the MTM1 gene isolated from the saliva sample or further from a blood sample if a variant consistent with the symptoms could not be detected using the saliva sample.
- Test results will be 1) reported to a physician specified by the study participant and 2) uploaded into the study participant's profile in the CMDIR and 3) if concurrently enrolled in the Beggs Laboratory or other IRB-approved clinical study, test results will also be made available to that study provided appropriate informed consent has been given.
- Conditions
- Myotubular Myopathy
- Being tested
- Genetic Testing
- Keywords
- Congenital Myopathy, Centronuclear Myopathy, Myotubular Myopathy, Myotubularin, MTM1 Gene, Genetic testing, Sequencing, Deletion/Duplication Mutation, CGH array
- Medical subject headings
- Myopathies, Structural, Congenital, Myotonia Congenita
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic TestingOther
Also called Sequencing
Genetic testing services will be provided by the University of Chicago under the guidance of Dr. Soma Das, PhD. Services will be coordinated by Rachel Alvarez, CMDIR Associate Director. Genetic testing will include standard sequencing of the MTM1 gene followed by CGH array for deletion/duplication in cases where no pathologic variant is identified by standard sequencing.
| Study group | Role | What they receive |
|---|---|---|
| Genetic testing | All participants determined eligible for the study will be placed into genetic testing arm. Receives: Other: Genetic Testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Description of Mutations in the MTM1 Gene by Complete Genetic Sequencing
To confirm presence, locations and frequencies of mutations in the MTM1 gene in study participants presenting with symptoms as listed in the Brief Summary and muscle biopsy and/or family history typical for myotubular myopathy or prior confirmation of a mutation in the MTM1 gene by research sequencing.
Measured: 1 year
Secondary outcomes (2)
Frequency of Deletion/Duplication Mutations in the MTM1 Gene by CGH Array Testing
To establish the frequency of deletions/duplications in the MTM1 gene for patients who have negative sequencing but have clinical history/muscle biopsy/family history.
Measured: 1 year
To Examine the Relation of the Mutation in the MTM1 Gene to the Phenotype
Investigators will compare mutations characterized by sequencing and CGH array (if necessary) with the following data in the study participant's CMDIR profile: age of onset, ventilatory support needed post-natal and ongoing, maximal motor function achieved, current motor function, need for gastrostomy tube and rate of ER visits and hospitalizations. The individual genotype - phenotype relation will then be compared to that of other study participants. In the event that a genotype-phenotype pattern can be established, this may help predict the course of the disease and prepare for appropriate care.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2013 (estimated)
- Study startMar 2013
- Primary completionMar 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Myotubular MyopathyStudies of the same condition, open and under way.
- 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 only
- Time perspective
- Cross-sectional
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cure CMD
- Sponsor type
- University, hospital or other
- Collaborators
- Valerion Therapeutics, LLC, Congenital Muscle Disease International Registr, University of Chicago, Boston Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Sabine de Chastonay, PhD, Principal investigator, CMDIRElizabeth DeChene, MS, GCG, Principal investigator, Children's Hospital of PhiladelphiaSoma Das, PhD, Principal investigator, University of Chicago Genetic Testing Services Laboratory
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01817946
- Sponsor's protocol ID
- CMDIR-001
- Status last verified
- Mar 2018
- First submitted
- 19 Mar 2013
- Last updated
- 7 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Trump N, Cullup T, Verheij JB, Manzur A, Muntoni F, Abbs S, Jungbluth H. X-linked myotubular myopathy due to a complex rearrangement involving a duplication of MTM1 exon 10. Neuromuscul Disord. 2012 May;22(5):384-8. doi: 10.1016/j.nmd.2011.11.004. Epub 2011 Dec 9.
PubMed 22153990Oliveira J, Oliveira ME, Kress W, Taipa R, Pires MM, Hilbert P, Baxter P, Santos M, Buermans H, den Dunnen JT, Santos R. Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database. Eur J Hum Genet. 2013 May;21(5):540-9. doi: 10.1038/ejhg.2012.201. Epub 2012 Sep 12.
PubMed 22968136Bevilacqua JA, Bitoun M, Biancalana V, Oldfors A, Stoltenburg G, Claeys KG, Lacene E, Brochier G, Manere L, Laforet P, Eymard B, Guicheney P, Fardeau M, Romero NB. "Necklace" fibers, a new histological marker of late-onset MTM1-related centronuclear myopathy. Acta Neuropathol. 2009 Mar;117(3):283-91. doi: 10.1007/s00401-008-0472-1. Epub 2008 Dec 16.
PubMed 19084976Gurgel-Giannetti J, Zanoteli E, de Castro Concentino EL, Abath Neto O, Pesquero JB, Reed UC, Vainzof M. Necklace fibers as histopathological marker in a patient with severe form of X-linked myotubular myopathy. Neuromuscul Disord. 2012 Jun;22(6):541-5. doi: 10.1016/j.nmd.2011.12.005. Epub 2012 Jan 20.
PubMed 22264517North KN. Clinical approach to the diagnosis of congenital myopathies. Semin Pediatr Neurol. 2011 Dec;18(4):216-20. doi: 10.1016/j.spen.2011.10.002.
PubMed 22172416Dowling JJ, Lawlor MW, Das S. X-Linked Myotubular Myopathy. 2002 Feb 25 [updated 2018 Aug 23]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1432/
PubMed 20301605Tosch V, Vasli N, Kretz C, Nicot AS, Gasnier C, Dondaine N, Oriot D, Barth M, Puissant H, Romero NB, Bonnemann CG, Heller B, Duval G, Biancalana V, Laporte J. Novel molecular diagnostic approaches for X-linked centronuclear (myotubular) myopathy reveal intronic mutations. Neuromuscul Disord. 2010 Jun;20(6):375-81. doi: 10.1016/j.nmd.2010.03.015.
PubMed 20434914
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Myotubular Myopathy Genetic Testing Study
- ClinicalTrials.gov ID
- NCT01817946
- Acronym / sponsor ID
- CMDIR-001
- Conditions
- Myotubular Myopathy
- Keywords
- Congenital Myopathy, Centronuclear Myopathy, Myotubular Myopathy, Myotubularin, MTM1 Gene, Genetic testing, Sequencing, Deletion/Duplication Mutation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Cure CMDUniversity, hospital or other
- Collaborators
- Valerion Therapeutics, LLC, Congenital Muscle Disease International Registr, University of Chicago, Boston Children's Hospital
- Study start
- Mar 2013 (actual)
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 26 Mar 2013 (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.
Myotubular myopathy (XLMTM) is an X-linked disorder caused by mutations in the myotubularin gene (MTM1). The clinical spectrum is variable and ranges from individuals who require a wheelchair and full time breathing support to those who are able to walk and breathe on their own. Symptoms of myotubular myopathy include long faces, facial weakness with eye muscle weakness, breathing support with a muscle biopsy demonstrating central nucleated fibers. These symptoms may be caused by mutations or changes in the MTM1, BIN1 (bridging integrator 1), DNM2 (dynamin 2) and RYR1 (ryanodine receptor 1) genes. However, the majority are caused by mutations in the MTM1 gene. Some patients with symptoms consistent with myotubular myopathy who initially have negative testing of the MTM1 gene were later found to have a unique type of change in the MTM1 gene. This unique change, called a deletion or duplication, can be found with a different type of genetic test called a CGH (comparative genomic hybridization) array.
Investigators do not know how frequent deletions and duplications are in patients with X-linked myotubular myopathy. Recently, there have been advances in identifying potential treatments for XLMTM. The next step will be to proceed with clinical trials of potential treatments. In order to be ready for clinical trials, it is important that investigators find the specific genetic change that is causing XLMTM in people with this diagnosis. This study will attempt to find changes in the MTM1 gene in individuals who have clinical symptoms consistent with a diagnosis of XLMTM. Participants will be asked to enroll in the CMDIR (Congenital Muscle Disease International Registry), complete a brief clinical survey, provide access to medical records, and provide a saliva or blood sample for genetic testing. Results of genetic testing will be communicated to participants by the physician specified in the consent by the signing person.
Study Hypothesis:
Not all individuals with a clinical diagnosis of XLMTM have access to genetic testing. Investigators know that deletions and duplications of the MTM1 gene can cause XLMTM. Investigators will find more individuals with XLMTM by performing genetic testing of the MTM1 gene, including CGH array for deletions and duplications.
Detailed description
- Prospective participants will complete registration in the CMDIR.
- The CMDIR genetic curator will review CMDIR data for study eligibility.
- If eligible, participant will be called and consented to participate in the study.
- Sequencing can be done with a saliva sample. However, if this method does not detect a mutation or change in the MTM1 gene, a further test, called CGH Array, has to be performed. For the CGH Array test, a saliva sample may deliver a clear result in terms of a deletion/duplication mutation. In the event, CGH Array with the saliva sample does not provide a result, a the blood sample is necessary to repeat CGH Array.
- The study participant will receive a kit and instructions for saliva specimen collection for genetic testing from the CMDIR in the mail.
- If a mutation or change in the MTM1 gene could not be found by genetic testing and CGH Array with a saliva sample, the study participant will receive a second kit in the mail from the CMDIR with instructions for a blood draw to be used for CGH Array.
- The family will coordinate collection of the saliva specimen or a local blood draw, if necessary, and will be responsible for mailing the specimen in a pre-paid parcel to the University of Chicago. There will be a $40 reimbursement for the cost of the blood draw. Mailing the specimen to the testing site is at no cost for the participant. A two-week turn-around from receipt of the kit to sending it to the testing laboratory is requested.
- Genetic testing will start with standard sequencing of the MTM1 gene, isolated from the saliva specimen, followed by CGH Array if sequencing of the MTM1 gene isolated from the saliva sample or further from a blood sample if a variant consistent with the symptoms could not be detected using the saliva sample.
- Test results will be 1) reported to a physician specified by the study participant and 2) uploaded into the study participant's profile in the CMDIR and 3) if concurrently enrolled in the Beggs Laboratory or other IRB-approved clinical study, test results will also be made available to that study provided appropriate informed consent has been given.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Genetic testing | – | Other: Genetic TestingAll participants determined eligible for the study will be placed into genetic testing arm. |
Who may qualify
- Ages
- 30 days and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study will be composed of individuals registered in the CMDIR who have been clinically diagnosed with XLMTM but do not have an XLMTM diagnosis confirmed by genetic testing.
Key inclusion criteria (0 listed)
Key exclusion criteria (1 listed)
- 1. Carrier testing for asymptomatic mothers.
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 |
|---|---|---|
| Genetic TestingAlso: SequencingGenetic testing services will be provided by the University of Chicago under the guidance of Dr. Soma Das, PhD. Services will be coordinated by Rachel Alvarez, CMDIR Associate Director. Genetic testing will include standard sequencing of the MTM1 gene followed by CGH array for deletion/duplication in cases where no pathologic variant is identified by standard sequencing. | Other | Genetic testing |
Primary outcome
Description of Mutations in the MTM1 Gene by Complete Genetic Sequencing
Time frame: 1 year
To confirm presence, locations and frequencies of mutations in the MTM1 gene in study participants presenting with symptoms as listed in the Brief Summary and muscle biopsy and/or family history typical for myotubular myopathy or prior confirmation of a mutation in the MTM1 gene by research sequencing.
2 secondary outcomes
Frequency of Deletion/Duplication Mutations in the MTM1 Gene by CGH Array Testing
Time frame: 1 year
To Examine the Relation of the Mutation in the MTM1 Gene to the Phenotype
Time frame: 2 years
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 7 Mar 2018.
- Background: PubMed 22153990Trump N, Cullup T, Verheij JB, Manzur A, Muntoni F, Abbs S, Jungbluth H. X-linked myotubular myopathy due to a complex rearrangement involving a duplication of MTM1 exon 10. Neuromuscul Disord. 2012 May;22(5):384-8. doi: 10.1016/j.nmd.2011.11.004. Epub 2011 Dec 9.
- Background: PubMed 22968136Oliveira J, Oliveira ME, Kress W, Taipa R, Pires MM, Hilbert P, Baxter P, Santos M, Buermans H, den Dunnen JT, Santos R. Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database. Eur J Hum Genet. 2013 May;21(5):540-9. doi: 10.1038/ejhg.2012.201. Epub 2012 Sep 12.
- Background: PubMed 19084976Bevilacqua JA, Bitoun M, Biancalana V, Oldfors A, Stoltenburg G, Claeys KG, Lacene E, Brochier G, Manere L, Laforet P, Eymard B, Guicheney P, Fardeau M, Romero NB. "Necklace" fibers, a new histological marker of late-onset MTM1-related centronuclear myopathy. Acta Neuropathol. 2009 Mar;117(3):283-91. doi: 10.1007/s00401-008-0472-1. Epub 2008 Dec 16.
- Background: PubMed 22264517Gurgel-Giannetti J, Zanoteli E, de Castro Concentino EL, Abath Neto O, Pesquero JB, Reed UC, Vainzof M. Necklace fibers as histopathological marker in a patient with severe form of X-linked myotubular myopathy. Neuromuscul Disord. 2012 Jun;22(6):541-5. doi: 10.1016/j.nmd.2011.12.005. Epub 2012 Jan 20.
- Background: PubMed 22172416North KN. Clinical approach to the diagnosis of congenital myopathies. Semin Pediatr Neurol. 2011 Dec;18(4):216-20. doi: 10.1016/j.spen.2011.10.002.
- Background: PubMed 20301605Dowling JJ, Lawlor MW, Das S. X-Linked Myotubular Myopathy. 2002 Feb 25 [updated 2018 Aug 23]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1432/
- Results publication: PubMed 20434914Tosch V, Vasli N, Kretz C, Nicot AS, Gasnier C, Dondaine N, Oriot D, Barth M, Puissant H, Romero NB, Bonnemann CG, Heller B, Duval G, Biancalana V, Laporte J. Novel molecular diagnostic approaches for X-linked centronuclear (myotubular) myopathy reveal intronic mutations. Neuromuscul Disord. 2010 Jun;20(6):375-81. doi: 10.1016/j.nmd.2010.03.015.
- Congenital Muscle Disease International RegistryLink provided by the sponsor.
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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.
Sabine de Chastonay, PhD principal investigator
CMDIR
Elizabeth DeChene, MS, GCG principal investigator
Children's Hospital of Philadelphia
Soma Das, PhD principal investigator
University of Chicago Genetic Testing Services Laboratory
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 Myotubular Myopathy, run by Cure CMD at 1 site in United States.
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 0 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 7 Mar 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 United States. 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?
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?
Description of Mutations in the MTM1 Gene by Complete Genetic Sequencing (time frame: 1 year). 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 NCT01817946, which also lists 7 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 7 Mar 2018.