Limb Girdle Muscular DystrophyANO5 MRINCT05102799
MRI-phenotyping of Patients With Pathogenic Anoctamin 5 Variants
An observational study of Limb Girdle Muscular Dystrophy, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
A large cohort of MRI scans from patients with pathogenic variants in the anoctamin 5 gene will be collected through an international collaboration to better describe muscle involvement. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Limb Girdle Muscular Dystrophy
- How many people
- 200 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Apr 2021to 1 Aug 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: MRIs of patients with pathogenic variants in the anoctamin 5 gene will be examined. The MRIs are obtained from either former studies or as part of clinical evaluation in the collaborating countries.
Who may be able to join
- Two pathogenic variants in the anoctamin-5 gene
- T1-weighted MR-images of lower back and leg muscles.
Who cannot join
- Concomitant other disorders that also can result in muscular atrophy, i.e. polyneuropathy, other muscle diseases, recent long-term stay in intensive care, among others.
Trial locations and contacts
1 site in 1 country.
About this study
A large cohort of MRI scans from patients with pathogenic variants in the anoctamin 5 gene will be collected through an international collaboration to better describe muscle involvement.
Read the detailed description
Background:
The anoctamin 5 gene (ANO5) encodes the anoctamine 5 protein that act as a calcium-sensitive chloride channel. The protein is preferentially expressed in skeletal and cardiac muscle and bone and likely acts in the repair of the cell membrane. Pathogenic ANO5 variants inherited in a autosomal recessive trait give rise to three main phenotypes: Limb-girdle muscular dystrophy type R12 (LGMDR12, formerly classified as LGMD2L), Miyoshi distal muscular dystrophy type 3 (MMD3), and asymptomatic hyperCKemia). As the name implies, patients with LGMDR12 are affected more proximally and patients with MMD3 more distally, but the definition and distinction between the two entities is unclear. Men with anoctaminopathy are more severely affected than women. Cardiac disease such as arrhythmias and cardiomyopathy as well as bulbar symptoms or respiratory failure are very rare in anoctaminopathies. Onset is in adulthood and disease progression is slow, generally with a later onset and disease progression than seen in other LGMDs. Ambulation is preserved until late in the disease course.
However, only few studies based on small case series have investigated the phenotype of patients with ANO5 mutations using MRI. There is therefore a need to investigate a larger international group of patients using MRI to properly describe which muscles are affected in men and women with anoctaminopathy.
The spectrum of phenotypes in anoctaminopathies resembles that seen in dysferlinopathies, and in the latter group, it has been shown that the former division into LGMDR2 (formally LGMD2B) and Miyoshi distal muscular dystrophy type 2 (MMD2) is rather arbitrary. Our hypothesis is that this may very well also be the case for LGMDR12 and MMD3. A large MRI study would be able to shed light on this question. Muscle involvement in patients with ANO5 mutations is said to be asymmetric based on clinical assessments (7,8,10). The proposed study will also elucidate this by studying symmetry of muscle affection. Finally, the diseases severity is said to be marked between the two sexes, but this has not been quantified in any detail before. The proposed study will also be able to shed light on this.
Aim:
The aims of the project are:
- To describe the muscle MRI phenotype in around 200 patients from multiple countries around the world.
- To investigate if it makes sense to group patients with pathogenic ANO5 variants into proximal and distal myopathies.
- To investigate to what extent the disease is asymmetric.
- To investigate the difference in disease severity between sexes.
- To investigate whether a phenotype-genotype correlation exists.
Methods:
Sites from all over the world will share an eCRF and their MRI data with Copenhagen Neuromuscular Center through the platform MyoShare.
- Conditions
- Limb Girdle Muscular Dystrophy
- Being tested
- No intervention
- Keywords
- Anoctaminophathies
- Medical subject headings
- Muscular Dystrophies, Limb-Girdle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| Anoctaminopathies | Anoctaminopathies including Limb Girdle Muscular Dystrophy R12, Miyoshi distal Muscular Dystrophy type 3 and asymptomatic hyperCKemia Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Qualitative fat fraction lower back and legs
Qualitative muscle fat fraction analyses of lower back and legs evaluated from T1-weighted images using the Mercury score (score: 0-4)
Measured: 15 minutes
Secondary outcomes (3)
Qualitative fat fraction of whole body
Qualitative fat fraction analyses of the rest of the body evaluated from T1-weighted images using the Mercury score (score: 0-4)
Measured: 15 minutes
Quantitative fat fraction of axial and leg muscles
Qualitative fat fraction analyses of axial and leg muscles evaluated from Dixon images
Measured: 60 minutes
Inflammatory evaluation of axial and leg muscles
Quantitative analysis of inflammation in axial and leg muscles from STIR images
Measured: 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2021
- Study start1 Apr 2021
- Primary completion1 Jun 2026
- Study completion1 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Limb Girdle Muscular DystrophyStudies 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
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nanna Scharff Poulsen, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05102799
- Sponsor's protocol ID
- 1928485
- Acronym
- ANO5 MRI
- Status last verified
- Aug 2026
- First submitted
- 20 Oct 2021
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Little AA, McKeever PE, Gruis KL. Novel mutations in the Anoctamin 5 gene (ANO5) associated with limb-girdle muscular dystrophy 2L. Muscle Nerve. 2013 Feb;47(2):287-91. doi: 10.1002/mus.23542. Epub 2012 Nov 21.
PubMed 23169617Witting N, Duno M, Petri H, Krag T, Bundgaard H, Kober L, Vissing J. Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression. J Neurol. 2013 Aug;260(8):2084-93. doi: 10.1007/s00415-013-6934-y. Epub 2013 May 14.
PubMed 23670307Palmio J, Penttila S, Jokela M. ANO5-Related Muscle Disease. 2012 Nov 29 [updated 2025 May 15]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, 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/NBK114459/
PubMed 23193613Sarkozy A, Deschauer M, Carlier RY, Schrank B, Seeger J, Walter MC, Schoser B, Reilich P, Leturq F, Radunovic A, Behin A, Laforet P, Eymard B, Schreiber H, Hicks D, Vaidya SS, Glaser D, Carlier PG, Bushby K, Lochmuller H, Straub V. Muscle MRI findings in limb girdle muscular dystrophy type 2L. Neuromuscul Disord. 2012 Oct 1;22 Suppl 2:S122-9. doi: 10.1016/j.nmd.2012.05.012.
PubMed 22980763Ten Dam L, van der Kooi AJ, Rovekamp F, Linssen WH, de Visser M. Comparing clinical data and muscle imaging of DYSF and ANO5 related muscular dystrophies. Neuromuscul Disord. 2014 Dec;24(12):1097-102. doi: 10.1016/j.nmd.2014.07.004. Epub 2014 Aug 1.
PubMed 25176504Silva AMS, Coimbra-Neto AR, Souza PVS, Winckler PB, Goncalves MVM, Cavalcanti EBU, Carvalho AADS, Sobreira CFDR, Camelo CG, Mendonca RDH, Estephan EDP, Reed UC, Machado-Costa MC, Dourado-Junior MET, Pereira VC, Cruzeiro MM, Helito PVP, Aivazoglou LU, Camargo LVD, Gomes HH, Camargo AJSD, Pinto WBVDR, Badia BML, Libardi LH, Yanagiura MT, Oliveira ASB, Nucci A, Saute JAM, Franca-Junior MC, Zanoteli E. Clinical and molecular findings in a cohort of ANO5-related myopathy. Ann Clin Transl Neurol. 2019 Jul;6(7):1225-1238. doi: 10.1002/acn3.50801. Epub 2019 Jun 11.
PubMed 31353849Mahjneh I, Bashir R, Kiuru-Enari S, Linssen W, Lamminen A, Visser Md. Selective pattern of muscle involvement seen in distal muscular dystrophy associated with anoctamin 5 mutations: a follow-up muscle MRI study. Neuromuscul Disord. 2012 Oct 1;22 Suppl 2:S130-6. doi: 10.1016/j.nmd.2012.02.007.
PubMed 22980764Khawajazada T, Kass K, Rudolf K, de Stricker Borch J, Sheikh AM, Witting N, Vissing J. Muscle involvement assessed by quantitative magnetic resonance imaging in patients with anoctamin 5 deficiency. Eur J Neurol. 2021 Sep;28(9):3121-3132. doi: 10.1111/ene.14979. Epub 2021 Jul 11.
PubMed 34145687Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmuller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PLoS One. 2013 Aug 14;8(8):e70993. doi: 10.1371/journal.pone.0070993. eCollection 2013.
PubMed 23967145
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MRI-phenotyping of Patients With Pathogenic Anoctamin 5 Variants
- ClinicalTrials.gov ID
- NCT05102799
- Acronym / sponsor ID
- ANO5 MRI / 1928485
- Conditions
- Limb Girdle Muscular Dystrophy
- Keywords
- Anoctaminophathies
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 1 Jun 2026 (actual)
- Study completion
- 1 Aug 2026 (estimated)
- First posted
- 2 Nov 2021 (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.
A large cohort of MRI scans from patients with pathogenic variants in the anoctamin 5 gene will be collected through an international collaboration to better describe muscle involvement.
Detailed description
Background:
The anoctamin 5 gene (ANO5) encodes the anoctamine 5 protein that act as a calcium-sensitive chloride channel. The protein is preferentially expressed in skeletal and cardiac muscle and bone and likely acts in the repair of the cell membrane. Pathogenic ANO5 variants inherited in a autosomal recessive trait give rise to three main phenotypes: Limb-girdle muscular dystrophy type R12 (LGMDR12, formerly classified as LGMD2L), Miyoshi distal muscular dystrophy type 3 (MMD3), and asymptomatic hyperCKemia). As the name implies, patients with LGMDR12 are affected more proximally and patients with MMD3 more distally, but the definition and distinction between the two entities is unclear. Men with anoctaminopathy are more severely affected than women. Cardiac disease such as arrhythmias and cardiomyopathy as well as bulbar symptoms or respiratory failure are very rare in anoctaminopathies. Onset is in adulthood and disease progression is slow, generally with a later onset and disease progression than seen in other LGMDs. Ambulation is preserved until late in the disease course.
However, only few studies based on small case series have investigated the phenotype of patients with ANO5 mutations using MRI. There is therefore a need to investigate a larger international group of patients using MRI to properly describe which muscles are affected in men and women with anoctaminopathy.
The spectrum of phenotypes in anoctaminopathies resembles that seen in dysferlinopathies, and in the latter group, it has been shown that the former division into LGMDR2 (formally LGMD2B) and Miyoshi distal muscular dystrophy type 2 (MMD2) is rather arbitrary. Our hypothesis is that this may very well also be the case for LGMDR12 and MMD3. A large MRI study would be able to shed light on this question. Muscle involvement in patients with ANO5 mutations is said to be asymmetric based on clinical assessments (7,8,10). The proposed study will also elucidate this by studying symmetry of muscle affection. Finally, the diseases severity is said to be marked between the two sexes, but this has not been quantified in any detail before. The proposed study will also be able to shed light on this.
Aim:
The aims of the project are:
- To describe the muscle MRI phenotype in around 200 patients from multiple countries around the world.
- To investigate if it makes sense to group patients with pathogenic ANO5 variants into proximal and distal myopathies.
- To investigate to what extent the disease is asymmetric.
- To investigate the difference in disease severity between sexes.
- To investigate whether a phenotype-genotype correlation exists.
Methods:
Sites from all over the world will share an eCRF and their MRI data with Copenhagen Neuromuscular Center through the platform MyoShare.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anoctaminopathies | – | Other: No interventionAnoctaminopathies including Limb Girdle Muscular Dystrophy R12, Miyoshi distal Muscular Dystrophy type 3 and asymptomatic hyperCKemia |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- MRIs of patients with pathogenic variants in the anoctamin 5 gene will be examined. The MRIs are obtained from either former studies or as part of clinical evaluation in the collaborating countries.
Key inclusion criteria (2 listed)
- Two pathogenic variants in the anoctamin-5 gene
- T1-weighted MR-images of lower back and leg muscles.
Key exclusion criteria (1 listed)
- Concomitant other disorders that also can result in muscular atrophy, i.e. polyneuropathy, other muscle diseases, recent long-term stay in intensive care, among others.
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 |
|---|---|---|
| No interventionNo intervention | Other | Anoctaminopathies |
Primary outcome
Qualitative fat fraction lower back and legs
Time frame: 15 minutes
Qualitative muscle fat fraction analyses of lower back and legs evaluated from T1-weighted images using the Mercury score (score: 0-4)
3 secondary outcomes
Qualitative fat fraction of whole body
Time frame: 15 minutes
Quantitative fat fraction of axial and leg muscles
Time frame: 60 minutes
Inflammatory evaluation of axial and leg muscles
Time frame: 60 minutes
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Background: PubMed 23169617Little AA, McKeever PE, Gruis KL. Novel mutations in the Anoctamin 5 gene (ANO5) associated with limb-girdle muscular dystrophy 2L. Muscle Nerve. 2013 Feb;47(2):287-91. doi: 10.1002/mus.23542. Epub 2012 Nov 21.
- Background: PubMed 23670307Witting N, Duno M, Petri H, Krag T, Bundgaard H, Kober L, Vissing J. Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression. J Neurol. 2013 Aug;260(8):2084-93. doi: 10.1007/s00415-013-6934-y. Epub 2013 May 14.
- Background: PubMed 23193613Palmio J, Penttila S, Jokela M. ANO5-Related Muscle Disease. 2012 Nov 29 [updated 2025 May 15]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, 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/NBK114459/
- Background: PubMed 22980763Sarkozy A, Deschauer M, Carlier RY, Schrank B, Seeger J, Walter MC, Schoser B, Reilich P, Leturq F, Radunovic A, Behin A, Laforet P, Eymard B, Schreiber H, Hicks D, Vaidya SS, Glaser D, Carlier PG, Bushby K, Lochmuller H, Straub V. Muscle MRI findings in limb girdle muscular dystrophy type 2L. Neuromuscul Disord. 2012 Oct 1;22 Suppl 2:S122-9. doi: 10.1016/j.nmd.2012.05.012.
- Background: PubMed 25176504Ten Dam L, van der Kooi AJ, Rovekamp F, Linssen WH, de Visser M. Comparing clinical data and muscle imaging of DYSF and ANO5 related muscular dystrophies. Neuromuscul Disord. 2014 Dec;24(12):1097-102. doi: 10.1016/j.nmd.2014.07.004. Epub 2014 Aug 1.
- Background: PubMed 31353849Silva AMS, Coimbra-Neto AR, Souza PVS, Winckler PB, Goncalves MVM, Cavalcanti EBU, Carvalho AADS, Sobreira CFDR, Camelo CG, Mendonca RDH, Estephan EDP, Reed UC, Machado-Costa MC, Dourado-Junior MET, Pereira VC, Cruzeiro MM, Helito PVP, Aivazoglou LU, Camargo LVD, Gomes HH, Camargo AJSD, Pinto WBVDR, Badia BML, Libardi LH, Yanagiura MT, Oliveira ASB, Nucci A, Saute JAM, Franca-Junior MC, Zanoteli E. Clinical and molecular findings in a cohort of ANO5-related myopathy. Ann Clin Transl Neurol. 2019 Jul;6(7):1225-1238. doi: 10.1002/acn3.50801. Epub 2019 Jun 11.
- Background: PubMed 22980764Mahjneh I, Bashir R, Kiuru-Enari S, Linssen W, Lamminen A, Visser Md. Selective pattern of muscle involvement seen in distal muscular dystrophy associated with anoctamin 5 mutations: a follow-up muscle MRI study. Neuromuscul Disord. 2012 Oct 1;22 Suppl 2:S130-6. doi: 10.1016/j.nmd.2012.02.007.
- Background: PubMed 34145687Khawajazada T, Kass K, Rudolf K, de Stricker Borch J, Sheikh AM, Witting N, Vissing J. Muscle involvement assessed by quantitative magnetic resonance imaging in patients with anoctamin 5 deficiency. Eur J Neurol. 2021 Sep;28(9):3121-3132. doi: 10.1111/ene.14979. Epub 2021 Jul 11.
- Background: PubMed 23967145Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmuller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PLoS One. 2013 Aug 14;8(8):e70993. doi: 10.1371/journal.pone.0070993. eCollection 2013.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Limb Girdle Muscular Dystrophy, 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 2 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: under way, not looking for participants, as of the sponsor's last update on 12 Aug 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Qualitative fat fraction lower back and legs (time frame: 15 minutes). 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 NCT05102799, which also lists 9 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 12 Aug 2026.