A 5-year Natural History Study in LAMA2-related Muscular Dystrophy and SELENON-related Myopathy.

NCT06132750 | Recruiting

• 1 other identifier: NL84381.091.23
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

SELENON-related myopathy (SELENON-RM) and LAMA2-related muscular dystrophy (LAMA2-MD) are congenital neuromuscular disorders presenting with slowly, progressive axial muscle weakness, spinal rigidity, scoliosis and respiratory insufficiency. Currently, no curative treatment options exist, yet promising preclinical trials are ongoing. Clinical trials are expected to start within 5 years. Natural history data and outcome measures for measuring therapy effectiveness were lacking. Therefore, the LAST STRONG Study (a 1.5-year natural history study) started in 2020. With the extended LAST STRONG Study, we aim to further analyze and expand the 1.5-year natural history data on SELENON-RM or LAMA2-MD to provide a detailed clinical description of the Dutch and Flemish cohort. This will enable a smooth transition towards implementation into clinical care and clinical trials. The extended LAST STRONG Study is a prospective, observational natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM and LAMA2-MD. Patients will be invited to visit our hospital two times (3- and 5-years) after the first visit in the LAST STRONG Study. During both visits, patients will undergo a subset of tests (neurological examination, functional measurements, questionnaires, muscle ultrasound, MRI, pulmonary assessment and accelerometry). All measurements are adapted to the patient's age and functional disabilities.

Conditions

LAMA2-related Muscular Dystrophy; SELENON-related Myopathy

Outcome Measures

Primary Outcomes (1)

• Change of Motor Function Measure (MFM)-32 (older than 7 years) of MFM-20 (2 to 7 years old)

  Global motor functioning. The items of the MFM are classified in 3 domains: D1: standing and transfers, D2: Axial and proximal motor function, D3: Distal motor function. Higher scored indicate a better outcome. The range of the total score is 0-96. The main point of interest includes the change of MFM score over a period of 5 years.

  Change from baseline to 3 years and 5 years

Secondary Outcomes (31)

• Change of physical activity in daily life assessed by an accelerometer (GENEActiv original devices) for 7 days

  Change from baseline to 3 years and 5 years

• Change of activity limitations assessed using ACTIVLIM (6 years and older)

  Change from baseline at 3 years and 5 years

• Change of bone density assessed using DEXA-scan (2 years and older)

  Change from baseline at 3 years and 5 years

• Change of The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score (children under the age of 2 years)

  Change from baseline at 3 years and 5 years

• Change of fatigue (pediatric 2-17 years old) assessed by PedsQL Multidimensional Fatigue Scale (MFS)

  Change from baseline at 3 years and 5 years

Study Arms (1)

SELENON-related myopathy or LAMA2-related muscular dystrophy

Participants diagnosed with congenital myopathy/muscular dystrophy due to mutations in the SEPN1 (SELENON) or LAMA2 gene Interventions: No intervention

Other: No intervention

Interventions

No intervention OTHER

No intervention

SELENON-related myopathy or LAMA2-related muscular dystrophy

Eligibility Criteria

• Age: 1 Day - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

SELENON-RM patients (prevalence: 0.5 in 1.000.000) and LAMA2-RM patients (prevalence: 4 in 500.000) are rare and no Dutch registry exists. Therefore, the investigators can only estimate the number of patients in the Netherlands and Belgium. All patients with SELENON-RM and LAMA2-MD mutations will be identified through contact with genetic diagnostic services, rehabilitation centers, and muscle disease experts in The Netherlands and Dutch-speaking Belgium. In the LAST STRONG Study, 27 LAMA2-MD patients (21±13 years) and 11 SELENON-RM (20±13 years) patients were included. Based on this high participation rate and the minimal loss from follow-up, we expect between 35 to 40 patients to participate in the extended LAST STRONG Study.

You may qualify if:

• Willing and able to complete (part of) the measurement protocol at the Radboudumc, Nijmegen. If patients do not wish or not able to visit our neuromuscular center, they are offered to participate in our study through home visits.
• Genetic conformation of LAMA2-related muscular dystrophy or SELENON-related myopathy by two recessive (likely) pathologic mutations in the LAMA2 or SELENON gene.
• Typical clinical and histological characteristics combined with genetic confirmation in a first degree relative.
• Dutch speaking

You may not qualify if:

• Insufficient understanding of the Dutch language

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboudumc

Nijmegen, Gelderland, 6525GA, Netherlands

RECRUITING

Related Publications (1)

• de Laat ECM, Houwen-van Opstal SLS, Bouman K, van Doorn JLM, Cameron D, van Alfen N, Dittrich ATM, Kamsteeg EJ, Smeets HJM, Groothuis JT, Erasmus CE, Voermans NC. A 5-year natural history study in LAMA2-related muscular dystrophy and SELENON-related myopathy: the Extended LAST STRONG study. BMC Neurol. 2024 Oct 23;24(1):409. doi: 10.1186/s12883-024-03852-4.

  PMID: 39443859 DERIVED

MeSH Terms

Conditions

Muscular dystrophy congenital, merosin negative

Central Study Contacts

Ilse de Laat

CONTACT

+31611469112; ilse.delaat@radboudumc.nl

Nicol Voermans, MD PhD

CONTACT

+31650155770; nicol.voermans@radboudumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: November 15, 2023
• Study Start: October 6, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 15, 2023

Record last verified: 2023-09

Locations

NL (1)