MDC1ANCT06582537
LAMA2 Genetic Correction
An observational study of MDC1A, run by Maastricht University at 1 site in Netherlands.
Trial summary
Merosin-deficient congenital muscle dystrophy type 1a (MDC1a), or LAMA2 muscular dystrophy (LAMA2-MD) is a severe autosomal recessive form of muscular dystrophy that is caused by homozygous or compound heterozygous mutations in the laminin alpha 2 (LAMA-2) gene. Many different LAMA-2 mutations have been reported. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- MDC1A
- What is being tested?
- Participants sample collection
- Type of treatment
- Surgery or procedure
- How many people
- 7 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jul 2020to 18 Jul 2024
- 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: The study will only include patients/controls living in The Netherlands
Who may be able to join
- LAMA2 mutation carriers:
- Age >18 years
- Heterozygous or homozygous LAMA2 c.5562+5G>C mutation
- Written informed consent
- Controls:
- Written informed consent
- Age >18 years
- No muscular dystrophy or other disease known to affect muscle morphology or function
Who cannot join
- MDC1a patients and controls:
- No informed consent
- Use of anti-coagulants, anti-thrombotics and other medication influencing coagulation
- Have a weekly alcohol intake of ≥ 35 units (men) or ≥ 24 units (women)
- Current history of drug abuse
- A history of strokes
Show all 12Show fewer
- Significant concurrent illness
- Ongoing participation in other clinical trials
- Major surgery within 4 weeks of the visit
- Pregnant or lactating women
- Patients unable and/or unwilling to comply with treatment and study instructions
- Any other factor that in the opinion of the investigator excludes the patient from the study
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academisch Ziekenhuis Maastricht
Maastricht, Limburg, 6229HX
About this study
Official title: Ex Vivo Genetic Correction of LAMA2 Mutation(s) in Myogenic Stem Cells of Patients with Merosin-deficient Congenital Muscle Dystrophy Type 1a (MDC1a)
Merosin-deficient congenital muscle dystrophy type 1a (MDC1a), or LAMA2 muscular dystrophy (LAMA2-MD) is a severe autosomal recessive form of muscular dystrophy that is caused by homozygous or compound heterozygous mutations in the laminin alpha 2 (LAMA-2) gene. Many different LAMA-2 mutations have been reported. In most cases, MDC1a is diagnosed within the first year of life, and is characterized by hypotonia, delayed motor development and white matter abnormalities. Currently, no efficient treatment is available for this patient group. Generally, MDC1a patients with mutations causing a premature stop codon are most severely affected (early onset LAMA2-MD) and patients with missense mutations are generally affected more mild affected and more late-onset (late onset LAMA2-MD). However, large variation in disease severity and clinical course is observed, even between individuals with the same mutation, e.g. the LAMA2 c.5562+5G>C mutation, which is frequently observed in Dutch MDC1a patients. This study aims to isolate and culture fibroblasts and myogenic stem cells called mesoangioblasts from the skin and muscle biopsies of adult LAMA2 mutation carriers to explore if genetic correction of LAMA2 mutations using CRISPR-Cas9 can be achieved and subsequently assess the effect in vitro, as a first step towards therapy development.
- Conditions
- MDC1A
- Being tested
- Participants sample collection
- Keywords
- MDC1A, LAMA2, Muscular Dystrophy, Mesoangioblasts
- Medical subject headings
- Muscular Dystrophies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Participants sample collectionProcedure or surgery
A skeletal muscle biopsy and a venous blood sample will be collected. The skin biopsy will be obtained during the incision needed for the muscle biopsy.
| Study group | Role | What they receive |
|---|---|---|
| Adult carriers of the LAMA2 c.5562+5G>C mutation | Not described Receives: Procedure: Participants sample collection | |
| Healthy controls | Not described Receives: Procedure: Participants sample collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare RNA transcription of corrected and not corrected DNA
qPCR
Measured: 1 day
Assess effect LAMA2 mutations on muscle protein quantity (amount of LAMA2)
LAMA2 immunostaining
Measured: 1 day
Assess effect LAMA2 mutations on muscle protein quality (localization of LAMA2)
LAMA2 immunostaining
Measured: 1 day
Assess effect LAMA2 mutations on muscle protein quantity (LAMA2 overall levels)
LAMA2 western blot
Measured: 1 day
Assess effect LAMA2 mutations on muscle protein quality (fibrosis)
LAMA2 HE staining
Measured: 1 day
Secondary outcomes (5)
Verification of the LAMA2 mutations or exclusion of LAMA2 mutations in controls
DNA analysis
Measured: 1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: CK
ELISA assay
Measured: 1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: TNFa
ELISA assay
Measured: 1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: IL-6
ELISA assay
Measured: 1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: SDF1
ELISA assay
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2024
- Study start1 Jul 2020
- Primary completion18 Jul 2024
- Study completion18 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MDC1AStudies 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-control
- Time perspective
- Cross-sectional
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06582537
- Sponsor's protocol ID
- MABS03
- Status last verified
- Jul 2024
- First submitted
- 11 Jan 2022
- Last updated
- 3 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- 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 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ex Vivo Genetic Correction of LAMA2 Mutation(s) in Myogenic Stem Cells of Patients with Merosin-deficient Congenital Muscle Dystrophy Type 1a (MDC1a)
- ClinicalTrials.gov ID
- NCT06582537
- Acronym / sponsor ID
- MABS03
- Conditions
- MDC1A
- Keywords
- MDC1A, LAMA2, Muscular Dystrophy, Mesoangioblasts
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 18 Jul 2024 (actual)
- Study completion
- 18 Jul 2024 (actual)
- First posted
- 3 Sep 2024 (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.
Merosin-deficient congenital muscle dystrophy type 1a (MDC1a), or LAMA2 muscular dystrophy (LAMA2-MD) is a severe autosomal recessive form of muscular dystrophy that is caused by homozygous or compound heterozygous mutations in the laminin alpha 2 (LAMA-2) gene. Many different LAMA-2 mutations have been reported. In most cases, MDC1a is diagnosed within the first year of life, and is characterized by hypotonia, delayed motor development and white matter abnormalities. Currently, no efficient treatment is available for this patient group. Generally, MDC1a patients with mutations causing a premature stop codon are most severely affected (early onset LAMA2-MD) and patients with missense mutations are generally affected more mild affected and more late-onset (late onset LAMA2-MD). However, large variation in disease severity and clinical course is observed, even between individuals with the same mutation, e.g. the LAMA2 c.5562+5G>C mutation, which is frequently observed in Dutch MDC1a patients. This study aims to isolate and culture fibroblasts and myogenic stem cells called mesoangioblasts from the skin and muscle biopsies of adult LAMA2 mutation carriers to explore if genetic correction of LAMA2 mutations using CRISPR-Cas9 can be achieved and subsequently assess the effect in vitro, as a first step towards therapy development.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adult carriers of the LAMA2 c.5562+5G>C mutation | – | Procedure: Participants sample collection |
| Healthy controls | – | Procedure: Participants sample collection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study will only include patients/controls living in The Netherlands
Key inclusion criteria (8 listed)
- LAMA2 mutation carriers:
- Age >18 years
- Heterozygous or homozygous LAMA2 c.5562+5G>C mutation
- Written informed consent
- Written informed consent
Key exclusion criteria (12 listed)
- MDC1a patients and controls:
- No informed consent
- Use of anti-coagulants, anti-thrombotics and other medication influencing coagulation
- Have a weekly alcohol intake of ≥ 35 units (men) or ≥ 24 units (women)
- Current history of drug abuse
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 |
|---|---|---|
| Participants sample collectionA skeletal muscle biopsy and a venous blood sample will be collected. The skin biopsy will be obtained during the incision needed for the muscle biopsy. | Procedure or surgery | Adult carriers of the LAMA2 c.5562+5G>C mutation, Healthy controls |
Primary outcome
Compare RNA transcription of corrected and not corrected DNA
Time frame: 1 day
qPCR
Assess effect LAMA2 mutations on muscle protein quantity (amount of LAMA2)
Time frame: 1 day
LAMA2 immunostaining
Assess effect LAMA2 mutations on muscle protein quality (localization of LAMA2)
Time frame: 1 day
LAMA2 immunostaining
Assess effect LAMA2 mutations on muscle protein quantity (LAMA2 overall levels)
Time frame: 1 day
LAMA2 western blot
Assess effect LAMA2 mutations on muscle protein quality (fibrosis)
Time frame: 1 day
LAMA2 HE staining
5 secondary outcomes
Verification of the LAMA2 mutations or exclusion of LAMA2 mutations in controls
Time frame: 1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: CK
Time frame: 1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: TNFa
Time frame: 1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: IL-6
Time frame: 1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: SDF1
Time frame: 1 day
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 3 Sep 2024.
- 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 MDC1A, run by Maastricht University at 1 site in Netherlands.
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 8 inclusion and 12 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 3 Sep 2024. 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 Netherlands. 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?
Compare RNA transcription of corrected and not corrected DNA (time frame: 1 day). The study lists 5 primary outcomes in all. 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 3 Sep 2024.