Mitochondrial MyopathiesMABS05NCT05199740
mtDNA Mutation Load Analysis in Mesoangioblasts
An observational study of Mitochondrial Myopathies, run by Maastricht University at 1 site in Netherlands.
Trial summary
Mitochondrial diseases caused by defects in oxidative phosphorylation (OXPHOS) due to heteroplasmic mitochondrial DNA (mtDNA) mutations are rare (frequency 1/5,000), but severe multi-system disorders. Clinical manifestations are highly variable, but predominantly affect energy demanding tissues, like brain and muscle. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mitochondrial Myopathies
- What is being tested?
- in vitro analysis
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 20 Dec 2022to 1 Jul 2026
- 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
- No healthy volunteers
- Adult, Older adult
Study population: In the study, the following study population will be included: Adult males and females with a heteroplasmic mitochondrial mtDNA mutation identified in blood and/or skeletal muscle. Mitochondrial disorders due to a mtDNA mutation are very heterogeneous and carriers can present a variety of clinical symptoms and at varying age. The mtDNA mutation can be identified via diagnostic mtDNA analysis upon suspected or biochemically confirmed mitochondrial disease. Alternatively, given the maternal inheritance of the mtDNA, the mutation can be identified in (currently) unaffected siblings or children of a clinically affected mtDNA mutation carrier.
Who may be able to join
- Written informed consent
- Age: 18+
- Sex: male/female
- Carriers of a heteroplasmic mtDNA mutation load >20% in skeletal muscle or >1% in blood
Who cannot join
- 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
- Significant concurrent illness
Show all 10Show fewer
- Ongoing participation in other clinical trials that contain an intervention
- Major surgery within 4 weeks of the visit
- Pregnant or lactating women
- Patients unable and/or unwilling to comply with treatment and study instructions
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht University
Maastricht
Florence Dept. Toxicogenomics, PhD, 0433882918, florence.vantienen@maastrichtuniversity.nl
About this study
Official title: Assess the mtDNA Mutation Load in Mesoangioblasts of mtDNA Mutation Carriers
Mitochondrial diseases caused by defects in oxidative phosphorylation (OXPHOS) due to heteroplasmic mitochondrial DNA (mtDNA) mutations are rare (frequency 1/5,000), but severe multi-system disorders. Clinical manifestations are highly variable, but predominantly affect energy demanding tissues, like brain and muscle. Myopathy is a common feature of mtDNA disorders, being present in more than 50% of the mtDNA mutation carriers, and seriously affects patients' general well-being and quality of life. Currently, no treatment is available for these patients, although the induction of muscle regeneration by exercise treatment has been shown to alleviate their myopathy. This implies that these patients can produce muscle fibres that perform better, most likely because the mutation load is lower. Mesoangioblasts (MABs) are myogenic precursors that have been recognized as a source for development of a systemic myogenic stem-cell therapy. Autologous MABs may be feasible for half of the mtDNA mutation carriers of 6 different mtDNA mutations, as their mtDNA mutation load in mesoangioblasts was (nearly) absent (<10%). However, there are many more mtDNA mutations in the 16.5kb mtDNA and the aim of this study is to determine the mtDNA mutation load in mesoangioblasts of other mtDNA mutation carriers and identify the patients or mutations for which this is a feasible approach.
Read the detailed description
Rationale: Mitochondrial diseases caused by defects in oxidative phosphorylation (OXPHOS) due to heteroplasmic mitochondrial DNA (mtDNA) mutations are rare (frequency 1/5,000), but severe multi-system disorders. Clinical manifestations are highly variable, but predominantly affect energy demanding tissues, like brain and muscle. Myopathy is a common feature of mtDNA disorders, being present in more than 50% of the mtDNA mutation carriers, and seriously affects patients' general well-being and quality of life. Currently, no treatment is available for these patients, although the induction of muscle regeneration by exercise treatment has been shown to alleviate their myopathy. This implies that these patients can produce muscle fibres that perform better, most likely because the mutation load is lower. Mesoangioblasts (MABs) are myogenic precursors that have been recognized as a source for development of a systemic myogenic stem-cell therapy, and allogeneic transplantation has been successfully applied to mice and dogs with Duchenne muscular dystrophy. A subsequent phase I/II clinical study in boys with DMD demonstrated that donor MABs treatment was relatively safe, but did not result in clinical improvement, which can partly be attributed to the required use of immunosuppressive agents. The use of autologous MABs would circumvent this and a previous study of our group demonstrated that this is feasible for half of the mtDNA mutation carriers of 6 different mtDNA mutations, as their mtDNA mutation load in mesoangioblasts was (nearly) absent (<10%). However, there are many more mtDNA mutations in the 16.5kb mtDNA and the aim of this study is to determine the mtDNA mutation load in mesoangioblasts of other mtDNA mutation carriers and identify the patients or mutations for which this is a feasible approach.
Objective: The primary objectives of this project is to assess the mtDNA mutation load in mesoangioblasts of mtDNA mutation carriers and identify which patients display no/low (<10%) mtDNA mutation load in mesoangioblasts. Secondary objectives aim at determining the proliferation, myogenic differentiation and OXPHOS capacity of mesoangioblasts, their systemic inflammation status and assessment of the mtDNA mutation load in satellite cells.
Study design: Mono-centre observation study. Study population: 30 adult carriers of a heteroplasmic mtDNA point-mutation or large-scale mtDNA deletion (>2kb).
Intervention: From each participant, a 30mg skeletal muscle biopsy and a 20ml venous blood sample will be collected.
Main study parameters/endpoints: Assess the mtDNA mutation load in skeletal muscle derived mesoangioblasts.
- Conditions
- Mitochondrial Myopathies
- Being tested
- in vitro analysis
- Medical subject headings
- Mitochondrial Myopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
in vitro analysisOther
in vitro analysis of mesoangioblasts from mtDNA mutation carriers
| Study group | Role | What they receive |
|---|---|---|
| mtDNA mutation carriers | Carriers of a pathogenic mtDNA mutation Receives: Other: in vitro analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess mtDNA mutation load in mesoangioblasts
Isolate mesoangioblasts and quantify mtDNA mutation load using GeneScan analysis
Measured: 1 day
Secondary outcomes (7)
Assess level of systemic inflammation marker TNFa in blood plasma
TNFa measurement in plasma (pg/ml)
Measured: 1 day
Assess level of systemic tissue damage marker CK in blood plasma
CK measurement in plasma (U/l)
Measured: 1 day
Assess level of systemic inflammation marker IL-6 in blood plasma
IL-6 measurement in plasma (pg/ml)
Measured: 1 day
Assess level of systemic inflammation marker SDF-1 in blood plasma
SDF-1 measurement in plasma (pg/ml)
Measured: 1 day
Assess mitochondrial function in mesoangioblasts
Assess mtDNA copynumber and OXPHOS capacity in mesoangioblasts
Measured: 1 day
Assess myogenic differentiation capacity of mesoangioblasts
Assess myogenic fusion index of mesoangioblasts isolated from a muscle biopsy
Measured: 1 day
Assess mtDNA mutation load in satellite cells
Isolate satellite cells and quantify mtDNA mutation load using GeneScan analysis
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 posted20 Jan 2022
- Study start20 Dec 2022
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial MyopathiesStudies 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Janneke Hoeijmakers, PhD, MD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05199740
- Sponsor's protocol ID
- NL78411.068.21
- Acronym
- MABS05
- Status last verified
- Jan 2024
- First submitted
- 17 Dec 2021
- Last updated
- 24 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 24 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assess the mtDNA Mutation Load in Mesoangioblasts of mtDNA Mutation Carriers
- ClinicalTrials.gov ID
- NCT05199740
- Acronym / sponsor ID
- MABS05 / NL78411.068.21
- Conditions
- Mitochondrial Myopathies
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Study start
- 20 Dec 2022 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Jul 2026 (estimated)
- First posted
- 20 Jan 2022 (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.
Mitochondrial diseases caused by defects in oxidative phosphorylation (OXPHOS) due to heteroplasmic mitochondrial DNA (mtDNA) mutations are rare (frequency 1/5,000), but severe multi-system disorders. Clinical manifestations are highly variable, but predominantly affect energy demanding tissues, like brain and muscle. Myopathy is a common feature of mtDNA disorders, being present in more than 50% of the mtDNA mutation carriers, and seriously affects patients' general well-being and quality of life. Currently, no treatment is available for these patients, although the induction of muscle regeneration by exercise treatment has been shown to alleviate their myopathy. This implies that these patients can produce muscle fibres that perform better, most likely because the mutation load is lower. Mesoangioblasts (MABs) are myogenic precursors that have been recognized as a source for development of a systemic myogenic stem-cell therapy. Autologous MABs may be feasible for half of the mtDNA mutation carriers of 6 different mtDNA mutations, as their mtDNA mutation load in mesoangioblasts was (nearly) absent (<10%). However, there are many more mtDNA mutations in the 16.5kb mtDNA and the aim of this study is to determine the mtDNA mutation load in mesoangioblasts of other mtDNA mutation carriers and identify the patients or mutations for which this is a feasible approach.
Detailed description
Rationale: Mitochondrial diseases caused by defects in oxidative phosphorylation (OXPHOS) due to heteroplasmic mitochondrial DNA (mtDNA) mutations are rare (frequency 1/5,000), but severe multi-system disorders. Clinical manifestations are highly variable, but predominantly affect energy demanding tissues, like brain and muscle. Myopathy is a common feature of mtDNA disorders, being present in more than 50% of the mtDNA mutation carriers, and seriously affects patients' general well-being and quality of life. Currently, no treatment is available for these patients, although the induction of muscle regeneration by exercise treatment has been shown to alleviate their myopathy. This implies that these patients can produce muscle fibres that perform better, most likely because the mutation load is lower. Mesoangioblasts (MABs) are myogenic precursors that have been recognized as a source for development of a systemic myogenic stem-cell therapy, and allogeneic transplantation has been successfully applied to mice and dogs with Duchenne muscular dystrophy. A subsequent phase I/II clinical study in boys with DMD demonstrated that donor MABs treatment was relatively safe, but did not result in clinical improvement, which can partly be attributed to the required use of immunosuppressive agents. The use of autologous MABs would circumvent this and a previous study of our group demonstrated that this is feasible for half of the mtDNA mutation carriers of 6 different mtDNA mutations, as their mtDNA mutation load in mesoangioblasts was (nearly) absent (<10%). However, there are many more mtDNA mutations in the 16.5kb mtDNA and the aim of this study is to determine the mtDNA mutation load in mesoangioblasts of other mtDNA mutation carriers and identify the patients or mutations for which this is a feasible approach.
Objective: The primary objectives of this project is to assess the mtDNA mutation load in mesoangioblasts of mtDNA mutation carriers and identify which patients display no/low (<10%) mtDNA mutation load in mesoangioblasts. Secondary objectives aim at determining the proliferation, myogenic differentiation and OXPHOS capacity of mesoangioblasts, their systemic inflammation status and assessment of the mtDNA mutation load in satellite cells.
Study design: Mono-centre observation study. Study population: 30 adult carriers of a heteroplasmic mtDNA point-mutation or large-scale mtDNA deletion (>2kb).
Intervention: From each participant, a 30mg skeletal muscle biopsy and a 20ml venous blood sample will be collected.
Main study parameters/endpoints: Assess the mtDNA mutation load in skeletal muscle derived mesoangioblasts.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| mtDNA mutation carriers | – | Other: in vitro analysisCarriers of a pathogenic mtDNA mutation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- In the study, the following study population will be included: Adult males and females with a heteroplasmic mitochondrial mtDNA mutation identified in blood and/or skeletal muscle. Mitochondrial disorders due to a mtDNA mutation are very heterogeneous and carriers can present a variety of clinical symptoms and at varying age. The mtDNA mutation can be identified via diagnostic mtDNA analysis upon suspected or biochemically confirmed mitochondrial disease. Alternatively, given the maternal inheritance of the mtDNA, the mutation can be identified in (currently) unaffected siblings or children of a clinically affected mtDNA mutation carrier.
Key inclusion criteria (4 listed)
- Written informed consent
- Age: 18+
- Sex: male/female
- Carriers of a heteroplasmic mtDNA mutation load >20% in skeletal muscle or >1% in blood
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| in vitro analysisin vitro analysis of mesoangioblasts from mtDNA mutation carriers | Other | mtDNA mutation carriers |
Primary outcome
Assess mtDNA mutation load in mesoangioblasts
Time frame: 1 day
Isolate mesoangioblasts and quantify mtDNA mutation load using GeneScan analysis
7 secondary outcomes
Assess level of systemic inflammation marker TNFa in blood plasma
Time frame: 1 day
Assess level of systemic tissue damage marker CK in blood plasma
Time frame: 1 day
Assess level of systemic inflammation marker IL-6 in blood plasma
Time frame: 1 day
Assess level of systemic inflammation marker SDF-1 in blood plasma
Time frame: 1 day
Assess mitochondrial function in mesoangioblasts
Time frame: 1 day
Assess myogenic differentiation capacity of mesoangioblasts
Time frame: 1 day
Assess mtDNA mutation load in satellite cells
Time frame: 1 day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 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.
Janneke Hoeijmakers, PhD, MD principal investigator
Maastricht University Medical 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 Mitochondrial Myopathies, 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 4 inclusion and 10 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 24 Jan 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Florence van Tienen, PhD (314332918, florence.vantienen@maastrichtuniversity.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess mtDNA mutation load in mesoangioblasts (time frame: 1 day). 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 24 Jan 2024.