mtDNA Mutation Load Analysis in Mesoangioblasts

NCT05199740 | Recruiting DMC

• 1 other identifier: NL78411.068.21
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Mitochondrial Myopathies

Outcome Measures

Primary Outcomes (1)

• Assess mtDNA mutation load in mesoangioblasts

  Isolate mesoangioblasts and quantify mtDNA mutation load using GeneScan analysis

  1 day

Secondary Outcomes (7)

• Assess level of systemic inflammation marker TNFa in blood plasma

  1 day

• Assess level of systemic tissue damage marker CK in blood plasma

  1 day

• Assess level of systemic inflammation marker IL-6 in blood plasma

  1 day

• Assess level of systemic inflammation marker SDF-1 in blood plasma

  1 day

• Assess mitochondrial function in mesoangioblasts

  1 day

Study Arms (1)

mtDNA mutation carriers

Carriers of a pathogenic mtDNA mutation

Other: in vitro analysis

Interventions

in vitro analysis OTHER

in vitro analysis of mesoangioblasts from mtDNA mutation carriers

mtDNA mutation carriers

Eligibility Criteria

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

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.

You may qualify if:

• Written informed consent
• Age: 18+
• Sex: male/female
• Carriers of a heteroplasmic mtDNA mutation load \>20% in skeletal muscle or \>1% in blood

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Maastricht University: lead

Study Sites (1)

Maastricht University

Maastricht, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

muscle derived cells

MeSH Terms

Conditions

Mitochondrial Myopathies

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Janneke Hoeijmakers, PhD, MD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Florence van Tienen, PhD

CONTACT

314332918; florence.vantienen@maastrichtuniversity.nl

Bert Smeets, Prof.

CONTACT

314331995; bert.smeets@maastrichtuniversity.nl

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: January 20, 2022
• Study Start: December 20, 2022
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: January 24, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)