The Natural History of Mitochondrial Diseases

NCT06504433 | Recruiting

• 1 other identifier: 2024_ETH00044
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

The Natural History of Mitochondrial (MITO) Diseases (a longitudinal study observing the natural history of mitochondrial diseases) The goal of this observational study (non-randomised retrospective and prospective) is to fully characterise primary MITO disease; that includes both sexes/genders, over 18 years of age and healthy volunteers\]. The main question\[s\] it aims to answer is to: • better characterise MITO phenotypes (organ involvement, severity, progression) and collect biospecimens to create a biobank that can be used for future biomarker discovery to improve early diagnosis, prognostication and management of mitochondrial disease. The study will be a longitudinal, retrospective, prospective, observational study of participants (400) with confirmed MITO and relevant controls followed for up to 10 years. Data will be collected at regularly scheduled standard-of-care (SOC), 6 to 12 monthly appointments. The 100 control participants will therefore be comprised of (i) unaffected asymptomatic family members of MITO participants with no genetic risk; (ii) participants with non-MITO movement disorders that are not classified as MITO by their clinical presentation and genetic tests (for example Parkinson's disease) and/or (iii) age-matched healthy controls recruited from the NeuRA database of volunteers. Demographic data, medical history, biochemical, histological, genetic, social and other clinical SOC data will be collected. Additionally, seizure and migraine frequency in participants who experience these, will be collected and a quality-of-life questionnaire (SF-12v2), as part of the validated neurological assessment using the Newcastle Mitochondrial Disease Adult Scale (NMDAS).

Conditions

Mitochondrial Diseases; Neurological Diseases or Conditions; Genetic Disease

Outcome Measures

Primary Outcomes (1)

• Descriptive measures: The natural history of mitochondrial disease

  The primary outcome measure is the creation of a clinical database and biospecimen repository (biobank) with medical, health and lifestyle data to characterise the natural history of mitochondrial disease for each MITO patient. Data will be stratified by disease genotype, phenotype, age of onset, sequence and timing of major symptom onset, severity and progression of organ involvement and symptom progression, to identify any associations between parameters.

  10 years

Secondary Outcomes (1)

• The natural history of mitochondrial disease

  10 years

Study Arms (3)

MITO participants/patients

400 MITO patients will be observed over 10 years and having a confirmed variant/deletion in either nuclear or mitochondrial genes involved in the mitochondrial respiratory chain, or patients meeting the clinical diagnostic criteria for MITO using consensus scoring systems such as the Walker Criteria, or the Nijmegen criteria

Diagnostic Test: Confirmed variant/deletion in either nuclear or mitochondrial genes involved in the mitochondrial respiratory chain

Patients with a clinically confirmed non-MITO neuromuscular disorder

The study will form a 10-year, longitudinal, non-randomised, retrospective, and prospective, observational study of patients with MITO using controls who may be: * asymptomatic biological relatives of MITO participants/patients * patients with a clinically confirmed non-MITO neuromuscular disorder, or

Diagnostic Test: Confirmed variant/deletion in either nuclear or mitochondrial genes involved in the mitochondrial respiratory chain

Age and gender-matched healthy controls.

Age/gender-matched healthy controls will be recruited from the NeuRA database of volunteers

Diagnostic Test: Confirmed variant/deletion in either nuclear or mitochondrial genes involved in the mitochondrial respiratory chain

Interventions

Confirmed variant/deletion in either nuclear or mitochondrial genes involved in the mitochondrial respiratory chain DIAGNOSTIC_TEST

This is a 10-year, longitudinal, non-randomised, retrospective and prospective, observational study that will be used to characterise the natural history of primary mitochondrial disease (MITO) in 400 participants and their asymptomatic family members (with no genetic risk), non-MITO healthy controls (100 participants) and form a biobank that can be used in future research using separate ethics approved protocols to identify biomarkers of disease onset and progression.

Age and gender-matched healthy controls.; MITO participants/patients; Patients with a clinically confirmed non-MITO neuromuscular disorder

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants (at least 400) with confirmed MITO (on genetic/clinical grounds) will be recruited into this study through NeuRA, Randwick, NSW by CI/CPI Professor Carolyn Sue AM FAHMS. The study will recruit 100 control participants who may be: i. age and gender-matched healthy controls from the NeuRA database of volunteers; ii. asymptomatic relatives of MITO participants or iii. non-MITO movement disorder controls recruited from other clinics at NeuRA.

You may qualify if:

• A clinical and/or genetically confirmed diagnosis of MITO.
• Individuals \> 18 years of age, managed by a specialist neurologist, with confirmed MITO
• Control participants will comprise asymptomatic relatives of confirmed MITO patients with no clinical or genetic evidence of MITO; clinically confirmed non-MITO movement disease controls (from other clinics at NeuRA) or age/gender-matched healthy participants.

You may not qualify if:

• Not willing to participate in the AMDC Clinical Registry
• Not willing to undergo genetic testing
• Not willing to provide consent

Sponsors & Collaborators

• Neuroscience Research Australia: lead

Study Sites (1)

Neuroscience Research Australia

Randwick, New South Wales, 2031, Australia

RECRUITING

Related Publications (3)

• Davis RL, Liang C, Sue CM. A comparison of current serum biomarkers as diagnostic indicators of mitochondrial diseases. Neurology. 2016 May 24;86(21):2010-5. doi: 10.1212/WNL.0000000000002705. Epub 2016 Apr 27.

  PMID: 27164684 BACKGROUND

• Davis RL, Liang C, Sue CM. Mitochondrial diseases. Handb Clin Neurol. 2018;147:125-141. doi: 10.1016/B978-0-444-63233-3.00010-5.

  PMID: 29325608 BACKGROUND

• Sue CM, Balasubramaniam S, Bratkovic D, Bonifant C, Christodoulou J, Coman D, Crawley K, Edema-Hildebrand F, Ellaway C, Ghaoui R, Kava M, Kearns LS, Lee J, Liang C, Mackey DA, Murray S, Needham M, Rius R, Russell J, Smith NJC, Thyagarajan D, Wools C. Patient care standards for primary mitochondrial disease in Australia: an Australian adaptation of the Mitochondrial Medicine Society recommendations. Intern Med J. 2022 Jan;52(1):110-120. doi: 10.1111/imj.15505. Epub 2021 Nov 19.

  PMID: 34505344 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

MITO and control Participants (asymptomatic, unaffected family members, or patients with non-MITO movement disorder), the following biospecimens will be collected to form the biobank for DNA extraction, biomarker and heteroplasmy analysis: 1. Whole blood collection (60ml every 6 months ii. Plasma and serum iii. PBMCs will be extracted for transcriptomics, proteomics and possible cell line iv. development 2. Skin biopsies will be used to create fibroblast cells 3. Hair follicles 4. Urine and urinary epithelial cells every 6 months will be used for autofluorescence analysis, metabolomics, biomarker development and DNA extraction 5. Saliva/Buccal cells 6. Stool will be collected, via a home collection kit, every 6 to 12 months, for microbiome analysis.

MeSH Terms

Conditions

Mitochondrial Diseases; Genetic Diseases, Inborn

Interventions

Sequence Deletion

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Mutation; Genetic Variation; Genetic Phenomena; Mutagenesis

Study Officials

• Carolyn M Sue, MBBS

  Kinghorn Chair, Neuroscience Research Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Belinda Di Bartolo

CONTACT

61 2 9399 1835; b.dibartolo@neura.edu.au

Vyoma Patel, PhD

CONTACT

+6123991676; v.patel@neura.edu.au

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 16, 2024
• Study Start: May 7, 2024
• Primary Completion (Estimated): May 7, 2029
• Study Completion (Estimated): May 7, 2034
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

AU (1)