MitochondrialLeuko MitoNCT07868796
Natural History and Genotype-Phenotype Correlations in Mitochondrial Leukoencephalopathies
An observational study of Mitochondrial and Leukoencephalopathies, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 1 site in Italy.
Trial summary
Mitochondrial disorders (MDs) are among the most common inherited metabolic diseases, caused by genetic defects in mitochondrial or nuclear DNA that impair cellular energy production. The central nervous system (CNS) is frequently affected, due to its high energy demands. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Mitochondrial, Leukoencephalopathies, Leukoencephalopathy
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 15 Sep 2025to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patient with a confirmed genetic diagnosis of mitochondrial leukoencephalopathy
Who may be able to join
- Confirmed diagnosis of ML, confirmed by:
- Neuroradiological evidence of a MRI pattern of white matter alterations compatible with leukoencephalopathy
- Genetic evidence of pathogenic variants in nuclear or mitochondrial genes
- Availability of clinical data, including medical records detailing symptom onset, disease progression, neuroimaging findings, and clinical management.
- Written informed consent obtained from the patient or their legal guardian (for minors or individuals with cognitive impairment). If the patient is deceased, consent for the use of medical records in this study will be obtained from the legally authorized representative or next of kin
Who cannot join
- Unconfirmed diagnosis of mitochondrial leukoencephalopathy , including cases where:
- MRI findings do not demonstrate a white matter alteration pattern compatible with leukoencephalopathy
- There is neither genetic confirmation of a pathogenic variant in nuclear or mitochondrial genes
- Insufficient clinical data, including cases where medical records lack essential information on symptom onset, disease progression, neuroimaging findings, or clinical management, preventing a meaningful contribution to the study's objectives.
- Concomitant diagnosis of another genetic disorder that may independently contribute to white matter abnormalities or neurological symptoms, confounding the assessment of ML progression and clinical outcomes
- Unavailability of written informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan
Anna Ardissone, MD, + 39 02.2394, anna.ardissone@istituto-besta.it
About this study
Official title: Natural History and Genotype-Phenotype Correlations in Mitochondrial Leukoencephalopathies: A Multicentric, International Observational Study
Mitochondrial disorders (MDs) are among the most common inherited metabolic diseases, caused by genetic defects in mitochondrial or nuclear DNA that impair cellular energy production. The central nervous system (CNS) is frequently affected, due to its high energy demands. Within the broad clinical spectrum of MDs, mitochondrial leukoencephalopathies (MLs) have emerged as a distinct subgroup characterized by CNS white matter involvement.
MLs are clinically and genetically heterogeneous, with onset ranging from infancy to adulthood. Patients may experience episodes of neurological regression, often triggered by stressors such as febrile illnesses, alongside variable motor, cognitive, and occasionally extraneurological involvement. Neuroimaging typically reveals diffuse or focal white matter abnormalities, including cavitation and rarefaction, with additional involvement of deep gray matter structures. Certain ML subtypes exhibit characteristic MRI patterns that may aid in diagnosis.
Read more
Despite recent advancements in the genetic and neuroradiological characterization of MLs, significant knowledge gaps persist. Although the number of disease-causing genes has increased over the last decades, a comprehensive understanding of genotype-phenotype correlations is still lacking. Additionally, knowledge on the natural history of these disorders is limited. Existing data often focus on imaging findings with insufficient integration of clinical, biochemical, and molecular features, limiting the understanding of disease mechanisms, progression, and therapeutic responses.
In light of these gaps, this multicenter, observational, retrospective study aims to systematically collect and analyze clinical, biochemical, neuroradiological, and genetic data from individuals with MLs, assessed at international reference centers for MDs. The study seeks to better elucidate the phenotypic variability and genotype-phenotype correlations of MLs. This work is expected to enhance diagnostic accuracy, inform management strategies, support prognostic counseling, and ultimately contribute to the better overall management of affected individuals
- Conditions
- Mitochondrial, Leukoencephalopathies, Leukoencephalopathy
- Keywords
- Mitochondrial disorder, leukoencephalopathy, leukodystrophy, mitochondrial leukoencephalopathy
- Medical subject headings
- Leukoencephalopathies, Mitochondrial Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
Comprehensive characterization of genotype-phenotype correlations in MLs.
The primary endpoint for evaluating the principal objective of this study is the comprehensive characterization of genotype-phenotype correlations in MLs. This will be assessed through the collection and analysis of retrospective longitudinal clinical, neuroradiological and genetic data. Clinical phenotypes will then be stratified based on specific underlying genetic defects, assessing their impact on disease onset and progression to establish robust genotype-phenotype correlations.
Data collection will include:
- Family history, including inheritance patterns and consanguinity when applicable.
- Age at symptom onset
- Initial clinical presentation, documenting key symptoms and signs at disease onset.
- Progression of disease manifestations, capturing the evolution of neurological and extraneurological features over time.
- Neuroradiological findings, assessed through MRI scans to evaluate white matter abnormalities, other signal abnormalities or specific MRI findings
Measured: 12 months
Secondary outcomes (8)
The comprehensive characterization of disease progression in MLs, assessed through the collection and analysis of longitudinal clinical, instrumental and genetic data: NMDAS
Disease progression in adults assessed by the Newcastle Mitochondrial Disease Adult Scale (NMDAS) Disease severity and progression in adult participants will be assessed using the Newcastle Mitochondrial Disease Adult Scale (NMDAS).
Unit of Measure: NMDAS total score.
Measured: 12 months
The comprehensive characterization of disease progression in MLs, assessed through the collection and analysis of longitudinal clinical, instrumental and genetic data: Serum lactate levels
Serum lactate levels will be collected and analyzed, when available, to characterize biochemical abnormalities and their changes over time Unit of Measure: nmol/h/mg.
Measured: 12 months
The comprehensive characterization of disease progression in MLs, assessed through the collection and analysis of longitudinal clinical, instrumental and genetic data. : Serum pyruvate levels
Serum pyruvate levels will be collected and analyzed, when available, to characterize biochemical abnormalities and their changes over time Unit of Measure: nmol/h/mg.
Measured: 12 months
Change in disease severity in treated adult participants assessed by NMDAS
In adult participants receiving disease-specific therapeutic interventions as part of their clinical care, changes in disease severity will be assessed using the Newcastle Mitochondrial Disease Adult Scale (NMDAS), when available.
Unit of Measure: NMDAS total score
Measured: 12 months
Change in disease severity in treated pediatric participants assessed by NPMDS
In pediatric participants receiving disease-specific therapeutic interventions as part of their clinical care, changes in disease severity will be assessed using the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS), when available.
NPMDS total score
Measured: 12 months
Change in serum lactate levels in treated participants
In participants receiving disease-specific therapeutic interventions as part of their clinical care, changes in serum lactate levels will be assessed, when available.
Unit of Measure: Serum lactate concentration
Measured: 12 months
Change in serum pyruvate levels in treated participants
In participants receiving disease-specific therapeutic interventions as part of their clinical care, changes in serum pyruvate levels will be assessed, when available.
Unit of Measure: Serum pyruvate concentration
Measured: 12 months
Progression of brain MRI abnormalities in treated participants
In participants receiving disease-specific therapeutic interventions as part of their clinical care, available longitudinal brain MRI examinations will be evaluated for progression of neuroradiological abnormalities.
Unit of Measure: Percentage of participants with radiological progression
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2026
- Study start15 Sep 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for MitochondrialStudies of the same condition, open and under way.
- More trials run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anna Ardissone, MD, Principal investigator, Fondazione IRCCS Istituto Neurologico Carlo Besta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07868796
- Sponsor's protocol ID
- Leuko Mito
- Acronym
- Leuko Mito
- Status last verified
- Feb 2026
- First submitted
- 17 Feb 2026
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Roosendaal SD, van de Brug T, Alves CAPF, Blaser S, Vanderver A, Wolf NI, van der Knaap MS. Imaging Patterns Characterizing Mitochondrial Leukodystrophies. AJNR Am J Neuroradiol. 2021 Jul;42(7):1334-1340. doi: 10.3174/ajnr.A7097. Epub 2021 Apr 1.
PubMed 34255734Kevelam SH, Steenweg ME, Srivastava S, Helman G, Naidu S, Schiffmann R, Blaser S, Vanderver A, Wolf NI, van der Knaap MS. Update on Leukodystrophies: A Historical Perspective and Adapted Definition. Neuropediatrics. 2016 Dec;47(6):349-354. doi: 10.1055/s-0036-1588020. Epub 2016 Aug 26.
PubMed 27564080Hosseinpour S, Razmara E, Heidari M, Rezaei Z, Ashrafi MR, Dehnavi AZ, Kameli R, Bereshneh AH, Vahidnezhad H, Azizimalamiri R, Zamani Z, Pak N, Rasulinezhad M, Mohammadi B, Ghabeli H, Ghafouri M, Mohammadi M, Zamani GR, Badv RS, Saket S, Rabbani B, Mahdieh N, Ahani A, Garshasbi M, Tavasoli AR. A comprehensive study of mutation and phenotypic heterogeneity of childhood mitochondrial leukodystrophies. Brain Dev. 2024 Apr;46(4):167-179. doi: 10.1016/j.braindev.2023.12.003. Epub 2023 Dec 21.
PubMed 38129218Finsterer J, Zarrouk Mahjoub S. Leukoencephalopathies in mitochondrial disorders: clinical and MRI findings. J Neuroimaging. 2012 Jul;22(3):e1-11. doi: 10.1111/j.1552-6569.2011.00693.x. Epub 2012 Feb 3.
PubMed 22303997Bindu PS, Sonam K, Chiplunkar S, Govindaraj P, Nagappa M, Vekhande CC, Aravinda HR, Ponmalar JJ, Mahadevan A, Gayathri N, Bharath MS, Sinha S, Taly AB. Mitochondrial leukoencephalopathies: A border zone between acquired and inherited white matter disorders in children? Mult Scler Relat Disord. 2018 Feb;20:84-92. doi: 10.1016/j.msard.2018.01.003. Epub 2018 Jan 6.
PubMed 29353736
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History and Genotype-Phenotype Correlations in Mitochondrial Leukoencephalopathies: A Multicentric, International Observational Study
- ClinicalTrials.gov ID
- NCT07868796
- Acronym / sponsor ID
- Leuko Mito / Leuko Mito
- Conditions
- Mitochondrial, Leukoencephalopathies, Leukoencephalopathy
- Keywords
- Mitochondrial disorder, leukoencephalopathy, leukodystrophy, mitochondrial leukoencephalopathy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
- Study start
- 15 Sep 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 9 Oct 2026 (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 disorders (MDs) are among the most common inherited metabolic diseases, caused by genetic defects in mitochondrial or nuclear DNA that impair cellular energy production. The central nervous system (CNS) is frequently affected, due to its high energy demands. Within the broad clinical spectrum of MDs, mitochondrial leukoencephalopathies (MLs) have emerged as a distinct subgroup characterized by CNS white matter involvement.
MLs are clinically and genetically heterogeneous, with onset ranging from infancy to adulthood. Patients may experience episodes of neurological regression, often triggered by stressors such as febrile illnesses, alongside variable motor, cognitive, and occasionally extraneurological involvement. Neuroimaging typically reveals diffuse or focal white matter abnormalities, including cavitation and rarefaction, with additional involvement of deep gray matter structures. Certain ML subtypes exhibit characteristic MRI patterns that may aid in diagnosis.
Despite recent advancements in the genetic and neuroradiological characterization of MLs, significant knowledge gaps persist. Although the number of disease-causing genes has increased over the last decades, a comprehensive understanding of genotype-phenotype correlations is still lacking. Additionally, knowledge on the natural history of these disorders is limited. Existing data often focus on imaging findings with insufficient integration of clinical, biochemical, and molecular features, limiting the understanding of disease mechanisms, progression, and therapeutic responses.
In light of these gaps, this multicenter, observational, retrospective study aims to systematically collect and analyze clinical, biochemical, neuroradiological, and genetic data from individuals with MLs, assessed at international reference centers for MDs. The study seeks to better elucidate the phenotypic variability and genotype-phenotype correlations of MLs. This work is expected to enhance diagnostic accuracy, inform management strategies, support prognostic counseling, and ultimately contribute to the better overall management of affected individuals
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patient with a confirmed genetic diagnosis of mitochondrial leukoencephalopathy
Key inclusion criteria (5 listed)
- Confirmed diagnosis of ML, confirmed by:
- Availability of clinical data, including medical records detailing symptom onset, disease progression, neuroimaging findings, and clinical management.
- Written informed consent obtained from the patient or their legal guardian (for minors or individuals with cognitive impairment). If the patient is deceased, consent for the use of medical records in this study will be obtained from the legally authorized representative or next of kin
Key exclusion criteria (6 listed)
- Unconfirmed diagnosis of mitochondrial leukoencephalopathy , including cases where:
- Insufficient clinical data, including cases where medical records lack essential information on symptom onset, disease progression, neuroimaging findings, or clinical management, preventing a meaningful contribution to the study's objectives.
- Concomitant diagnosis of another genetic disorder that may independently contribute to white matter abnormalities or neurological symptoms, confounding the assessment of ML progression and clinical outcomes
- Unavailability of written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Comprehensive characterization of genotype-phenotype correlations in MLs.
Time frame: 12 months
The primary endpoint for evaluating the principal objective of this study is the comprehensive characterization of genotype-phenotype correlations in MLs. This will be assessed through the collection and analysis of retrospective longitudinal clinical, neuroradiological and genetic data. Clinical phenotypes will then be stratified based on specific underlying genetic defects, assessing their impact on disease onset and progression to establish robust genotype-phenotype correlations. Data collection will include: * Family history, including inheritance patterns and consanguinity when applicable. * Age at symptom onset * Initial clinical presentation, documenting key symptoms and signs at disease onset. * Progression of disease manifestations, capturing the evolution of neurological and extraneurological features over time. * Neuroradiological findings, assessed through MRI scans to evaluate white matter abnormalities, other signal abnormalities or specific MRI findings
8 secondary outcomes
The comprehensive characterization of disease progression in MLs, assessed through the collection and analysis of longitudinal clinical, instrumental and genetic data: NMDAS
Time frame: 12 months
The comprehensive characterization of disease progression in MLs, assessed through the collection and analysis of longitudinal clinical, instrumental and genetic data: Serum lactate levels
Time frame: 12 months
The comprehensive characterization of disease progression in MLs, assessed through the collection and analysis of longitudinal clinical, instrumental and genetic data. : Serum pyruvate levels
Time frame: 12 months
Change in disease severity in treated adult participants assessed by NMDAS
Time frame: 12 months
Change in disease severity in treated pediatric participants assessed by NPMDS
Time frame: 12 months
Change in serum lactate levels in treated participants
Time frame: 12 months
Change in serum pyruvate levels in treated participants
Time frame: 12 months
Progression of brain MRI abnormalities in treated participants
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Background: PubMed 34255734Roosendaal SD, van de Brug T, Alves CAPF, Blaser S, Vanderver A, Wolf NI, van der Knaap MS. Imaging Patterns Characterizing Mitochondrial Leukodystrophies. AJNR Am J Neuroradiol. 2021 Jul;42(7):1334-1340. doi: 10.3174/ajnr.A7097. Epub 2021 Apr 1.
- Background: PubMed 27564080Kevelam SH, Steenweg ME, Srivastava S, Helman G, Naidu S, Schiffmann R, Blaser S, Vanderver A, Wolf NI, van der Knaap MS. Update on Leukodystrophies: A Historical Perspective and Adapted Definition. Neuropediatrics. 2016 Dec;47(6):349-354. doi: 10.1055/s-0036-1588020. Epub 2016 Aug 26.
- Background: PubMed 38129218Hosseinpour S, Razmara E, Heidari M, Rezaei Z, Ashrafi MR, Dehnavi AZ, Kameli R, Bereshneh AH, Vahidnezhad H, Azizimalamiri R, Zamani Z, Pak N, Rasulinezhad M, Mohammadi B, Ghabeli H, Ghafouri M, Mohammadi M, Zamani GR, Badv RS, Saket S, Rabbani B, Mahdieh N, Ahani A, Garshasbi M, Tavasoli AR. A comprehensive study of mutation and phenotypic heterogeneity of childhood mitochondrial leukodystrophies. Brain Dev. 2024 Apr;46(4):167-179. doi: 10.1016/j.braindev.2023.12.003. Epub 2023 Dec 21.
- Background: PubMed 22303997Finsterer J, Zarrouk Mahjoub S. Leukoencephalopathies in mitochondrial disorders: clinical and MRI findings. J Neuroimaging. 2012 Jul;22(3):e1-11. doi: 10.1111/j.1552-6569.2011.00693.x. Epub 2012 Feb 3.
- Background: PubMed 29353736Bindu PS, Sonam K, Chiplunkar S, Govindaraj P, Nagappa M, Vekhande CC, Aravinda HR, Ponmalar JJ, Mahadevan A, Gayathri N, Bharath MS, Sinha S, Taly AB. Mitochondrial leukoencephalopathies: A border zone between acquired and inherited white matter disorders in children? Mult Scler Relat Disord. 2018 Feb;20:84-92. doi: 10.1016/j.msard.2018.01.003. Epub 2018 Jan 6.
- 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.
Anna Ardissone, MD principal investigator
Fondazione IRCCS Istituto Neurologico Carlo Besta
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 and Leukoencephalopathies, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 1 site in Italy.
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 5 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 9 Oct 2026. 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 Italy. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna Ardissone, MD (+ 39 02.2394, anna.ardissone@istituto-besta.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comprehensive characterization of genotype-phenotype correlations in MLs. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07868796, which also lists 5 linked publications.
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 9 Oct 2026.