Ignite Creation Date:
2024-10-25 @ 8:02 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06504433
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-11
Brief Title:
The Natural History of Mitochondrial Diseases
Sponsor:
None
Organization:
None
Study Overview
Official Title:
The Natural History of Mitochondrial Diseases
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 sexesgenders over 18 years of age and healthy volunteers The main questions 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 Parkinsons disease andor 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
The goal of this observational study non-randomised retrospective and prospective is to fully characterise primary MITO disease that includes both sexesgenders over 18 years of age and healthy volunteers The main questions 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 Parkinsons disease andor 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
Detailed Description:
Primary Mitochondrial Disease MITO is a serious and debilitating condition often multi-systemic and requiring life-long monitoring and treatment of symptoms to reduce the risk of life-threatening episodes metabolic crises or acute illness Although rare MITO is the most common group of inherited metabolic diseases and is associated with abnormalities of the mitochondrial respiratory chain which carries out oxidative phosphorylation to produce ATP Gorman et al 2016
In adults MITO is often a progressive multisystem disorder with frequent long-term monitoring and symptom management required to reduce the risk of an acute illness andor other life-threatening episodes and metabolic crises
Given that mtDNA mutations are typically transmitted through the maternal line paternally related family members are not at risk and will represent asymptomatic controls In sporadic cases such as chronic progressive external ophthalmoplegia CPEO that are typically caused by sporadic mtDNA deletions family members are not at risk of carrying the disorder and thus can act as family member controls Similarly those family members of participants with a nuclear DNA mutation such as autosomal dominant mitochondrial disease eg OPA1 gene and who do not carry the affected gene are also suitable asymptomatic controls
This study will establish the AMDC Clinical Registry at NeuRA Patients with confirmed MITO the presence of pathogenic nuclear or mitochondrial DNA variantsdeletion and control participants that can include biological relatives of MITO participants with no clinical disease and no genetic risk participants with a clinically confirmed non-MITO neurologic disorder or age and gender-matched healthy controls followed over at least 120 months 10 years
Study data will include detailed medical and social history summary of clinical presentation and clinical social history collected through diaries or on clinical review neurological examination findings results of investigations performed as standard of care including laboratory findings through blood tests imaging studies cardiac investigations gastrointestinal transit studies neurophysiological studies and analysis of archived muscle andor skin biopsies
Individuals of any age with confirmed MITO that requires the presence of pathogenic nuclear or mitochondrial DNA variantsdeletion Control participants 100 may fall into one of three categories asymptomatic relatives of confirmed MITO patients those with no genetic risk patients with clinically confirmed non-MITO neurological disorders or age and gender-matched healthy controls
If genetic mutations are not demonstrated MITO can be diagnosed using clinical diagnostic criteria including the Walker Criteria or the Nijmegen criteria consensus mitochondrial disease criteria scoring system
All patients must agree to participate in the Australian Mitochondrial Disease Centre AMDC Clinical Registry and donate at a minimum a blood sample for the prospective biobank for the collection and storage of biological samples for future use
Overall individual disease courses in MITO range from slow to more rapid progressive decline to stepwise deterioration often attributable to metabolic events eventuating as a potentially fatal disease To further complicate these already immense diagnostic and prognostic challenges external or environmental factors such as toxins inflammation nutrition the microbiome and the natural aging process are now being postulated to additionally influence the onset organ involvement severity and progression of disease although this is poorly understood
MITO is a vastly heterogeneous disease and a genetic diagnosis does not necessarily nor comprehensively inform the clinician how the disease will manifest clinically in an individual A deeper understanding of MITOs natural history and its associated biomarkers will instead provide the clinician with the necessary tools and a greater understanding that optimises patient care Additionally it will allow for more accurate
screening of patients and when to apply mitochondrial genomic testing
prediction of disease severity and prognosis
matching of clinical presentations to genotypes
monitoring for symptomatic and metabolic changes to minimiseprevent potential crises
utilisation of appropriate management plans their effectiveness assessment
application of available targeted treatments and clinical trials and
application of preventative strategies such as mitochondrial donation techniques
By collecting the clinically relevant data of each genetically diagnosed patient the study will map and identify factors that influence disease to assist not only current NeuRA clinicians but future clinicians in the management of MITO patients Biospecimens will be collected to form the Australian Mitochondrial Disease Centre AMCD biobank that will facilitate separate and future biomarker discovery research important for the assessment of organ involvement disease severity and responses to therapies With the benefits of earlier diagnoses improved patient care and health outcomes and aiding drugtreatment discovery
In this longitudinal study we aim to further define existing and identify the different MITO phenotypes examine possible associations between specific events in the medical history of the patient identify correlations between the signs and symptoms of MITO presentations and disease severity prognostic indicators and survival and create an informative biobank One that can be accessed for future use in ethically approved protocols and where biospecimens can be reassessed to identify precise mitochondrial biomarkers that aid a timelier MITO diagnosis or prediction of disease progression Clinical symptoms will also be correlated with environmental factors such as medications and physical exercise to provide an improved understanding of how treatments lifestyle and dietary interventions impact the clinical course of MITO
Overall Aim To perform a longitudinal study of MITO over 10 years and create a clinical database to examine possible associations between clinical features disease phenotypes and disease progression in MITO participants and relevant controls Various biospecimens will be collected to form a biobank that will facilitate MITO biomarker research and that can be accessed using ethics-approved protocols for future research
Project outcomes This study will establish the AMDC Clinical Biobank repository Patients with MITO and their asymptomatic relatives with no genetic risk will be followed for at least 10 years with biospecimen collection to form a Biobank that will facilitate MITO biomarker research The data generated may identify triggers of clinical symptoms and associations between clinical and environmental parameters Future research studies using ethics-approved protocols to access biospecimens in the biobank will facilitate MITO biomarker research that would allow earlier diagnosis of MITO identify organ involvement track disease progression to help with prognostication and improve disease management
In adults MITO is often a progressive multisystem disorder with frequent long-term monitoring and symptom management required to reduce the risk of an acute illness andor other life-threatening episodes and metabolic crises
Given that mtDNA mutations are typically transmitted through the maternal line paternally related family members are not at risk and will represent asymptomatic controls In sporadic cases such as chronic progressive external ophthalmoplegia CPEO that are typically caused by sporadic mtDNA deletions family members are not at risk of carrying the disorder and thus can act as family member controls Similarly those family members of participants with a nuclear DNA mutation such as autosomal dominant mitochondrial disease eg OPA1 gene and who do not carry the affected gene are also suitable asymptomatic controls
This study will establish the AMDC Clinical Registry at NeuRA Patients with confirmed MITO the presence of pathogenic nuclear or mitochondrial DNA variantsdeletion and control participants that can include biological relatives of MITO participants with no clinical disease and no genetic risk participants with a clinically confirmed non-MITO neurologic disorder or age and gender-matched healthy controls followed over at least 120 months 10 years
Study data will include detailed medical and social history summary of clinical presentation and clinical social history collected through diaries or on clinical review neurological examination findings results of investigations performed as standard of care including laboratory findings through blood tests imaging studies cardiac investigations gastrointestinal transit studies neurophysiological studies and analysis of archived muscle andor skin biopsies
Individuals of any age with confirmed MITO that requires the presence of pathogenic nuclear or mitochondrial DNA variantsdeletion Control participants 100 may fall into one of three categories asymptomatic relatives of confirmed MITO patients those with no genetic risk patients with clinically confirmed non-MITO neurological disorders or age and gender-matched healthy controls
If genetic mutations are not demonstrated MITO can be diagnosed using clinical diagnostic criteria including the Walker Criteria or the Nijmegen criteria consensus mitochondrial disease criteria scoring system
All patients must agree to participate in the Australian Mitochondrial Disease Centre AMDC Clinical Registry and donate at a minimum a blood sample for the prospective biobank for the collection and storage of biological samples for future use
Overall individual disease courses in MITO range from slow to more rapid progressive decline to stepwise deterioration often attributable to metabolic events eventuating as a potentially fatal disease To further complicate these already immense diagnostic and prognostic challenges external or environmental factors such as toxins inflammation nutrition the microbiome and the natural aging process are now being postulated to additionally influence the onset organ involvement severity and progression of disease although this is poorly understood
MITO is a vastly heterogeneous disease and a genetic diagnosis does not necessarily nor comprehensively inform the clinician how the disease will manifest clinically in an individual A deeper understanding of MITOs natural history and its associated biomarkers will instead provide the clinician with the necessary tools and a greater understanding that optimises patient care Additionally it will allow for more accurate
screening of patients and when to apply mitochondrial genomic testing
prediction of disease severity and prognosis
matching of clinical presentations to genotypes
monitoring for symptomatic and metabolic changes to minimiseprevent potential crises
utilisation of appropriate management plans their effectiveness assessment
application of available targeted treatments and clinical trials and
application of preventative strategies such as mitochondrial donation techniques
By collecting the clinically relevant data of each genetically diagnosed patient the study will map and identify factors that influence disease to assist not only current NeuRA clinicians but future clinicians in the management of MITO patients Biospecimens will be collected to form the Australian Mitochondrial Disease Centre AMCD biobank that will facilitate separate and future biomarker discovery research important for the assessment of organ involvement disease severity and responses to therapies With the benefits of earlier diagnoses improved patient care and health outcomes and aiding drugtreatment discovery
In this longitudinal study we aim to further define existing and identify the different MITO phenotypes examine possible associations between specific events in the medical history of the patient identify correlations between the signs and symptoms of MITO presentations and disease severity prognostic indicators and survival and create an informative biobank One that can be accessed for future use in ethically approved protocols and where biospecimens can be reassessed to identify precise mitochondrial biomarkers that aid a timelier MITO diagnosis or prediction of disease progression Clinical symptoms will also be correlated with environmental factors such as medications and physical exercise to provide an improved understanding of how treatments lifestyle and dietary interventions impact the clinical course of MITO
Overall Aim To perform a longitudinal study of MITO over 10 years and create a clinical database to examine possible associations between clinical features disease phenotypes and disease progression in MITO participants and relevant controls Various biospecimens will be collected to form a biobank that will facilitate MITO biomarker research and that can be accessed using ethics-approved protocols for future research
Project outcomes This study will establish the AMDC Clinical Biobank repository Patients with MITO and their asymptomatic relatives with no genetic risk will be followed for at least 10 years with biospecimen collection to form a Biobank that will facilitate MITO biomarker research The data generated may identify triggers of clinical symptoms and associations between clinical and environmental parameters Future research studies using ethics-approved protocols to access biospecimens in the biobank will facilitate MITO biomarker research that would allow earlier diagnosis of MITO identify organ involvement track disease progression to help with prognostication and improve disease management
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None