Clinical trial NCT05250375: Mitochondrial Myopathy Rating Scale
Official title: Development and Validation of a Myopathy Rating Scale in Mitochondrial Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Mitochondrial Disease
Keywords: Mitochondrial Myopathy
Mitochondrial Disease
Healthy Volunteers
Natural History
Muscle Weakness
Fatigue
Outcome Measures
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
name: United Mitochondrial Disease Foundation (UMDF)
name: National Institutes of Health (NIH)
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2022-02-22
Enrollment: 1300
Sex: ALL
Minimum age (years): 0
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with primary mitochondrial myopathy and healthy volunteers

Brief summary: The goal of this observational study is to develop and validate tools to measure disease course in patients with primary mitochondrial myopathy (PMM). The main aims of this study are:

* Development, validation, and optimization of objective outcome measures for mitochondrial myopathy
* Defining the natural history of mitochondrial myopathy

Researchers will compare data from patients with primary mitochondrial myopathy to healthy controls. Data from healthy controls will also help define normative data for future studies.

Participants will perform clinical exams of muscle strength and endurance and will complete surveys.

Detailed description: Currently, natural history knowledge is limited for all PMM. The clinical phenotype and disease course may be distinct depending on the PMM genetic etiology, however variability between family members harboring the same genetic mutation is also well described.

A major barrier to precise documentation of clinical progression has been the absence of meaningful and validated PMM-specific outcome measures. The long-term goal of these cumulative studies is to promote robust PMM clinical trial design and drug approval, as facilitated by natural history data and validation of PMM-specific objective outcome measures that enable accurate quantitation of symptoms. The overarching hypothesis is that deeper understanding of mitochondrial myopathy will promote meaningful clinical trial design. This study is approved under Children's Hospital of Philadelphia (CHOP), Institutional Review Board (IRB) protocol (#16-013364, PI Zolkipli) and is supported by a research infrastructure that includes physical therapists, biostatistician and bioinformatician for automated clinical data extraction from medical records.

Eligibility criteria: MM Cohort Inclusion Criteria

1. Males or females age 0-100 years of age
2. Mitochondrial disorder established by confirmed genetic or biochemical mutation in mtDNA or nuclear DNA OR is suitable for participation in the opinion of the investigator based on clinical presentation.
3. Exhibits myopathy (exercise intolerance, muscle strength, fatigue) relating to Mitochondrial disease in the opinion of the investigator
4. Able to provide written consent OR parental permission and child assent OR if they are an adult with diminished capacity, an LAR or healthcare representative is able to and willing to provide consent ., as approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)

MM Cohort Exclusion Criteria

1. Male or female fetuses
2. Non English speakers
3. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
4. Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations of these criteria must be reported in accordance with IRB Policies and Procedures.

Healthy Control Cohort Inclusion Criteria

1. Males or females age 0-100 years of age
2. No history of mitochondrial myopathy symptoms
3. Able to provide written consent or parental permission and child assent., approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)
4. Individual is not a study staff member or a family member of a study staff member (not listed as a study staff in eIRB)

Healthy Control Exclusion Criteria

1. Male or female fetuses
2. Non English speakers
3. Mitochondrial disorder established by confirmed genetic or biochemical mutation in mtDNA or nuclear DNA
4. Exhibits myopathy (exercise intolerance, muscle strength, fatigue) relating to Mitochondrial disease
5. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
6. Individual is listed as a study staff member in eIRB, OR individual is a family member of a study staff member listed in eIRB
7. Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations of these criteria must be reported in accordance with IRB Policies and Procedures.

Primary outcomes:
measure: Muscle Strength of MM-COAST
timeFrame: through study completion, an average of 5 years
measure: Balance of the MM-COAST
timeFrame: through study completion, an average of 5 years
measure: Dexterity of the MM-COAST
timeFrame: through study completion, an average of 5 years
measure: Mitochondrial Disease Burden for Adults
timeFrame: through study completion, an average of 5 years
measure: Mitochondrial Disease Burden for Children
timeFrame: through study completion, an average of 5 years
measure: Challenges in Activities of Daily Life (ADLs)
timeFrame: through study completion, an average of 5 years
measure: Functional Tasks of the Mitochondrial Myopathy Functional Scale (MMFS)
timeFrame: through study completion, an average of 5 years
measure: Clinical Progression: Survival
timeFrame: through study completion, an average of 5 years
measure: Clinical Progression: Growth
timeFrame: through study completion, an average of 5 years
measure: Clinical Progression: Other Illnesses
timeFrame: through study completion, an average of 5 years
measure: Clinical Progression: Hospitalizations
timeFrame: through study completion, an average of 5 years
measure: Clinical Progression: Ambulatory Status
timeFrame: through study completion, an average of 5 years
measure: Clinical Progression: Pacemaker Requirement
timeFrame: through study completion, an average of 5 years
measure: Clinical Progression: Ventilatory Support
timeFrame: through study completion, an average of 5 years
measure: Clinical Progression: Gastrostomy Status
timeFrame: through study completion, an average of 5 years
measure: Qualitative Interviews
timeFrame: through study completion, an average of 5 years
measure: MM patient-reported outcome measure (PROM), MM-IMPACT
timeFrame: through study completion, an average of 5 years
Secondary outcomes:
measure: Cerebellar Ataxia Outcome Measure for Primary Mitochondrial Disease (PMD)
timeFrame: through study completion, an average of 5 years
measure: Clinical Meaningfulness of Ataxia Quantification.
timeFrame: through study completion, an average of 5 years
measure: Evaluation of Health-Related Quality of Life by PedsQL
timeFrame: through study completion, an average of 5 years
measure: Evaluation of daily functional activities by PEDI-CAT
timeFrame: through study completion, an average of 5 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Zarazuela Zolkipli-Cunningham, MBChB
role: PRINCIPAL_INVESTIGATOR
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