An observational study in Primary Mitochondrial Disease, sponsored by Children's Hospital of Philadelphia. Recruiting at 1 site in United States. Open to participants aged 0 Years to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-17.
Sponsored by Children's Hospital of Philadelphia · Observational
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:
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.
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.
46 studies on the registry are indexed under Mitochondrial Myopathies; 14 are open to participants now.
This study's planned enrollment of 1,300 is above the median of 42 across 15 observational studies indexed under Mitochondrial Myopathies.
Browse Mitochondrial Myopathies studies →Children's Hospital of Philadelphia is the lead sponsor of 489 studies on the registry; 90 are open to participants now.
Of its 28 completed or terminated interventional studies of FDA-regulated products, 22 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Individuals with primary mitochondrial myopathy and healthy volunteers
MM Cohort Inclusion Criteria
MM Cohort Exclusion Criteria
Healthy Control Cohort Inclusion Criteria
Healthy Control Exclusion Criteria
Patients with a 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 and exhibits myopathy (exercise intolerance, muscle strength, fatigue) relating to mitochondrial disease.
Males or females age 0-100 years of age with no history of mitochondrial myopathy symptoms.
Muscle Strength of MM-COAST
Muscle strength will be measured longitudinally by handheld dynamometry strength assessments to confirm muscle weakness in proximal and distal muscle groups.
Time frame: through study completion, an average of 5 years
Balance of the MM-COAST
Balance will be measured by: (1) Standing tandem with eyes closed, (2) Standing tandem with eyes open, and (3) Single leg stand with eyes closed tests.
Time frame: through study completion, an average of 5 years
Dexterity of the MM-COAST
Dexterity will be measured by 9 Hole Peg Test (9HPT) and Functional Dexterity Test (FDT).
Time frame: through study completion, an average of 5 years
Mitochondrial Disease Burden for Adults
All subjects will complete the 'gold standard' Newcastle Scale of disease burden. Newcastle Adult Scale (NMDAS): Each question in the NMDAS has a possible score from 0-5. Each of the first 3 section scores are calculated by simply summing the scores obtained for each question in that section. The higher the score the more severe the disease. The quality of life section has separate scoring.
Time frame: through study completion, an average of 5 years
Mitochondrial Disease Burden for Children
All subjects and their parents will complete the 'gold standard' Newcastle Scale of disease burden. Newcastle Pediatric Scale (NPMDS): NPMDS is scored by section and the final (total) score is the sum of all section scores. The section scores vary by age group (0-24 months, 2-11 years, and 12-18 years). Maximum possible total NPMDS scores are 95 for subjects under 24 months of age and 107 for those between two and 18 years of age. Higher scores indicate worse conditions.
Time frame: through study completion, an average of 5 years
Challenges in Activities of Daily Life (ADLs)
All subjects and their parents will complete the Karnofsky-Lansky score to assess functional abilities at each visit. Karnofsky Lansky Scale: 0-100. 0-40: Unable to care for self, requires equivalent of institutional or hospital care; disease may be progressing rapidly. 50-70: Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed. 80-100: Able to carry on normal activity and to work; no special care needed.
Time frame: through study completion, an average of 5 years
Functional Tasks of the Mitochondrial Myopathy Functional Scale (MMFS)
The MMFS (In Person and Telemedicine Versions) will be used to quantify motor performance in NUBPL-disease in abilities to complete functional tasks such as standing, walking and gait. MMFS data will be correlated using Pearson correlation coefficient to Newcastle and Karnofsky scores, and objective measures to assess for clinical meaning. MMFS Scale: 3: Able (fully meets criteria); 2: Moderately Able (partially meets, some compensation needed); 1: Minimally Able (significant compensation needed); 0: Unable MMFS Totals: In-person Version: Total score: \*/ 66 (max score), Telemedicine Version: Total score: \*/54 (max score)
Time frame: through study completion, an average of 5 years
Clinical Progression: Survival
Patients will be marked as either "alive" or "deceased" at the time of a given visit date.
Time frame: through study completion, an average of 5 years
Clinical Progression: Growth
Patients will have their vitals recorded at the date of visit to obtain BMI (Kg/m\^2)) measurement, Height (m) and weight (kg) are required to calculate BMI.
Time frame: through study completion, an average of 5 years
Clinical Progression: Other Illnesses
Patients will have other illnesses not related to their mitochondrial disease recorded along with date of diagnosis and stability.
Time frame: through study completion, an average of 5 years
Clinical Progression: Hospitalizations
Patients will have prior hospitalizations counted and recorded. Any hospitalizations occurring within a year from the visit date will have specific information recorded including the dates of admission and discharge, and the reasons for admission and discharge.
Time frame: through study completion, an average of 5 years
Clinical Progression: Ambulatory Status
Patients will have their ambulatory status assessed by recording whether or not they can take 5 steps on their own. Patients' use of different kinds of wheelchairs will be recorded (manual, power assist, or power wheelchair or scooter) along with whether they are able to ambulate in the community or only in the household.
Time frame: through study completion, an average of 5 years
Clinical Progression: Pacemaker Requirement
As part of a patient's cardiopulmonary exercise test (CPET), pacemaker status will be assessed, and if a patient utilizes a pacemaker, it's make, model, and settings will be recorded.
Time frame: through study completion, an average of 5 years
Clinical Progression: Ventilatory Support
As part of a patient's respiratory history, ventilatory support status will be assessed by recording whether a patient uses the any of the following respiratory equipment: cough assist device, non-invasive ventilation including continuous positive airway pressure (CPAP) and Bi-pap, chest percussion, suctioning devices, other ventilation devices.
Time frame: through study completion, an average of 5 years
Clinical Progression: Gastrostomy Status
As part of a patient's nutritional assessment, a patient's gastrostomy status will be assessed by determining whether a patient utilizes a gastrostomy tube (or g-tube), when they had their g-tube placed and why, and whether it resulted in weight gain.
Time frame: through study completion, an average of 5 years
Qualitative Interviews
In-depth qualitative interviews to assess their perspective of meaningful change of individual domain assessments of the MM-COAST and MM-Function Scale.
Time frame: through study completion, an average of 5 years
MM patient-reported outcome measure (PROM), MM-IMPACT
Preliminary MM-IMPACT PROM, a multi-item scale which currently consists of 45 questions
Time frame: through study completion, an average of 5 years
Cerebellar Ataxia Outcome Measure for Primary Mitochondrial Disease (PMD)
Investigators will utilize a similar approach to development of the MM-COAST and MMFS and systematically collate and administer existing ataxia scales, focusing on quantitation of cerebellar ataxia, dysarthria and tremor, and introduce modifications to ensure PMD-specificity of this outcome measure. Once developed, investigators will administer the devised ataxia scale to the NUBPL subjects at every clinic visit, where the time to completion and modifications needed are assessed. Further iterations of the ataxia scale will be re-assessed in the NUBPL-subjects at every clinic visit and compared to the performance of the scale in PMD patients with other genetic etiologies. Participants will be instructed to refrain from strenuous exercise 24 hours prior to each visit. Feasibility and testing reproducibility of the PMD-ataxia scale will be evaluated at 2 different time points. The ataxia scale will be developed in months 0-6 and administered in months 6-12 of the 1-year project period.
Time frame: through study completion, an average of 5 years
Clinical Meaningfulness of Ataxia Quantification.
All subjects will complete the following patient/parent-reported surveys: Newcastle Adult Scale (NMDAS) has 3 section scores that are calculated by summing the scores of each question (0-5). The Newcastle Quality of Life (Section IV) has separate scoring. Newcastle Pediatric Scale (NPMDS) is scored by section(scores vary by age group) and the final (total) score is the sum of all section scores. The maximum possible total NPMDS scores are 95 for subjects under 24 months of age and 107 for those 2-18 years of age. In both, higher scores indicate worse conditions. Karnofsky Lansky Scale is scaled 0-100. 0-40: unable to care for self, 50-70: unable to work; able to live at home, care for most personal needs, 80-100: Able to carry on normal activity and work; no special care needed. To assess if the quantified ataxia scores will be clinically meaningful: correlation to the 'gold standard' Newcastle Scale of disease severity and MM-COAST objective assessments in Aim 1 will be assessed.
Time frame: through study completion, an average of 5 years
Evaluation of Health-Related Quality of Life by PedsQL
PedsQL is a 23-item questionnaire that evaluates health-related quality of life that is reported as a total score and 3 summary scores that include Physical Health, Psychosocial Health and School/Work with a higher score indicating better quality of life. The range for the scores are 0-100.
Time frame: through study completion, an average of 5 years
Evaluation of daily functional activities by PEDI-CAT
The Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) is a test that evaluates daily functional activities. A t-score of 50 represents the function of the general population (SD of 10). A t-score below 30 reflects poor performance compared to the general population. The range for the scores are 20-80.
Time frame: through study completion, an average of 5 years
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