AzTrials
AzTrials

Primary Mitochondrial DiseaseNCT05250375

Natural History Study of Mitochondrial Myopathy

An observational study of Primary Mitochondrial Disease, run by Children's Hospital of Philadelphia at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 0 to 100 yearsHealthy volunteers can take part
Conditions the study is for
Primary Mitochondrial Disease
How many people
1,300 participants
Where
1 siteUnited States
Study dates
24 Mar 2017to 24 Mar 2030
How long will I take part?
20 Years
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 0 to 100 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Study population: Individuals with primary mitochondrial myopathy and healthy volunteers

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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Katelynn Stanley, BS contact

267 426 4961

MitochondrialMyopathyResearch@chop.edu

Jean Flickinger, PT contact

267 426 4961

MitochondrialMyopathyResearch@chop.edu

United States1 site, 1 recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Amanda Wellik, 267-426-4961, MitochondrialMyopathyResearch@chop.edu

    Recruiting

Other trials in United States

About this study

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.

Read the 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.

Keywords
Mitochondrial Myopathy, Mitochondrial Disease, Healthy Volunteers, Natural History, Muscle Weakness, Fatigue, Outcome Measures
Medical subject headings
Mitochondrial Myopathies, Mitochondrial Diseases, Muscle Weakness, Fatigue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT05250375
Study groupRoleWhat they receive
Primary Mitochondrial MyopathyPatients 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.
Healthy ControlsMales or females age 0-100 years of age with no history of mitochondrial myopathy symptoms.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: through study completion, an average of 5 years

  2. 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.

    Measured: through study completion, an average of 5 years

  3. Dexterity of the MM-COAST

    Dexterity will be measured by 9 Hole Peg Test (9HPT) and Functional Dexterity Test (FDT).

    Measured: through study completion, an average of 5 years

  4. 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.

    Measured: through study completion, an average of 5 years

  5. 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.

    Measured: through study completion, an average of 5 years

  6. 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.

    Measured: through study completion, an average of 5 years

  7. 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)

    Measured: through study completion, an average of 5 years

  8. Clinical Progression: Survival

    Patients will be marked as either "alive" or "deceased" at the time of a given visit date.

    Measured: through study completion, an average of 5 years

  9. 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.

    Measured: through study completion, an average of 5 years

  10. Clinical Progression: Other Illnesses

    Patients will have other illnesses not related to their mitochondrial disease recorded along with date of diagnosis and stability.

    Measured: through study completion, an average of 5 years

  11. 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.

    Measured: through study completion, an average of 5 years

  12. 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.

    Measured: through study completion, an average of 5 years

  13. 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.

    Measured: through study completion, an average of 5 years

  14. 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.

    Measured: through study completion, an average of 5 years

  15. 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.

    Measured: through study completion, an average of 5 years

  16. 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.

    Measured: through study completion, an average of 5 years

  17. MM patient-reported outcome measure (PROM), MM-IMPACT

    Preliminary MM-IMPACT PROM, a multi-item scale which currently consists of 45 questions

    Measured: through study completion, an average of 5 years

Secondary outcomes (4)

  1. 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.

    Measured: through study completion, an average of 5 years

  2. 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.

    Measured: through study completion, an average of 5 years

  3. 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.

    Measured: through study completion, an average of 5 years

  4. 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.

    Measured: through study completion, an average of 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2022
  2. Study start24 Mar 2017
  3. Primary completion24 Mar 2030 (estimated)
  4. Study completion24 Mar 2030 (estimated)

Resources

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
Prospective
Enrolment
1,300 participants (estimated)
Target duration
20 Years
IDs, dates and publications
ClinicalTrials.gov ID
NCT05250375
Sponsor's protocol ID
16-013364
Other IDs
1R01AR083552-01A1
Status last verified
Sep 2026
First submitted
6 Aug 2021
Last updated
17 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • McKay MJ, Cartwright J, Ferreira P, Simic M, Vanicek N, Hiller CE, Nightingale EJ, Moloney NA, Quinlan KG, Pourkazemi F, Sman AD, Nicholson LL, Mousavi SJ, Rose K, Raymond J, Mackey MG, Chard A, Hubscher M, Wegener C, Fong Yan A, Refshauge KM, Burns J; 1000 Norms Project Consortium. 1000 Norms Project: protocol of a cross-sectional study cataloging human variation. Physiotherapy. 2016 Mar;102(1):50-56. doi: 10.1016/j.physio.2014.12.002. Epub 2015 Jan 22.

    PubMed 25733400

  • Burstein DS, McBride MG, Min J, Paridon AA, Perelman S, Huffman EM, O'Malley S, Del Grosso J, Groepenhoff H, Paridon SM, Brothers JA. Normative Values for Cardiopulmonary Exercise Stress Testing Using Ramp Cycle Ergometry in Children and Adolescents. J Pediatr. 2021 Feb;229:61-69.e5. doi: 10.1016/j.jpeds.2020.09.018. Epub 2020 Sep 11.

    PubMed 32926876

  • DeBrosse C, Nanga RPR, Wilson N, D'Aquilla K, Elliott M, Hariharan H, Yan F, Wade K, Nguyen S, Worsley D, Parris-Skeete C, McCormick E, Xiao R, Cunningham ZZ, Fishbein L, Nathanson KL, Lynch DR, Stallings VA, Yudkoff M, Falk MJ, Reddy R, McCormack SE. Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders. JCI Insight. 2016 Nov 3;1(18):e88207. doi: 10.1172/jci.insight.88207.

    PubMed 27812541

  • Schaefer AM, Phoenix C, Elson JL, McFarland R, Chinnery PF, Turnbull DM. Mitochondrial disease in adults: a scale to monitor progression and treatment. Neurology. 2006 Jun 27;66(12):1932-4. doi: 10.1212/01.wnl.0000219759.72195.41.

    PubMed 16801664

  • Phoenix C, Schaefer AM, Elson JL, Morava E, Bugiani M, Uziel G, Smeitink JA, Turnbull DM, McFarland R. A scale to monitor progression and treatment of mitochondrial disease in children. Neuromuscul Disord. 2006 Dec;16(12):814-20. doi: 10.1016/j.nmd.2006.08.006. Epub 2006 Nov 22.

    PubMed 17123819

  • Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, Battista V, Koenigsberger DY, Pascual JM, Shanske S, Sano M, Mao X, Hirano M, Shungu DC, Dimauro S, De Vivo DC. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology. 2011 Nov 29;77(22):1965-71. doi: 10.1212/WNL.0b013e31823a0c7f. Epub 2011 Nov 16.

    PubMed 22094475

  • Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, Taylor RW, Turnbull DM, McFarland R. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015 May;77(5):753-9. doi: 10.1002/ana.24362. Epub 2015 Mar 28.

    PubMed 25652200

  • Rahman J, Rahman S. Mitochondrial medicine in the omics era. Lancet. 2018 Jun 23;391(10139):2560-2574. doi: 10.1016/S0140-6736(18)30727-X. Epub 2018 Jun 18.

    PubMed 29903433

  • Friederich MW, Perez FA, Knight KM, Van Hove RA, Yang SP, Saneto RP, Van Hove JLK. Pathogenic variants in NUBPL result in failure to assemble the matrix arm of complex I and cause a complex leukoencephalopathy with thalamic involvement. Mol Genet Metab. 2020 Mar;129(3):236-242. doi: 10.1016/j.ymgme.2019.12.013. Epub 2019 Dec 30.

    PubMed 31917109

  • Kimonis V, Al Dubaisi R, Maclean AE, Hall K, Weiss L, Stover AE, Schwartz PH, Berg B, Cheng C, Parikh S, Conner BR, Wu S, Hasso AN, Scott DA, Koenig MK, Karam R, Tang S, Smith M, Chao E, Balk J, Hatchwell E, Eis PS. NUBPL mitochondrial disease: new patients and review of the genetic and clinical spectrum. J Med Genet. 2021 May;58(5):314-325. doi: 10.1136/jmedgenet-2020-106846. Epub 2020 Jun 9.

    PubMed 32518176

  • Glanzman AM, Mazzone ES, Young SD, Gee R, Rose K, Mayhew A, Nelson L, Yun C, Alexander K, Darras BT, Zolkipli-Cunningham Z, Tennekoon G, Day JW, Finkel RS, Mercuri E, De Vivo DC, Baldwin R, Bishop KM, Montes J. Evaluator Training and Reliability for SMA Global Nusinersen Trials1. J Neuromuscul Dis. 2018;5(2):159-166. doi: 10.3233/JND-180301.

    PubMed 29865090

  • Campolina-Sampaio GP, Lasmar LM, Ribeiro BS, Giannetti JG. The Newcastle Pediatric Mitochondrial Disease Scale: translation and cultural adaptation for use in Brazil. Arq Neuropsiquiatr. 2016 Nov;74(11):909-913. doi: 10.1590/0004-282X20160137.

    PubMed 27901256

  • MANUAL FOR NEWCASTLE MITOCHONDRIAL DISEASE ADULT SCALE (NMDAS). Wellcome Trust Centre Mitochondrial Research.

Questions about this trial

What is this clinical trial studying?

An observational study of Primary Mitochondrial Disease, run by Children's Hospital of Philadelphia at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 17 Sep 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 United States. 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 Katelynn Stanley, BS (267 426 4961, MitochondrialMyopathyResearch@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Muscle Strength of MM-COAST (time frame: through study completion, an average of 5 years). The study lists 17 primary outcomes in all. 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 NCT05250375, which also lists 13 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 17 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in