Natural History Study of Mitochondrial Myopathy

NCT ID: NCT05250375

Last Updated: 2025-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-03-24

Study Completion Date

2030-03-24

Brief Summary

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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

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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.

Conditions

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Primary Mitochondrial Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Primary Mitochondrial Myopathy

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.

No interventions assigned to this group

Healthy Controls

Males or females age 0-100 years of age with no history of mitochondrial myopathy symptoms.

No interventions assigned to this group

Eligibility Criteria

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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)


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)

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.


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.
Minimum Eligible Age

0 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Pennsylvania

OTHER

Sponsor Role collaborator

United Mitochondrial Disease Foundation (UMDF)

UNKNOWN

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Zarazuela Zolkipli-Cunningham, MBChB

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Katelynn Stanley, BS

Role: CONTACT

267 426 4961

Jean Flickinger, PT

Role: CONTACT

267 426 4961

Facility Contacts

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Amanda Wellik

Role: primary

267-426-4961

References

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McKay MJ, Baldwin JN, 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):50-6. doi: 10.1016/j.physio.2014.12.002. Epub 2015 Jan 22.

Reference Type BACKGROUND
PMID: 25733400 (View on PubMed)

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.

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PMID: 32926876 (View on PubMed)

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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
PMID: 16801664 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17123819 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22094475 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25652200 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29903433 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31917109 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32518176 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29865090 (View on PubMed)

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.

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

Reference Type BACKGROUND

Other Identifiers

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1R01AR083552-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

16-013364

Identifier Type: -

Identifier Source: org_study_id

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