Natural History Study of Mitochondrial Myopathy

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Muscle Strength of MM-COAST [Срок оценки: through study completion, an average of 5 years]
• Balance of the MM-COAST [Срок оценки: through study completion, an average of 5 years]
• Dexterity of the MM-COAST [Срок оценки: through study completion, an average of 5 years]
• Mitochondrial Disease Burden for Adults [Срок оценки: through study completion, an average of 5 years]
• Mitochondrial Disease Burden for Children [Срок оценки: through study completion, an average of 5 years]
• Challenges in Activities of Daily Life (ADLs) [Срок оценки: through study completion, an average of 5 years]
• Functional Tasks of the Mitochondrial Myopathy Functional Scale (MMFS) [Срок оценки: through study completion, an average of 5 years]
• Clinical Progression: Survival [Срок оценки: through study completion, an average of 5 years]
• Clinical Progression: Growth [Срок оценки: through study completion, an average of 5 years]
• Clinical Progression: Other Illnesses [Срок оценки: through study completion, an average of 5 years]

Вторичные конечные точки (4)

• Cerebellar Ataxia Outcome Measure for Primary Mitochondrial Disease (PMD) [Срок оценки: through study completion, an average of 5 years]
• Clinical Meaningfulness of Ataxia Quantification. [Срок оценки: through study completion, an average of 5 years]
• Evaluation of Health-Related Quality of Life by PedsQL [Срок оценки: through study completion, an average of 5 years]
• Evaluation of daily functional activities by PEDI-CAT [Срок оценки: through study completion, an average of 5 years]

Критерии участия

MM Cohort Inclusion Criteria

• Males or females age 0-100 years of age
• 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.
• Exhibits myopathy (exercise intolerance, muscle strength, fatigue) relating to Mitochondrial disease in the opinion of the investigator
• 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

• Male or female fetuses
• Non English speakers
• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
• 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

• Males or females age 0-100 years of age
• No history of mitochondrial myopathy symptoms
• Able to provide written consent or parental permission and child assent., approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)
• 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

• Male or female fetuses
• Non English speakers
• Mitochondrial disorder established by confirmed genetic or biochemical mutation in mtDNA or nuclear DNA
• Exhibits myopathy (exercise intolerance, muscle strength, fatigue) relating to Mitochondrial disease
• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
• Individual is listed as a study staff member in eIRB, OR individual is a family member of a study staff member listed in eIRB
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Children's Hospital of Philadelphia — Philadelphia

Публикации

• 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):5 PMID 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. PMID 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 Insi PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 29903433

Идентификаторы

NCT: NCT05250375 · 16-013364 · 1R01AR083552-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗