AzTrials
AzTrials

Congenital MyopathiesNCT07914049

Personalized Disease Modeling for Rare Genetic Myopathies

An observational study of Congenital Myopathies and Muscular Dystrophy, run by Akron Children's Hospital at 1 site in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial summary

The goal of this observational study is to learn how rare genetic muscle diseases change over time and whether muscle cells grown from a participant's blood can help researchers understand the disease. Read more about this study

Who is it for?
Ages Up to 21 years
Conditions the study is for
Congenital Myopathies, Muscular Dystrophy
How many people
3 participants
Where
1 siteUnited States
Study dates
22 Sep 2026to Dec 2028
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 Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Study population: Patients with genetic myopathies and ultra-rare mutations potentially amenable to personalized antisense oligonucleotide therapy

Who may be able to join

  • • Patient age at time of consent is <21 years.
  • Clinically confirmed genetic muscle disease* with either:
  • a pathogenic or likely pathogenic variant in a disease-causing gene11, or
  • a variant of uncertain significance that is considered by the investigators to be potentially causative of the patient's neuromuscular phenotype**.
  • The identified variant is theoretically amenable to at least one of the following RNA-targeted therapeutic strategies12 described below and based on published guidelines ***:
  • ASO-mediated splice modulation through forced exon inclusion or pseudoexon exclusion
Show all 22Show fewer
  • ASO-mediated allele-specific knockdown
  • Variant population frequency ≤1:100,000 based on reference databases (e.g., gnomAD).
  • The clinical phenotype is sufficiently severe and/or progressive to warrant consideration of future investigational therapeutic approaches, as determined by consensus of the trial team, taking into account factors such as:
  • Ambulatory status
  • Respiratory involvement
  • Dysphagia
  • Functional independence
  • Expected disease progression
  • Frequency of hospitalization and/or ICU admission
  • Disease course is not expected to progress to death or end-stage pathology within a timeframe that would preclude meaningful longitudinal observation or potential future interventional study planning (anticipated ≥4 years).
  • For patients with Duchenne muscular dystrophy, glucocorticoid dosing (adjusted for weight) is stable for the preceding 3 months prior to start date.
  • Willingness to participate in all study-related observational assessments and to adhere to standard-of-care clinical management.
  • Parent or caregiver is fluent in English to ensure valid administration of standardized outcome measures and informed consent procedures.
  • Genetic muscle disease is defined as a genetically determined condition in which the primary phenotype arises from skeletal muscle pathology. Disorders may have extra-muscular manifestations (e.g., neurocognitive features in Duchenne muscular dystrophy), but skeletal muscle dysfunction must be the primary driver of impairment. Eligible diagnoses include congenital muscular dystrophies, congenital myopathies, dystrophinopathies, limb-girdle muscular dystrophies, and skeletal muscle channelopathies. Confirmation of the variant of interest must be obtained through DNA sequencing performed in a CLIA-certified laboratory.
  • For subjects with variants of uncertain significance by standard American College of Medical Genetics (ACMG) criteria, orthogonal pathogenicity data will be required. This is expected in cases of deep intronic variants, where clinical genetic reports may not account for RNA sequencing data obtained from external labs.
  • ASO-amenable variants will be defined based on the variant type and mechanism of disease. For subjects with deep intronic pathogenic variants, evidence of a pseudoexon or abnormal exclusion of an exon by RNA sequencing data will be required for study participation. For subjects with dominant, gain of function variants, evidence from literature for toxic gain of function as a mechanism of disease will be required and evidence from literature that haploinsufficiency is not a disease mechanism will also be required.

Who cannot join

  • • Availability of an effective (expected to halt all disease progression) disease-modifying therapy for the patient's condition at the time of enrollment.
  • Pathogenic or suspected causative variant with population frequency >1:100,000 based on standard reference databases.
  • Variants with mechanisms not compatible with the therapeutic strategies under evaluation, including:
  • Splice-site variants within 10 bp of canonical donor or acceptor sites
  • Dominant variants acting through haploinsufficiency
  • Recessively acting missense variants
Show all 16Show fewer
  • Whole-gene deletions
  • Mitochondrially encoded variants
  • Current enrollment in, or planned enrollment in, another interventional clinical trial.
  • Pregnancy or intention to become pregnant during the anticipated study period.
  • Inability of the subject or family to comply with study procedures.
  • Chronic thrombocytopenia (platelet count <75,000/uL that is not transient) or coagulation disorders (International normalized ratio (INR)>1.3, activated partial thromboplastin time >40 seconds, or symptomatic von Willebrand disease)
  • Comorbid conditions that would interfere with the performance or interpretation of key outcome measures, including but not limited to:
  • Severe intellectual disability
  • Severe systemic non-neuromuscular disease (e.g., advanced liver disease) or central nervous system injury (e.g., anoxic brain injury)
  • Active malignancy undergoing treatment

Trial locations and contacts

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

United States1 site

  • Akron Children's Hospital

    Akron, Ohio, 44308

Other trials in United States

About this study

The goal of this observational study is to learn how rare genetic muscle diseases change over time and whether muscle cells grown from a participant's blood can help researchers understand the disease. The study will include children and young adults under age 21 with a genetic muscle disease and a rare genetic change that may be suitable for a future personalized treatment.

The main questions are:

Read more

How do each participant's muscle strength, movement, and health change over time? Can muscle cells grown from a participant's blood show how their genetic change affects muscle? For some participants, can a potential treatment improve those cells in the laboratory?

Participants will be followed for approximately 2 years. Researchers will review their health, measure muscle function, and ask participants and caregivers about quality of life. Assessments may also include blood tests, muscle ultrasound, muscle MRI without sedation, optional nerve and muscle electrical measurements, and ankle-worn movement sensors for participants who walk.

Researchers will use a blood sample to grow muscle cells in the laboratory to better understand how a muscle condition develops and what potential treatments might work.

Read the detailed description

The goal of this observational study is to learn how rare genetic muscle diseases change over time and whether muscle cells grown from a participant's blood can help researchers understand the disease. The study will include children and young adults under age 21 with a genetic muscle disease and a rare genetic change that may be suitable for a future personalized treatment.

The main questions are:

How do each participant's muscle strength, movement, and health change over time? Can muscle cells grown from a participant's blood show how their genetic change affects muscle? For some participants, can a potential treatment improve those cells in the laboratory?

Participants will be followed for at least 2 years and up to 4 years. They will have full clinic visits about every 6 months and shorter assessments about every 3 months. Researchers will review their health, measure muscle function, and ask participants and caregivers about quality of life. Assessments may also include blood tests, muscle ultrasound, muscle MRI without sedation, optional nerve and muscle electrical measurements, and ankle-worn movement sensors for participants who walk.

Researchers will use a blood sample to grow muscle cells in the laboratory. For some participants, they will test experimental antisense oligonucleotides, which are molecules designed to change how a gene's instructions are used, in those cells only. No participant will receive an experimental treatment in this study. A future treatment study would require separate enrollment and consent.

Keywords
antisense oligonucleotide, myopathy, congenital myopathy, personalized therapy, n-of-1, ultra-rare, nano-rare, muscular dystrophy, disease modeling, natural history
Medical subject headings
Myotonia Congenita, Muscular Dystrophies, Muscular Diseases

What participants receive

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

Study groups in NCT07914049
Study groupRoleWhat they receive
Rare MyopathyParticipants with rare genetic myopathies potentially amenable to personalized antisense oligonucleotide therapy

What is being measured

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

  1. Medical Research Council (MRC) sum score

    Sum of bilateral Medical Research Council grades for arm abduction, arm flexion, arm extension, hip flexion, knee extension, and ankle dorsiflexion. Scoring values are 0 (Minimum) to 60 (Maximum), with a higher score representing better outcomes.

    Measured: Enrollment to 2 years

  2. North Star Ambulatory Assessment (NSAA)

    The North Star Ambulatory Assessment (NSAA) is a 17-item rating scale that is used to measure functional motor abilities in ambulant children with Duchenne Muscular Dystrophy (DMD). It is usually used to monitor the progression of the disease and treatment effects. The activities in the 17-itm scale are graded as follows:

    2 - "Normal" - no obvious modification of activity

    1 - Modified method but achieves goal independent of physical assistance from another 0 - Unable to achieve independently This scale is ordinal with 34 as the maximum score indicating fully-independent function. The higher the score, the better outcome.

    Measured: From enrollment to 2 years

Secondary outcomes (16)

  1. 10 Meter Walk/Run

    Best time on 10-meter walk or run

    Measured: Enrollment to 2 years

  2. Supine to stand velocity

    Fastest time from lying to standing

    Measured: Enrollment to 2 years

  3. Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0 GCS)

    Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and Duchenne Muscular Dystrophy (DMD) Module : Patient-reported outcome measures (PROM) used to assess health-related quality of life in children with DMD. The PedsQL 4.0 Generic Core contains 23 items assessing physical, emotional, social, and school functioning, while the DMD Module includes disease-specific items addressing daily activities, treatment barriers, worry, and communication. Child self-report and parent proxy versions use a 5-point Likert scale (0 = never a problem to 4 = almost always a problem; ages 5-7 use a simplified 3-point scale). Responses are reverse-scored and transformed to a 0-100 scale, with higher scores indicating better quality of life. Scores are calculated for individual domains and total summary measures.

    Measured: Enrollment to 2 years

  4. Patient Global Impression of Change (PGI-C)

    Patient Global Impression of Change (PGI-C) and Clinician Global Impression of Change (CGI-C): Single-item assessments completed by the patient that measure overall change in the participant's condition since the start of treatment. Scores range from 1 to 7, where 1 = very much improved, 4 = no change, and 7 = very much worse. Lower scores indicate improvement, higher scores indicate worsening, and mid-range scores indicate little or no change.

    Measured: Enrollment to 2 years

  5. Clinician Global Impression of Change (CGI-C)

    Clinician Global Impression of Change (CGI-C): Single-item assessments completed by the clinician (CGI-C) that measure overall change in the participant's condition since the start of treatment. Scores range from 1 to 7, where 1 = very much improved, 4 = no change, and 7 = very much worse. Lower scores indicate improvement, higher scores indicate worsening, and mid-range scores indicate little or no change.

    Measured: Enrollment to 2 years

  6. SV95C

    95%ile stride velocity based on wearable biosensor

    Measured: Enrollment to 2 years

  7. Grip strength

    Dynamometry for grip strength, measured in kilograms taken as the best of 3 trials on the best side

    Measured: Enrollment to 2 years

  8. Muscle Fat fraction

    Muscle Fat Fraction: Quantitative MRI assessment of muscle composition performed using an 8-point Dixon MRI sequence of the right thigh on a 3 Tesla (3T) MRI scanner. Muscle fat fraction is reported as the percentage of fat-containing voxels within the muscle, with higher percentages indicating greater fatty infiltration of muscle tissue.

    Measured: Enrollment to 2 years

  9. Muscle thickness by ultrasound

    Standardized muscle thickness at standard positions on the left side measured by ultrasound and summed (biceps, vastus lateralis, and tibialis anterior)

    Measured: Enrollment to 2 years

  10. Muscle ultrasound grayscale intensity

    Mean ultrasound grayscale intensity at selected muscles measured in pixel brightness within a manual region of interest

    Measured: Enrollment to 2 years

  11. Muscle ultrasound grayscale variability

    Standard deviation of pixel grayscale intensity within a manually selected region of interest at selected muscles.

    Measured: Enrollment to 2 years

  12. FVC

    Forced vital capacity as percent predicted

    Measured: Enrollment to 2 years

  13. 4SC

    Timed 4 stair climb velocity

    Measured: Enrollment to 2 years

  14. Electrophysiology - Compound Motor Action Potential (CMAP)

    Compound Muscle Action Potential (CMAP) at standard sites: A noninvasive electrophysiologic measure of the muscle's electrical response following nerve stimulation. CMAP amplitude and area are used to assess the integrity of motor nerve pathways and overall muscle activation. Reported as amplitude (millivolts [mV]) and, when assessed, area (millivolt-milliseconds [mV·ms]). Higher values generally indicate better neuromuscular function; there is no fixed range for this assessment (no minimum or maximum).

    Measured: Enrollment to 2 years

  15. Electrophysiology - Motor Unit Number Index (MUNIX)

    Motor Unit Number Index (MUNIX) at standard sites: A noninvasive electrophysiologic measure that estimates the number of functioning motor units within a muscle using nerve conduction and surface electromyography data. Calculated from CMAP and surface electromyography (EMG) recordings and reported as a unitless index score. Higher values generally indicate greater preservation of motor units; there is no fixed range for this assessment (no minimum or maximum).

    Measured: Enrollment to 2 years

  16. Electrophysiology - Motor Unit Size Index (MUSIX)

    Motor Unit Size Index (MUSIX): An electrophysiologic measure derived from CMAP and MUNIX results that estimates the average size of functioning motor units. Changes in MUSIX may reflect compensatory enlargement of remaining motor units associated with neuromuscular disease progression. Derived from CMAP and MUNIX measurements and reported as a unitless index score representing estimated average motor unit size. There is no minimum or maximum value.

    Measured: Enrollment to 2 years

Timeline

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

  1. First posted3 Nov 2026
  2. Study start22 Sep 2026
  3. Primary completionDec 2028 (estimated)
  4. Study completionDec 2028 (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
Case only
Time perspective
Prospective
Enrolment
3 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07914049
Sponsor's protocol ID
2026-078
Status last verified
Oct 2026
First submitted
14 Oct 2026
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Individual patient, anonymous biosensor data and basic clinical information will be shared with partner organization as specified by our IRB approved protocol. Additional IPD may be shared on a case-by-case basis with additional consent and IRB approval due to the small sample size, presence of genomic information, and to respect subject confidentiality.

Publications

  • Almarwani M, Perera S, VanSwearingen JM, Sparto PJ, Brach JS. The test-retest reliability and minimal detectable change of spatial and temporal gait variability during usual over-ground walking for younger and older adults. Gait Posture. 2016 Feb;44:94-9. doi: 10.1016/j.gaitpost.2015.11.014. Epub 2015 Nov 30.

    PubMed 27004639

  • Chiba S, Okuno Y. In Silico Prediction and Selection of Exon-Skipping Antisense Oligonucleotide Sequences Using eSkip-Finder. Methods Mol Biol. 2025;2964:109-116. doi: 10.1007/978-1-0716-4730-1_6.

    PubMed 40720013

  • Zhu A, Chiba S, Shimizu Y, Kunitake K, Okuno Y, Aoki Y, Yokota T. Ensemble-Learning and Feature Selection Techniques for Enhanced Antisense Oligonucleotide Efficacy Prediction in Exon Skipping. Pharmaceutics. 2023 Jun 24;15(7):1808. doi: 10.3390/pharmaceutics15071808.

    PubMed 37513994

  • Chiba S, Lim KRQ, Sheri N, Anwar S, Erkut E, Shah MNA, Aslesh T, Woo S, Sheikh O, Maruyama R, Takano H, Kunitake K, Duddy W, Okuno Y, Aoki Y, Yokota T. eSkip-Finder: a machine learning-based web application and database to identify the optimal sequences of antisense oligonucleotides for exon skipping. Nucleic Acids Res. 2021 Jul 2;49(W1):W193-W198. doi: 10.1093/nar/gkab442.

    PubMed 34104972

  • Kang S, Lee D, Hwang G, Lee K, Kang M. ASOptimizer: optimizing chemical diversity of antisense oligonucleotides through deep learning. Nucleic Acids Res. 2025 Jul 7;53(W1):W39-W44. doi: 10.1093/nar/gkaf392.

    PubMed 40377084

  • Kimi J, Korczak P, Vialet B, Roubin E, Barthelemy P, Campagne S, Malard F. ASOG: AntiSense Oligonucleotide Generator. Comput Struct Biotechnol J. 2025 Sep 16;27:4145-4150. doi: 10.1016/j.csbj.2025.09.022. eCollection 2025.

    PubMed 41050468

  • Pinton L, Khedr M, Lionello VM, Sarcar S, Maffioletti SM, Dastidar S, Negroni E, Choi S, Khokhar N, Bigot A, Counsell JR, Bernardo AS, Zammit PS, Tedesco FS. 3D human induced pluripotent stem cell-derived bioengineered skeletal muscles for tissue, disease and therapy modeling. Nat Protoc. 2023 Apr;18(4):1337-1376. doi: 10.1038/s41596-022-00790-8. Epub 2023 Feb 15.

    PubMed 36792780

  • Maffioletti SM, Sarcar S, Henderson ABH, Mannhardt I, Pinton L, Moyle LA, Steele-Stallard H, Cappellari O, Wells KE, Ferrari G, Mitchell JS, Tyzack GE, Kotiadis VN, Khedr M, Ragazzi M, Wang W, Duchen MR, Patani R, Zammit PS, Wells DJ, Eschenhagen T, Tedesco FS. Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering. Cell Rep. 2018 Apr 17;23(3):899-908. doi: 10.1016/j.celrep.2018.03.091.

    PubMed 29669293

  • Chal J, Al Tanoury Z, Hestin M, Gobert B, Aivio S, Hick A, Cherrier T, Nesmith AP, Parker KK, Pourquie O. Generation of human muscle fibers and satellite-like cells from human pluripotent stem cells in vitro. Nat Protoc. 2016 Oct;11(10):1833-50. doi: 10.1038/nprot.2016.110. Epub 2016 Sep 1.

    PubMed 27583644

  • Barnard AM, Willcocks RJ, Finanger EL, Daniels MJ, Triplett WT, Rooney WD, Lott DJ, Forbes SC, Wang DJ, Senesac CR, Harrington AT, Finkel RS, Russman BS, Byrne BJ, Tennekoon GI, Walter GA, Sweeney HL, Vandenborne K. Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy. PLoS One. 2018 Mar 19;13(3):e0194283. doi: 10.1371/journal.pone.0194283. eCollection 2018.

    PubMed 29554116

  • Vandenborne K, Walter GA, Straub V, Willcocks RJ, Forbes SC, Mercuri EM, Muntoni F, Ding K, Ennamuri S, Reid C, Murphy AP, Manfrini M, Mendell JR, Elkins JS, Rodino-Klapac LR. Quantitative Muscle Magnetic Resonance Outcomes in Patients With Duchenne Muscular Dystrophy: An Exploratory Analysis From the EMBARK Randomized Clinical Trial. JAMA Neurol. 2025 Jul 1;82(7):734-744. doi: 10.1001/jamaneurol.2025.0992.

    PubMed 40354061

  • Willcocks RJ, Rooney WD, Triplett WT, Forbes SC, Lott DJ, Senesac CR, Daniels MJ, Wang DJ, Harrington AT, Tennekoon GI, Russman BS, Finanger EL, Byrne BJ, Finkel RS, Walter GA, Sweeney HL, Vandenborne K. Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort. Ann Neurol. 2016 Apr;79(4):535-47. doi: 10.1002/ana.24599. Epub 2016 Feb 19.

    PubMed 26891991

  • Dahlqvist JR, Widholm P, Leinhard OD, Vissing J. MRI in Neuromuscular Diseases: An Emerging Diagnostic Tool and Biomarker for Prognosis and Efficacy. Ann Neurol. 2020 Oct;88(4):669-681. doi: 10.1002/ana.25804. Epub 2020 Jul 1.

    PubMed 32495452

  • Triplett WT, Baligand C, Forbes SC, Willcocks RJ, Lott DJ, DeVos S, Pollaro J, Rooney WD, Sweeney HL, Bonnemann CG, Wang DJ, Vandenborne K, Walter GA. Chemical shift-based MRI to measure fat fractions in dystrophic skeletal muscle. Magn Reson Med. 2014 Jul;72(1):8-19. doi: 10.1002/mrm.24917. Epub 2013 Sep 4.

    PubMed 24006208

  • Ayyar Gupta V, Pitchforth JM, Domingos J, Ridout D, Iodice M, Rye C, Chesshyre M, Wolfe A, Selby V, Mayhew A, Mazzone ES, Ricotti V, Hogrel JY, Niks EH, de Groot I, Servais L, Straub V, Mercuri E, Manzur AY, Muntoni F; iMDEX Consortium and the U.K. NorthStar Clinical Network. Determining minimal clinically important differences in the North Star Ambulatory Assessment (NSAA) for patients with Duchenne muscular dystrophy. PLoS One. 2023 Apr 26;18(4):e0283669. doi: 10.1371/journal.pone.0283669. eCollection 2023.

    PubMed 37099511

Questions about this trial

What is this clinical trial studying?

An observational study of Congenital Myopathies and Muscular Dystrophy, run by Akron Children's Hospital 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?

The sponsor lists 22 inclusion and 16 exclusion criteria. 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: enrolling by invitation, as of the sponsor's last update on 3 Nov 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Medical Research Council (MRC) sum score (time frame: Enrollment to 2 years). The study lists 2 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 NCT07914049, which also lists 31 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 3 Nov 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