Myotonic Dystrophy 1
Conditions
Keywords
Observational, DMPK, clinical outcomes, multi-system involvement
Brief summary
Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disorder caused by an expanded CTG trinucleotide repeat in the 3' untranslated region of the DMPK gene. Beyond myotonia and progressive skeletal muscle weakness, DM1 involves the cardiac, respiratory, central nervous, gastrointestinal, endocrine, and ocular systems, and respiratory and cardiac involvement are the leading causes of disability and death. Systematic, long-term outcome data in Chinese DM1 patients are lacking. C-DMCOS-DM1 is a multicenter, prospective, observational cohort study that systematically records demographic data, multisystem involvement, and predefined disability-related clinical outcome events in genetically confirmed Chinese DM1 patients, with regular follow-up every 3 to 6 months. The study also collects residual blood, skeletal muscle, myocardium (when a pacemaker is implanted), and urine specimens for transcriptomic and other molecular studies. The aims are to characterize the disease burden of Chinese DM1 patients, identify risk and prognostic factors for disabling outcomes, and build risk-prediction models to inform follow-up, management, and future clinical trials.
Detailed description
This multicenter, prospective, observational cohort study (no randomization, no control, no intervention) enrolls genetically confirmed DM1 patients across Chinese neuromuscular centers and follows them every 3 to 6 months. At baseline and each visit, the study collects demographics, clinical subtype, symptoms and rating scales, manual muscle testing and the Muscular Impairment Rating Scale (MIRS), quantitative motor measures (grip strength, 10-Metre Walk Test \[10MWT\], Video Hand Opening Time \[vHOT\]), cardiac assessment (electrocardiography and 24-hour Holter), pulmonary function testing, echocardiography, laboratory tests, computerized cognitive assessment, and video and voice recordings of gait, hand grip, and facial movement for artificial-intelligence analysis. Wearable devices are encouraged for continuous monitoring of heart rate and heart rate variability, blood oxygen saturation, respiratory rate, sleep and nocturnal respiratory events, and daily physical activity. Predefined disability-related outcome events are tracked cumulatively, including loss of independent ambulation, respiratory failure, non-invasive or invasive mechanical ventilation, tracheostomy, cardiac pacemaker or implantable cardioverter-defibrillator (ICD) implantation, early cataract surgery, malignancy, and death. Residual blood, skeletal muscle, myocardium (when a pacemaker is implanted), and urine specimens are collected for RNA sequencing, mitochondrial DNA analysis, and other molecular studies. Statistical analysis includes descriptive characterization, Kaplan-Meier and Cox proportional-hazards survival analysis, competing-risk models, and multivariable regression to identify risk and prognostic factors and to build risk-prediction models.
Interventions
DIAGNOSTIC_TESTMRI scan
Brain MRI scan to evaluate the integrity of the nervous system; lower limb muscle MRI scan to evaluate fat infiltration in skeletal muscles of the lower limb
DIAGNOSTIC_TESTElectrocardiography
Standard 12-lead electrocardiography or Holter monitoring performed to assess cardiac conduction abnormalities and arrhythmias in patients with DM1.
DIAGNOSTIC_TESTPulmonary function test
Comprehensive pulmonary function testing including spirometry to assess respiratory muscle weakness and restrictive lung disease in DM1 patients.
DIAGNOSTIC_TESTElectrocardiography and 24-hour Holter monitoring
Electrocardiography and 24-hour Holter monitoring
PROCEDURESkeletal muscle biopsy (residual specimen)
Skeletal muscle biopsy (residual specimen)
DEVICEWearable-device continuous physiological monitoring
Wearable-device continuous physiological monitoring (heart rate, blood oxygen saturation, respiration, physical activity, sleep)
BEHAVIORALVideo and voice recording for AI analysis
Video and voice recording for AI analysis (gait, hand grip, facial movement, speech)
Sponsors
Huashan Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
1. Genetically confirmed DM1 (CTG repeat expansion in the 3' untranslated region of the DMPK gene). 2. Any sex. 3. Able to attend regular follow-up and willing to provide and store residual blood, urine, and other biospecimens for research. 4. Voluntary participation with signed informed consent (signed by legal guardian for minors). 5. Consent to use of routine clinical, examination, and follow-up data for research.
Exclusion criteria
1. Unable to comply with study procedures. 2. Unable to provide informed consent, or guardian declines participation. 3. Pregnancy (for MRI safety). 4. Severe, unstable medical condition that precludes assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence and time to first major disability-related clinical outcome event | From enrollment up to 10 years | Proportion of participants experiencing, and time to first occurrence of, predefined disability-related outcome events: loss of independent ambulation, respiratory failure, non-invasive mechanical ventilation, invasive mechanical ventilation, tracheostomy, cardiac pacemaker implantation, implantable cardioverter-defibrillator (ICD) implantation, early cataract surgery, malignancy, and death. Each event is recorded with its date of first occurrence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 10-Metre Walk Test (10MWT) | Baseline, Year 1, Year 3, Year 5, Year 10 | Time in seconds to walk 10 metres, assessing functional mobility. |
| Change in Video Hand Opening Time (vHOT) | Baseline, Year 1, Year 3, Year 5, Year 10 | Time to fully open the hand after making a fist, an objective measure of myotonia severity. |
| Change in Muscular Impairment Rating Scale (MIRS) | Baseline, Year 1, Year 3, Year 5, Year 10 | Five-point clinical rating of muscle impairment in DM1. |
| Change in forced vital capacity (FVC, % predicted) | Baseline, Year 1, Year 3, Year 5, Year 10 | Pulmonary function measure reflecting respiratory involvement. |
| Change in Epworth Sleepiness Scale (ESS) | Baseline, Year 1, Year 3, Year 5, Year 10 | 0 to 24 scale of daytime sleepiness; higher scores indicate greater sleepiness. |
| Change in Fatigue Severity Scale (FSS) | Baseline, Year 1, Year 3, Year 5, Year 10 | 9-item fatigue scale; higher scores indicate more severe fatigue. |
Countries
China
Contacts
STUDY_DIRECTORChongbo Zhao, PhD
Huashan Hospital
Outcome results
None listed