Chinese Multicenter Clinical Outcome Cohort Study of Myotonic Dystrophy Type 1 (C-DMCOS-DM1)

Официальное название

A Multicenter, Prospective, Observational Cohort Study of Multi-System Involvement and Disability-Related Clinical Outcomes in Chinese Patients With Myotonic Dystrophy Type 1 (C-DMCOS-DM1)

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест MRI 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
• Диагностический тест Electrocardiography
  Standard 12-lead electrocardiography or Holter monitoring performed to assess cardiac conduction abnormalities and arrhythmias in patients with DM1.
• Диагностический тест Pulmonary function test
  Comprehensive pulmonary function testing including spirometry to assess respiratory muscle weakness and restrictive lung disease in DM1 patients.
• Диагностический тест Electrocardiography and 24-hour Holter monitoring
  Electrocardiography and 24-hour Holter monitoring
• Процедура Skeletal muscle biopsy (residual specimen)
  Skeletal muscle biopsy (residual specimen)
• Устройство Wearable-device continuous physiological monitoring
  Wearable-device continuous physiological monitoring (heart rate, blood oxygen saturation, respiration, physical activity, sleep)
• Поведенческое Video and voice recording for AI analysis
  Video and voice recording for AI analysis (gait, hand grip, facial movement, speech)

Первичные конечные точки

• Cumulative incidence and time to first major disability-related clinical outcome event [Срок оценки: From enrollment up to 10 years]

Вторичные конечные точки (6)

• Change in 10-Metre Walk Test (10MWT) [Срок оценки: Baseline, Year 1, Year 3, Year 5, Year 10]
• Change in Video Hand Opening Time (vHOT) [Срок оценки: Baseline, Year 1, Year 3, Year 5, Year 10]
• Change in Muscular Impairment Rating Scale (MIRS) [Срок оценки: Baseline, Year 1, Year 3, Year 5, Year 10]
• Change in forced vital capacity (FVC, % predicted) [Срок оценки: Baseline, Year 1, Year 3, Year 5, Year 10]
• Change in Epworth Sleepiness Scale (ESS) [Срок оценки: Baseline, Year 1, Year 3, Year 5, Year 10]
• Change in Fatigue Severity Scale (FSS) [Срок оценки: Baseline, Year 1, Year 3, Year 5, Year 10]

Критерии участия

Критерии включения

• Genetically confirmed DM1 (CTG repeat expansion in the 3' untranslated region of the DMPK gene).
• Any sex.
• Able to attend regular follow-up and willing to provide and store residual blood, urine, and other biospecimens for research.
• Voluntary participation with signed informed consent (signed by legal guardian for minors).
• Consent to use of routine clinical, examination, and follow-up data for research.

Критерии исключения

• Unable to comply with study procedures.
• Unable to provide informed consent, or guardian declines participation.
• Pregnancy (for MRI safety).
• Severe, unstable medical condition that precludes assessments.

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

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 22 центра

• Chinese People's Liberation Army General Hospital — Пекин
• Peking University First Hospital — Пекин
• First Affiliated Hospital of Chongqing Medical University — Чунцин
• Fujian Medical University Union Hospital — Фучжоу
• Southern Hospital of Southern Medical University — Гуанчжоу
• The Third Hospital of Hebei Medical University — Shijiazhuang
• Wuhan University People's Hospital — Ухань
• Zhongda Hospital Southeast University — Нанкин
• … и ещё 14 центров

Публикации

• Zhong H, Zeng L, Yu X, Ke Q, Dong J, Chen Y, Luo L, Chang X, Guo J, Wang Y, Xiong H, Liu R, Liu C, Wu J, Lin J, Xi J, Zhu W, Tan S, Liu F, Lu J, Zhao C, Luo S. Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1. Orphanet J Rare Dis. 2024 Mar 7;19(1):103. doi: 10.1186/s13023-024-03114-z. PMID 38454488

Идентификаторы

NCT: NCT06101940 · KY2020-008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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