Longitudinal Evaluation of Neuromuscular Involvement in Type 1 Myotonic Dystrophy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Determine sensitivity to changes in neuromuscular functional criteria
研究概览
简要总结
Primary objective: To determine the sensitivity to change of neuromuscular functional outcomes during the natural (non-interventional) progression of myotonic dystrophy type 1 (DM1), in order to identify the most relevant and robust outcome measures for use in therapeutic trials.
Secondary objective: To compare patients with DM1 to healthy control subjects to assess the discriminative power of biomechanical and electrophysiological parameters.
Study design: This is an open-label, single-center observational study with no direct individual benefit.
Participants: Thirty patients with DM1 will be evaluated three times over a three-year period, while thirty control subjects will be assessed once.
Timeline: The planned inclusion period is 12 months, with a follow-up duration of 36 months, resulting in a total study duration of 48 months.
Functional assessment-particularly muscle strength-is essential for both diagnosis and longitudinal monitoring of neuromuscular diseases. In therapeutic trials, outcome measures must meet strict scientific requirements, including precision, sensitivity, and reliability. Muscle strength is frequently used as a primary or secondary endpoint in trials targeting neuromuscular disorders. Even modest functional improvements resulting from therapy must be detectable with sensitive measurement tools.
Myotonic dystrophy is the most common muscular dystrophy in adults, with an estimated prevalence of 1 in 8,000. It is a genetic disorder inherited in an autosomal dominant manner. Two genetically distinct forms are recognized: myotonic dystrophy type 1 (DM1, or Steinert disease) and the rarer, more recently identified type 2 (DM2). This study focuses on DM1 due to its higher prevalence and greater clinical severity.
The study will assess parameters related to myotonia, muscle strength, motor function, and neuromuscular excitability. Patients will be evaluated every 18 months over a three-year period. Control subjects will undergo a single assessment. The expected outcome is the identification of the most robust and sensitive parameters for longitudinal monitoring of DM1 patients, particularly in the context of future therapeutic trials.
A similar study will be conducted in parallel in Quebec (Principal Investigator: Prof. Jack Pumirat, CHU de Québec). Data common to both centers will be analyzed jointly.
详细描述
Background and Rationale Assessment of functional capacities-particularly muscle strength-is essential for both diagnosis and follow-up of patients with neuromuscular diseases. In therapeutic trials, measurement tools must meet strict scientific requirements: accuracy, sensitivity, and reliability. Muscle strength is frequently used as a primary or secondary outcome in clinical trials. Even small functional improvements must be detectable to demonstrate therapeutic benefit.
Myotonic dystrophy is the most common adult muscular dystrophy (prevalence ~1/8,000). It is an autosomal dominant genetic disorder with two distinct forms: type 1 (DM1, Steinert disease) and type 2 (DM2), the latter being rarer. This study focuses on DM1 because of its higher prevalence and more severe clinical manifestations.
More than a century after its first description, DM1 remains highly complex. It shows extreme clinical variability in:
- Age of onset (from congenital or prenatal forms to late-onset after age 60),
- Severity (from asymptomatic to severe neonatal forms),
- Initial organ involvement (heart, central nervous system, skeletal muscle, eye, etc.).
Marked intrafamilial variability is also observed.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For patients:
- •Diagnosed with myotonic dystrophy type 1 confirmed by genetic analysis
- •Presenting with motor weakness (MIRS score of 3 or 4)
- •Able to walk for ten minutes
- •Able to be informed and provide informed consent
- •Affiliated with a French social security scheme
- •For healthy subjects:
- •Matched in age (± 1 year) and sex to patients
- •Able to be informed and provide informed consent
- •Affiliated with a French social security scheme
排除标准
- •for patients and control subjects
- •Participation in another ongoing biomedical research study
- •Orthopaedic disorders of the ankle or hand
- •Progressive cancer
- •Insulin-dependent diabetes
- •Uncontrolled heart disease, congestive heart failure, uncontrolled heart rhythm disorders (supraventricular or ventricular) or severe cardiac conduction disorders (AVB II or III or HV > 70 ms) without pacemaker (patients with pacemakers may be included) [echocardiography within one year prior to inclusion]
- •Unstabilised and uncontrolled hypertension under treatment (or treated with Propranolol, Prazosin or Clonidine) or blood pressure greater than 160/90 mmHg in the supine position
- •Dementia syndrome, major depressive disorder
- •History of drug or alcohol abuse in the last six months
- •Vital capacity < 50% or total lung capacity < 50%, daytime mechanical ventilation (EFR less than 2 years old)
- •Hypercapnia (PaCO2 ≥ 8 Kpa or 60 mmHg) (blood gas less than 2 years old)
- •Visual disorders incompatible with the performance of the tests (e.g. cataracts, etc.)
- •Women who are pregnant, breastfeeding or not using effective contraception
- •Patients treated with cyclosporine
- •Any condition that, in the investigator's opinion, would be incompatible with the proper conduct of the study.
研究组 & 干预措施
DM1 patients
Adults, no intervention
干预措施: 9-hole test (Other)
DM1 patients
Adults, no intervention
干预措施: Balance measurement (Other)
Healthy controls
Adults, no intervention
干预措施: Quantification of myotonia (Other)
Healthy controls
Adults, no intervention
干预措施: MyoAnkle (Other)
Healthy controls
Adults, no intervention
干预措施: Measurement of exercise-induced fatigue (Other)
Healthy controls
Adults, no intervention
干预措施: Moviplate (Other)
DM1 patients
Adults, no intervention
干预措施: Test du Box and Blocks (Other)
DM1 patients
Adults, no intervention
干预措施: Purdue board test (Other)
DM1 patients
Adults, no intervention
干预措施: Quantification of myotonia (Other)
DM1 patients
Adults, no intervention
干预措施: MyoAnkle (Other)
DM1 patients
Adults, no intervention
干预措施: Measurement of exercise-induced fatigue (Other)
DM1 patients
Adults, no intervention
干预措施: Moviplate (Other)
DM1 patients
Adults, no intervention
干预措施: 6-minute walk test (Other)
Healthy controls
Adults, no intervention
干预措施: 6-minute walk test (Other)
Healthy controls
Adults, no intervention
干预措施: Test du Box and Blocks (Other)
Healthy controls
Adults, no intervention
干预措施: Purdue board test (Other)
Healthy controls
Adults, no intervention
干预措施: 9-hole test (Other)
Healthy controls
Adults, no intervention
干预措施: Balance measurement (Other)
结局指标
主要结局
Determine sensitivity to changes in neuromuscular functional criteria
时间窗: 18 and 36 months after baseline
Determine sensitivity to changes in neuromuscular functional criteria during the natural progression (non-interventional follow-up) of patients with myotonic dystrophy type 1 in order to select the most relevant follow-up criteria during a therapeutic trial.
次要结局
- Comparison of variables from patients with myotonic dystrophy type 1 and control subjects(Baseline)