Myotonic Dystrophy Type 1 (DM1) Deep Phenotyping to Improve Delivery of Personalized Medicine and Assist in the Planning, Design and Recruitment of Clinical Trials
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 213
- 试验地点
- 2
- 主要终点
- Strength and function
研究概览
简要总结
PhenoDM1 will use patient reported outcomes to assess levels of pain, fatigue and quality of life in this cohort. Clinical and functional outcomes will look at muscle wasting and levels of myotonia. DNA, RNA, serum and CSF samples will be taken from all patients so that additional genetic and molecular biomarker analysis can be carried out. A subset of patients will undergo detailed sleep studies along with skeletal muscle MRI of the lower limbs. This study will complement the work of other groups currently looking at myotonic dystrophy type 1 using the same outcomes and measures where possible.
详细描述
Myotonic Dystrophy type I (DM1) is the most common form of adult muscular dystrophy, affecting 1 in 8000 individuals. It is an autosomal dominant disorder with multisystemic involvement of multiple organs and tissues, namely brain, heart, endocrine system, eyes and both smooth and skeletal muscles. It results from the CTG expansion of an untranslated region 3' terminal of the DMPK gene which causes a disturbance of the RNA metabolism, in particular defective splicing of various pre-mRNAs such as the muscular chloride channel (causing myotonia), the insulin receptor (causing diabetes) and others. We will carry out an in-depth characterisation of 400 adult DM1 patients identified from local clinical populations across England and through the national DM Registry. Over a two year period we will take measurements 12 months apart to address specific symptoms that cause major quality of life impairment including muscle weakness, myotonia, excessive daytime sleepiness and cognitive impairment. DNA samples will be collected in order to determine the CTG repeat length and serum samples for biomarker identification. We will carry out muscle MRI and sleep studies in a subset of 50 patients. The implemented measures will capitalise on the efforts of previous cohort studies ensuring that all measures are comparable with existing datasets.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria
- •18 years of age or over
- •Genetic confirmation of Myotonic Dystrophy Type 1
- •Able to consent and willing to participate throughout the duration of the study.
- •Additional Inclusion Criteria for MRI study:
- •Aged between 18 and 55 years
- •Ambulant or ambulant-assisted
- •Additional Inclusion Criteria for sleep study:
- •Aged between 18 and 55 years
排除标准
- •Main Exclusion Criteria
- •Inability to give informed consent
- •If the clinician presumes that the patient will not be able to perform any of the motor function tests involved (Six Minute Walk Test, 30 Seconds Sit and Stand Test, Timed 10-Meter Walk Test)
- •Inability to perform the cardiac and pulmonary assessments
- •Additional Exclusion Criteria for MRI study:
- •Pacemaker, ICD or non-MRI-compatible prosthetic material.
- •Additional Exclusion Criteria for sleep study:
- •ventilated patients
- •patients medicated with stimulants, including Modafinil
- •patients medicated with benzodiazepines or antidepressants
结局指标
主要结局
Strength and function
时间窗: 9-12 months
These assessments include: * Manual Muscle Testing * Quantitative Muscle Testing (Hand Held Myometry, Hand-Grip Dynamometry) * Pulmonary function testing (FVC and MIP) * Functional evaluations (Nine Hole Peg Test, Six Minute Walk Test, 30 Seconds Sit and Stand Test, Timed 10-Meter Walk Test, Scale for Assessment and Rating of Ataxia Scale, Accelerometry Assessment)
次要结局
- Fatigue and Daytime Sleepiness assessment using patient-reported outcomes(9-12 months)
- Cognitive assessment(9-12 months)
- Quality of Life using patient-reported outcomes(9-12 months)
- Pain assessment using patient-reported outcomes(9-12 months)
- Blood and Urine collection for genetic and molecular biomarker analysis(9-12 months)
- Blood collection for Glycated Haemoglobin (HbA1c), Thyroid hormones, Androgens (in males only) analysis(9-12 months)