PhenoDM1 (Myotonic Dystrophy Type 1 Natural History Study)

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Myotonic Dystrophy Type 1 (DM1) Deep Phenotyping to Improve Delivery of Personalized Medicine and Assist in the Planning, Design and Recruitment of Clinical Trials

Conditions
-----------------
Myotonic Dystrophy Type 1

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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: 1. Aged between 18 and 55 years Exclusion Criteria: 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: 1. 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Myotonic Dystrophy type 1 (DM1) patients<br>Natural History Study | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Strength and function | 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) | 9-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive assessment | These questionnaires include: Mini-Mental State Examination (MMS) Trail Making Test (TMT) Apathy Evaluation Scale (AES) | 9-12 months | 
| Quality of Life using patient-reported outcomes | These questionnaires include: Individualised Neuromuscular Quality Of Life (InQoL) Myotonic Dystrophy Health Index (MDHI) | 9-12 months | 
| Fatigue and Daytime Sleepiness assessment using patient-reported outcomes | These questionnaires include: Checklist Individual Strength Epworth Sleepiness Scale Fatigue and Daytime Sleepiness Scale | 9-12 months | 
| Pain assessment using patient-reported outcomes | These questionnaires include: McGill questionnaire IVR Scale | 9-12 months | 
| Blood and Urine collection for genetic and molecular biomarker analysis | Collection of: RNA, DNA, Serum and Urine | 9-12 months | 
| Blood collection for Glycated Haemoglobin (HbA1c), Thyroid hormones, Androgens (in males only) analysis |  | 9-12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Myotonic Dystrophy type 1, DM1, Muscular Dystrophy, Neuromuscular Diseases