PhenoDM1 (Myotonic Dystrophy Type 1 Natural History Study)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Myotonic Dystrophy type 1 (DM1) patients Natural History Study |
Outcome Measures
Primary Outcome Measures
- Strength and function [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)
Secondary Outcome Measures
- Cognitive assessment [9-12 months]
These questionnaires include: Mini-Mental State Examination (MMS) Trail Making Test (TMT) Apathy Evaluation Scale (AES)
- Quality of Life using patient-reported outcomes [9-12 months]
These questionnaires include: Individualised Neuromuscular Quality Of Life (InQoL) Myotonic Dystrophy Health Index (MDHI)
- Fatigue and Daytime Sleepiness assessment using patient-reported outcomes [9-12 months]
These questionnaires include: Checklist Individual Strength Epworth Sleepiness Scale Fatigue and Daytime Sleepiness Scale
- Pain assessment using patient-reported outcomes [9-12 months]
These questionnaires include: McGill questionnaire IVR Scale
- Blood and Urine collection for genetic and molecular biomarker analysis [9-12 months]
Collection of: RNA, DNA, Serum and Urine
- Blood collection for Glycated Haemoglobin (HbA1c), Thyroid hormones, Androgens (in males only) analysis [9-12 months]
Other Outcome Measures
- Sleep Study [9-12 months]
Assessment by polysomnography and maintenance of wakefulness test (MWT)
- Skeletal Muscle MRI of the lower extremities [9-12 months]
Three imaging scans will be acquired of the lower extremities: T1-weighted images, TIRM images and Dixon images.
Eligibility Criteria
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:
- 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:
- 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Newcastle-upon-Tyne Hospitals NHS Trust | Newcastle Upon Tyne | Tyne And Wear | United Kingdom | NE1 4LP |
| 2 | University College London Hospitals NHS Foundation Trust, National Hospital for Neurology and Neurosurgery | London | United Kingdom | WC1N 3BG |
Sponsors and Collaborators
- Newcastle-upon-Tyne Hospitals NHS Trust
Investigators
- Principal Investigator: Hanns Lochmuller, MD, FAAN, University of Newcastle Upon-Tyne
- Principal Investigator: Chris Turner, FRCP, PhD, National Hospital for Neurology and Neurosurgery
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 7491