PhenoDM1 (Myotonic Dystrophy Type 1 Natural History Study)

Myotonic Dystrophy Type 1 Clinical Trial

— PhenoDM1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02831504
• Other study ID #: 7491
• Status: Completed
• Start date: August 2015
• Est. completion date: October 31, 2018

Study information

• Verified date: April 2021
• Source: Newcastle-upon-Tyne Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: October 31, 2018
• Est. primary completion date: October 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Main Inclusion Criteria

1. 18 years of age or over

2. Genetic confirmation of Myotonic Dystrophy Type 1

3. Able to consent and willing to participate throughout the duration of the study.

Additional Inclusion Criteria for MRI study:

1. Aged between 18 and 55 years

2. Ambulant or ambulant-assisted

Additional Inclusion Criteria for sleep study:

1. Aged between 18 and 55 years

Exclusion Criteria:

Main Exclusion Criteria

1. Inability to give informed consent

2. 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)

3. 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:

1. ventilated patients

2. patients medicated with stimulants, including Modafinil

3. patients medicated with benzodiazepines or antidepressants

Related Conditions & MeSH terms

• Myotonic Dystrophy
• Myotonic Dystrophy Type 1

Locations

Country	Name	City	State
United Kingdom	University College London Hospitals NHS Foundation Trust, National Hospital for Neurology and Neurosurgery	London
United Kingdom	Newcastle-upon-Tyne Hospitals NHS Trust	Newcastle Upon Tyne	Tyne And Wear

Sponsors (1)

Lead Sponsor	Collaborator
Newcastle-upon-Tyne Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sleep Study	Assessment by polysomnography and maintenance of wakefulness test (MWT)	9-12 months
Other	Skeletal Muscle MRI of the lower extremities	Three imaging scans will be acquired of the lower extremities: T1-weighted images, TIRM images and Dixon images.	9-12 months
Primary	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	Cognitive assessment	These questionnaires include: Mini-Mental State Examination (MMS); Trail Making Test (TMT); Apathy Evaluation Scale (AES)	9-12 months
Secondary	Quality of Life using patient-reported outcomes	These questionnaires include: Individualised Neuromuscular Quality Of Life (InQoL); Myotonic Dystrophy Health Index (MDHI)	9-12 months
Secondary	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
Secondary	Pain assessment using patient-reported outcomes	These questionnaires include: McGill questionnaire; IVR Scale	9-12 months
Secondary	Blood and Urine collection for genetic and molecular biomarker analysis	Collection of: RNA, DNA, Serum and Urine	9-12 months
Secondary	Blood collection for Glycated Haemoglobin (HbA1c), Thyroid hormones, Androgens (in males only) analysis		9-12 months