Clinical trial NCT02831504: PhenoDM1 (Myotonic Dystrophy Type 1 Natural History Study)
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myotonic Dystrophy Type 1
Keywords: Myotonic Dystrophy type 1
DM1
Muscular Dystrophy
Neuromuscular Diseases
Lead sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor class: OTHER
First posted: 2016-07-13
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Inclusion criteria will be limited to those over 18 years of age, with a genetic confirmation of DM1 who are able to provide informed consent. This unrestrictive approach will enable assessment of a true cross-section of the population, including those with congenital, childhood and adult onset. Two substudies will be open to a subset of patients, one assessing muscle through MRI and on focussing on sleep and fatigue. Additional restrictions may be in place to ensure the safety of the participants during these studies.

Informed consent will be obtained from all patients, including detailed patient information. Sharing and storage of data and samples will be discussed in this information and covered appropriately in the consent.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Strength and function
timeFrame: 9-12 months
Secondary outcomes:
measure: Cognitive assessment
timeFrame: 9-12 months
measure: Quality of Life using patient-reported outcomes
timeFrame: 9-12 months
measure: Fatigue and Daytime Sleepiness assessment using patient-reported outcomes
timeFrame: 9-12 months
measure: Pain assessment using patient-reported outcomes
timeFrame: 9-12 months
measure: Blood and Urine collection for genetic and molecular biomarker analysis
timeFrame: 9-12 months
measure: Blood collection for Glycated Haemoglobin (HbA1c), Thyroid hormones, Androgens (in males only) analysis
timeFrame: 9-12 months
Other outcomes:
measure: Sleep Study
timeFrame: 9-12 months
measure: Skeletal Muscle MRI of the lower extremities
timeFrame: 9-12 months
Locations:
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle-upon-Tyne Hospitals NHS Trust
state: Tyne And Wear
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust, National Hospital for Neurology and Neurosurgery
Study officials:
affiliation: University of Newcastle Upon-Tyne
name: Hanns Lochmuller, MD, FAAN
role: PRINCIPAL_INVESTIGATOR
affiliation: National Hospital for Neurology and Neurosurgery
name: Chris Turner, FRCP, PhD
role: PRINCIPAL_INVESTIGATOR
References: