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PhenoDM1 (Myotonic Dystrophy Type 1 Natural History Study) (PhenoDM1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02831504
Recruitment Status : Completed
First Posted : July 13, 2016
Last Update Posted : April 13, 2021
Information provided by (Responsible Party):
Newcastle-upon-Tyne Hospitals NHS Trust

Tracking Information
First Submitted Date March 22, 2016
First Posted Date July 13, 2016
Last Update Posted Date April 13, 2021
Actual Study Start Date August 2015
Actual Primary Completion Date October 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 20, 2016)
Strength and function [ Time Frame: 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)
Original Primary Outcome Measures
 (submitted: July 8, 2016)
Characterise DM1 disease presentation and progression using relevant clinical assessments of muscle strength and function. [ Time Frame: 9-12 months ]
Change History
Current Secondary Outcome Measures
 (submitted: July 20, 2016)
  • Cognitive assessment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 9-12 months ]
    These questionnaires include:
    • Checklist Individual Strength
    • Epworth Sleepiness Scale
    • Fatigue and Daytime Sleepiness Scale
  • Pain assessment using patient-reported outcomes [ Time Frame: 9-12 months ]
    These questionnaires include:
    • McGill questionnaire
    • IVR Scale
  • Blood and Urine collection for genetic and molecular biomarker analysis [ Time Frame: 9-12 months ]
    Collection of: RNA, DNA, Serum and Urine
  • Blood collection for Glycated Haemoglobin (HbA1c), Thyroid hormones, Androgens (in males only) analysis [ Time Frame: 9-12 months ]
Original Secondary Outcome Measures
 (submitted: July 8, 2016)
  • Obtain information to better characterise the quality of life of the DM1 patients using patient-reported outcomes. [ Time Frame: 9-12 months ]
  • Identify biomarkers and efficacy measures for use in future clinical trials. [ Time Frame: 9-12 months ]
Current Other Pre-specified Outcome Measures
 (submitted: July 20, 2016)
  • Sleep Study [ Time Frame: 9-12 months ]
    Assessment by polysomnography and maintenance of wakefulness test (MWT)
  • Skeletal Muscle MRI of the lower extremities [ Time Frame: 9-12 months ]
    Three imaging scans will be acquired of the lower extremities: T1-weighted images, TIRM images and Dixon images.
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title 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
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.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
All blood and urine will be processed and stored in Newcastle Biobank for Research of Neuromuscular Disorders (Newcastle and North Tyneside 1 -REF/08/H0906/28).
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.

Condition Myotonic Dystrophy Type 1
Intervention Not Provided
Study Groups/Cohorts Myotonic Dystrophy type 1 (DM1) patients
Natural History Study
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: March 27, 2018)
Original Estimated Enrollment
 (submitted: July 8, 2016)
Actual Study Completion Date October 31, 2018
Actual Primary Completion Date October 31, 2018   (Final data collection date for primary outcome measure)
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
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United Kingdom
Removed Location Countries  
Administrative Information
NCT Number NCT02831504
Other Study ID Numbers 7491
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Yes
Responsible Party Newcastle-upon-Tyne Hospitals NHS Trust
Study Sponsor Newcastle-upon-Tyne Hospitals NHS Trust
Collaborators Not Provided
Principal Investigator: Hanns Lochmuller, MD, FAAN University of Newcastle Upon-Tyne
Principal Investigator: Chris Turner, FRCP, PhD National Hospital for Neurology and Neurosurgery
PRS Account Newcastle-upon-Tyne Hospitals NHS Trust
Verification Date April 2021