Clinical Trial: PhenoDM1 (Myotonic Dystrophy Type 1 Natural History Study)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

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 Summary: 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.
Sponsor: Newcastle-upon-Tyne Hospitals NHS Trust

Current Primary Outcome: 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: Characterise DM1 disease presentation and progression using relevant clinical assessments of muscle strength and function. [ Time Frame: 9-12 months ]

Current Secondary Outcome:

  • 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:

  • 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 ]


Information By: Newcastle-upon-Tyne Hospitals NHS Trust

Dates:
Date Received: March 22, 2016
Date Started: August 2015
Date Completion: October 31, 2018
Last Updated: March 29, 2017
Last Verified: March 2017