Clinical Trial: Tracking the Brain in Myotonic Dystrophies: a 5-year Longitudinal Follow-up Study

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Tracking the Brain in Myotonic Dystrophies: a 5-year Longitudinal Follow-up Study

Brief Summary: The natural history of brain affection in myotonic dystrophy types 1 and 2 is still unknown. The investigators designed a 5-year longitudinal neuropsychological and neuroimaging follow-up study to address this issue. Myotonic dystrophy type 1, myotonic dystrophy type 2 patients, and healthy controls were enrolled. All participants undergo clinical-neurological examinations, neuropsychological analyses according to a 13-item neuropsychological test battery, and 3T-brain MRI including voxel-based morphometry and diffusion tensor imaging at baseline and at follow-up using identical examination protocols.

Detailed Summary: It is unknown whether brain affection in myotonic dystrophy types 1 and 2 is due to neurodevelopmental defects, neurodegeneration, or both. An exact definition of the nature and dynamic of brain affection is of urgent need for the identification of clinical trial outcome parameters and the design of therapy compounds. The investigators planned a 5-year longitudinal study to examine the natural history of functional and structural brain affection. Myotonic dystrophy type 1, myotonic dystrophy type 2 patients, and healthy controls were enrolled. All participants undergo clinical-neurological examinations, neuropsychological analyses according to a 13-item neuropsychological test battery, and 3T-brain MRI at baseline and at follow-up using identical examination protocols. The intended time span between baseline and follow-up examinations is 5 years minimum. To investigate gray and white matter affection, voxel-based morphometry and diffusion tensor imaging are performed, and data are statistically analyzed including (i) group comparisons between patients and controls at baseline and follow-up, and (ii) group comparisons using difference maps to focus on isolated disease-related effects over time.
Sponsor: University Hospital, Bonn

Current Primary Outcome:

  • Change in diffusivity indices as assessed by brain MRI with diffusion tensor imaging (DTI) sequences [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
  • Gray matter changes assessed by magnetic resonance imaging (MRI)-voxel-based morphometry (VBM) [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
  • Quantification of white matter lesions using age-related white matter changes (ARWMC) rating scale [ Time Frame: First analysis at baseline and after 5 years at follow-up ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • MIRS (Muscular impairment rating scale) [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
    Rating scale to assess disease severity in myotonic dystrophy type 1 patients
  • Motor performance (Purdue Pegboard, bimanual) [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
    A bimanual task to assess fine motor function in patients and controls. Results are used as a covariate for neuropsychological tests
  • Beck Depression Inventory (BDI) [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
    To assess depressive symptoms
  • Boston Naming Test [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
    A test to evaluate semantic memory.
  • Verbal memory recognition task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006). [ Time Frame: First analysis at baseline and after 5 years at follow-up ]

    Word list learning: 3 repetitions of word list presentation, 12 words. Yes/No recognition test (items:distractors 1 : 2) (reaction intervall: 2 seconds).

    Data measurement: reaction time, number of correct hits

  • Figural memory recognition task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006). [ Time Frame: First analysis at baseline and after 5 years at follow-up ]

    Figural pattern learning: 12 different checkerboard patterns are presented, 3 repetitions of checkboard pattern presentation. Checkerboard consists of 3x3 fields, each pattern consists of 4 highlighted fields. Yes/No recognition test (items:distractors 1 : 2) (reaction interval: 2 seconds).

    Data measurement: reaction time, number of correct hits

  • Focussed Attention. Focussed attention concerning processing speed is assessed with a symbol-counting task (subtest 1 of the "Cerebraler Insuffizienztest", c.I.T.S. (Lehrl, 1997)). [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
    Data measurement: time
  • Psychomotoric Speed. Psychomotoric speed is assessed using the Trail-Making Test, TMT A (Reitan, 1958). [ Time Frame: First analysis at baseline and after 5 years at follow-up ]

    The TMT-A test consists of 25 numbered circles randomly distributed over a sheet of paper. The study participant needs to draw lines to connect the numbers in ascending order.

    Data measurement: time

  • Reaction time, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006). [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
    Data measurement: time
  • Selective attention (Choice reaction time), a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006). [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
    Data measurement: time
  • Interference. Interference is analysed using two tasks. [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
    1. Response inhibition subtest of the "Cerebraler Insuffizienztest" (c.I.T.I; Lehrl and Fischer, 1997).
    2. Inverted choice reaction with reversed conditions of a choice reaction task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).

    Data measurement: reaction time

  • Attention shift. Attentional shift is analysed using the the Trail-Making Test, TMT B (Reitan, 1958). [ Time Frame: First analysis at baseline and after 5 years at follow-up ]

    The TMT B test consists of 25 circles randomly distributed over a sheet of paper. These circles include both numbers and letters. The study participant needs to draw lines to connect the numbers and letters in an ascending order, but alternating between numbers and letters.

    Data measurement: time

  • Visual-spatial / visual-constructive abilities. Visual-spatial / visual-constructive abilities are investigated using the Block design Test (part of "Hamburg-Wechsler Intelligenztest für Erwachsene"—Revision (HAWIE-R); Tewes, 1991). [ Time Frame: First analysis at basel

    Original Secondary Outcome: Same as current

    Information By: University Hospital, Bonn

    Dates:
    Date Received: March 23, 2016
    Date Started: May 2007
    Date Completion:
    Last Updated: April 5, 2016
    Last Verified: April 2016