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

• ClinicalTrials.gov Identifier: NCT02729597
• Recruitment Status: Completed
• First Posted: April 6, 2016
• Last Update Posted: April 6, 2016
• Sponsor: University Hospital, Bonn
• Collaborators: Forschungszentrum Juelich; Life and Brain Center Bonn; The Marigold Foundation
• Information provided by (Responsible Party): Cornelia Kornblum, University Hospital, Bonn

Tracking Information

• First Submitted Date: March 23, 2016
• First Posted Date: April 6, 2016
• Last Update Posted Date: April 6, 2016
• Study Start Date: May 2007
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2016)

• 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 Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 5, 2016)

• 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 baseline and after 5 years at follow-up ]
  The block design test consists of 9 blocks and 9 pictures. The study participant needs to look at the picture and reconstruct each picture by arranging all 9 blocks. Data measurement: time
• Phonematic fluency. Phonemic verbal word fluency is assessed using the oral word-fluency test, subtest 6 of the "Leistungsprüfsystem"; Horn, 1983. [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
  In a given time (one minute) the study participant needs to list as many words that begin with a certain letter. Data measurement: number of correct words
• Semantic fluency. Semantic word fluency is assessed using a test by Strauss et al.,2006. [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
  A certain category is provided and in a given time (one minute) the study participant needs to list as many items belonging to that category. Data measurement: number of correct items
• Daytime Sleepiness Scale (DSS) [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
• Krupp's Fatigue Severity Scale (KFSS) [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
• Epworth Sleepiness Scale (ESS) [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
• Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: First analysis at baseline and after 5 years at follow-up ]
• Ullanlinna-Narcolepsy Scale (UNS) [ Time Frame: First analysis at baseline and after 5 years at follow-up ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Tracking the Brain in Myotonic Dystrophies: a 5-year Longitudinal Follow-up Study
• 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 Description: 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.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients with genetically proven myotonic dystrophy type 1 and myotonic dystrophy type 2 and healthy controls

Condition

• Myotonic Dystrophy 1
• Myotonic Dystrophy 2

Intervention

• Other: medical history
  The complete medical history (including cardiovascular risk factors and medication) will be assessed at baseline and follow-up.
• Other: neurological clinical examination
  Neurological examination will be performed at baseline and follow-up.
• Other: neuropsychological testing
  Neuropsychological testing using a 13 item test battery will be performed at baseline and follow-up.
• Other: brain MRI
  Brain MRI ( 3.0 T) will be performed using the same hard- and software at baseline and follow-up.

Study Groups/Cohorts

• Myotonic dystrophy type 1 patients

  Patients with myotonic dystrophy type 1 (diagnosis confirmed by genetic testing) who meet all inclusion and exclusion criteria for patients.

  To be assessed at baseline and follow-up:

  medical history, neurological clinical examination, neuropsychological testing, brain MRI

  Interventions:

  • Other: medical history
  • Other: neurological clinical examination
  • Other: neuropsychological testing
  • Other: brain MRI
• Myotonic dystrophy type 2 patients

  Patients with myotonic dystrophy type 2 (diagnosis confirmed by genetic testing) who meet all inclusion and exclusion criteria for patients.

  To be assessed at baseline and follow-up:

  medical history, neurological clinical examination, neuropsychological testing, brain MRI

  Interventions:

  • Other: medical history
  • Other: neurological clinical examination
  • Other: neuropsychological testing
  • Other: brain MRI
• Controls

  Healthy control subjects who meet all inclusion and exclusion criteria for healthy controls.

  To be assessed at baseline and follow-up:

  medical history, neurological clinical examination, neuropsychological testing, brain MRI

  Interventions:

  • Other: medical history
  • Other: neurological clinical examination
  • Other: neuropsychological testing
  • Other: brain MRI

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 5, 2016): 49
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria for healthy controls:

• written informed consent
• normal neurological examination without any acute or former neurological or severe psychiatric disease, no medical history of traumatic brain injury

Inclusion criteria for patients:

• written informed consent
• diagnosis confirmed by genetic testing
• no other neurological or severe psychiatric disease, no medical history of traumatic brain injury

Exclusion criteria for healthy controls and patients:

• use of psychoactive substances including alcohol (except nicotine), formerly or currently; treatment with modafinil
• severe psychiatric disorders, serious physical illnesses, particularly cardiovascular diseases, formerly or currently
• non-removable ferromagnetic metallic implants, sensors, stimulators, prostheses, pacemaker, large tattoos
• claustrophobia
• age under 18 years

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02729597
• Other Study ID Numbers: DM-1-2
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Cornelia Kornblum, University Hospital, Bonn
• Study Sponsor: University Hospital, Bonn

Collaborators

• Forschungszentrum Juelich
• Life and Brain Center Bonn
• The Marigold Foundation

Investigators

• Study Chair: Cornelia Kornblum, Prof. Dr.; Department of Neurology, University Hospital of Bonn, Bonn, Germany
• Study Chair: Bernd Weber, Prof. Dr.; Life and Brain Center, Department of NeuroCognition-Imaging, Bonn, Germany

• PRS Account: University Hospital, Bonn
• Verification Date: April 2016