Clinical trial NCT02729597: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myotonic Dystrophy 1
Myotonic Dystrophy 2
Keywords: neuromuscular disorders
MRI
white matter
brain
myotonic dystrophy
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
Collaborators: name: Forschungszentrum Juelich
name: Life and Brain Center Bonn
name: The Marigold Foundation
First posted: 2016-04-06
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with genetically proven myotonic dystrophy type 1 and myotonic dystrophy type 2 and healthy controls

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.

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

Primary outcomes:
measure: Change in diffusivity indices as assessed by brain MRI with diffusion tensor imaging (DTI) sequences
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Gray matter changes assessed by magnetic resonance imaging (MRI)-voxel-based morphometry (VBM)
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Quantification of white matter lesions using age-related white matter changes (ARWMC) rating scale
timeFrame: First analysis at baseline and after 5 years at follow-up
Secondary outcomes:
measure: MIRS (Muscular impairment rating scale)
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Motor performance (Purdue Pegboard, bimanual)
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Beck Depression Inventory (BDI)
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Boston Naming Test
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Verbal memory recognition task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Figural memory recognition task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: 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)).
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Psychomotoric Speed. Psychomotoric speed is assessed using the Trail-Making Test, TMT A (Reitan, 1958).
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Reaction time, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Selective attention (Choice reaction time), a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Interference. Interference is analysed using two tasks.
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Attention shift. Attentional shift is analysed using the the Trail-Making Test, TMT B (Reitan, 1958).
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: 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).
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Phonematic fluency. Phonemic verbal word fluency is assessed using the oral word-fluency test, subtest 6 of the "Leistungsprüfsystem"; Horn, 1983.
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Semantic fluency. Semantic word fluency is assessed using a test by Strauss et al.,2006.
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Daytime Sleepiness Scale (DSS)
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Krupp's Fatigue Severity Scale (KFSS)
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Epworth Sleepiness Scale (ESS)
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: First analysis at baseline and after 5 years at follow-up
measure: Ullanlinna-Narcolepsy Scale (UNS)
timeFrame: First analysis at baseline and after 5 years at follow-up
Other outcomes:
Locations:
Study officials:
affiliation: Department of Neurology, University Hospital of Bonn, Bonn, Germany
name: Cornelia Kornblum, Prof. Dr.
role: STUDY_CHAIR
affiliation: Life and Brain Center, Department of NeuroCognition-Imaging, Bonn, Germany
name: Bernd Weber, Prof. Dr.
role: STUDY_CHAIR
References: