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

Myotonic Dystrophy 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02729597
• Other study ID #: DM-1-2
• Status: Completed
• Phase: N/A
• First received: March 23, 2016
• Last updated: April 5, 2016
• Start date: May 2007
• Est. completion date: August 2015

Study information

• Verified date: April 2016
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ministry of Health
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: August 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Myotonic Dystrophy
• 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.
• neurological clinical examination
Neurological examination will be performed at baseline and follow-up.
• neuropsychological testing
Neuropsychological testing using a 13 item test battery will be performed at baseline and follow-up.
• brain MRI
Brain MRI ( 3.0 T) will be performed using the same hard- and software at baseline and follow-up.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Bonn	Forschungszentrum Juelich, Life and Brain Center Bonn, The Marigold Foundation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in diffusivity indices as assessed by brain MRI with diffusion tensor imaging (DTI) sequences		First analysis at baseline and after 5 years at follow-up	No
Primary	Gray matter changes assessed by magnetic resonance imaging (MRI)-voxel-based morphometry (VBM)		First analysis at baseline and after 5 years at follow-up	No
Primary	Quantification of white matter lesions using age-related white matter changes (ARWMC) rating scale		First analysis at baseline and after 5 years at follow-up	No
Secondary	MIRS (Muscular impairment rating scale)	Rating scale to assess disease severity in myotonic dystrophy type 1 patients	First analysis at baseline and after 5 years at follow-up	No
Secondary	Motor performance (Purdue Pegboard, bimanual)	A bimanual task to assess fine motor function in patients and controls. Results are used as a covariate for neuropsychological tests	First analysis at baseline and after 5 years at follow-up	No
Secondary	Beck Depression Inventory (BDI)	To assess depressive symptoms	First analysis at baseline and after 5 years at follow-up	No
Secondary	Boston Naming Test	A test to evaluate semantic memory.	First analysis at baseline and after 5 years at follow-up	No
Secondary	Verbal memory recognition task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).	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	First analysis at baseline and after 5 years at follow-up	No
Secondary	Figural memory recognition task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).	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	First analysis at baseline and after 5 years at follow-up	No
Secondary	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)).	Data measurement: time	First analysis at baseline and after 5 years at follow-up	No
Secondary	Psychomotoric Speed. Psychomotoric speed is assessed using the Trail-Making Test, TMT A (Reitan, 1958).	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	First analysis at baseline and after 5 years at follow-up	No
Secondary	Reaction time, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).	Data measurement: time	First analysis at baseline and after 5 years at follow-up	No
Secondary	Selective attention (Choice reaction time), a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).	Data measurement: time	First analysis at baseline and after 5 years at follow-up	No
Secondary	Interference. Interference is analysed using two tasks.	Response inhibition subtest of the "Cerebraler Insuffizienztest" (c.I.T.I; Lehrl and Fischer, 1997).; 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	First analysis at baseline and after 5 years at follow-up	No
Secondary	Attention shift. Attentional shift is analysed using the the Trail-Making Test, TMT B (Reitan, 1958).	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	First analysis at baseline and after 5 years at follow-up	No
Secondary	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).	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	First analysis at baseline and after 5 years at follow-up	No
Secondary	Phonematic fluency. Phonemic verbal word fluency is assessed using the oral word-fluency test, subtest 6 of the "Leistungsprüfsystem"; Horn, 1983.	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	First analysis at baseline and after 5 years at follow-up	No
Secondary	Semantic fluency. Semantic word fluency is assessed using a test by Strauss et al.,2006.	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	First analysis at baseline and after 5 years at follow-up	No
Secondary	Daytime Sleepiness Scale (DSS)		First analysis at baseline and after 5 years at follow-up	No
Secondary	Krupp's Fatigue Severity Scale (KFSS)		First analysis at baseline and after 5 years at follow-up	No
Secondary	Epworth Sleepiness Scale (ESS)		First analysis at baseline and after 5 years at follow-up	No
Secondary	Pittsburgh Sleep Quality Index (PSQI)		First analysis at baseline and after 5 years at follow-up	No
Secondary	Ullanlinna-Narcolepsy Scale (UNS)		First analysis at baseline and after 5 years at follow-up	No