Myotonic Dystrophy 1NCT02729597
Tracking the Brain in Myotonic Dystrophies: a 5-year Longitudinal Follow-up Study
An observational study of Myotonic Dystrophy 1 and Myotonic Dystrophy 2, run by University Hospital, Bonn.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Myotonic Dystrophy 1, Myotonic Dystrophy 2
- What is being tested?
- medical history, neurological clinical examination and neuropsychological testing
- How many people
- 49 participants
- Where
- No sites listed yet
- Study dates
- May 2007to Aug 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with genetically proven myotonic dystrophy type 1 and myotonic dystrophy type 2 and healthy controls
Who may be able to join
- written informed consent
- normal neurological examination without any acute or former neurological or severe psychiatric disease, no medical history of traumatic brain injury
- written informed consent
- diagnosis confirmed by genetic testing
- no other neurological or severe psychiatric disease, no medical history of traumatic brain injury
Who cannot join
- 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
About this study
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.
Read the 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.
- Conditions
- Myotonic Dystrophy 1, Myotonic Dystrophy 2
- Being tested
- medical history, neurological clinical examination, neuropsychological testing, brain MRI
- Keywords
- neuromuscular disorders, MRI, white matter, brain, myotonic dystrophy
- Medical subject headings
- Myotonic Dystrophy, Neuromuscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
medical historyOther
The complete medical history (including cardiovascular risk factors and medication) will be assessed at baseline and follow-up.
neurological clinical examinationOther
Neurological examination will be performed at baseline and follow-up.
neuropsychological testingOther
Neuropsychological testing using a 13 item test battery will be performed at baseline and follow-up.
brain MRIOther
Brain MRI ( 3.0 T) will be performed using the same hard- and software at baseline and follow-up.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Other: medical history; Other: neurological clinical examination; Other: neuropsychological testing; Other: brain MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in diffusivity indices as assessed by brain MRI with diffusion tensor imaging (DTI) sequences
Measured: First analysis at baseline and after 5 years at follow-up
Gray matter changes assessed by magnetic resonance imaging (MRI)-voxel-based morphometry (VBM)
Measured: 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
Measured: First analysis at baseline and after 5 years at follow-up
Secondary outcomes (20)
MIRS (Muscular impairment rating scale)
Rating scale to assess disease severity in myotonic dystrophy type 1 patients
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
Beck Depression Inventory (BDI)
To assess depressive symptoms
Measured: First analysis at baseline and after 5 years at follow-up
Boston Naming Test
A test to evaluate semantic memory.
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
Reaction time, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).
Data measurement: time
Measured: First analysis at baseline and after 5 years at follow-up
Selective attention (Choice reaction time), a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006).
Data measurement: time
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
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
Measured: First analysis at baseline and after 5 years at follow-up
Daytime Sleepiness Scale (DSS)
Measured: First analysis at baseline and after 5 years at follow-up
Krupp's Fatigue Severity Scale (KFSS)
Measured: First analysis at baseline and after 5 years at follow-up
Epworth Sleepiness Scale (ESS)
Measured: First analysis at baseline and after 5 years at follow-up
Pittsburgh Sleep Quality Index (PSQI)
Measured: First analysis at baseline and after 5 years at follow-up
Ullanlinna-Narcolepsy Scale (UNS)
Measured: First analysis at baseline and after 5 years at follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study startMay 2007
- Primary completionDec 2014
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myotonic Dystrophy 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bonn
- Sponsor type
- University, hospital or other
- Collaborators
- Forschungszentrum Juelich, Life and Brain Center Bonn, The Marigold Foundation
- Responsible party
- Principal investigator, Cornelia Kornblum, University Hospital, Bonn
- Investigators
- Cornelia Kornblum, Prof. Dr., Study chair, Department of Neurology, University Hospital of Bonn, Bonn, GermanyBernd Weber, Prof. Dr., Study chair, Life and Brain Center, Department of NeuroCognition-Imaging, Bonn, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02729597
- Sponsor's protocol ID
- DM-1-2
- Status last verified
- Apr 2016
- First submitted
- 23 Mar 2016
- Last updated
- 6 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tracking the Brain in Myotonic Dystrophies: a 5-year Longitudinal Follow-up Study
- ClinicalTrials.gov ID
- NCT02729597
- Acronym / sponsor ID
- DM-1-2
- Conditions
- Myotonic Dystrophy 1, Myotonic Dystrophy 2
- Keywords
- neuromuscular disorders, MRI, white matter, brain, myotonic dystrophy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University Hospital, BonnUniversity, hospital or other
- Collaborators
- Forschungszentrum Juelich, Life and Brain Center Bonn, The Marigold Foundation
- Study start
- May 2007
- Primary completion
- Dec 2014 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 6 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Myotonic dystrophy type 1 patients | – | Other: medical history, Other: neurological clinical examination, Other: neuropsychological testing, Other: brain MRIPatients 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 |
| Myotonic dystrophy type 2 patients | – | Other: medical history, Other: neurological clinical examination, Other: neuropsychological testing, Other: brain MRIPatients 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 |
| Controls | – | Other: medical history, Other: neurological clinical examination, Other: neuropsychological testing, Other: brain MRIHealthy 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with genetically proven myotonic dystrophy type 1 and myotonic dystrophy type 2 and healthy controls
Key inclusion criteria (5 listed)
- written informed consent
- normal neurological examination without any acute or former neurological or severe psychiatric disease, no medical history of traumatic brain injury
- written informed consent
- diagnosis confirmed by genetic testing
- no other neurological or severe psychiatric disease, no medical history of traumatic brain injury
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| medical historyThe complete medical history (including cardiovascular risk factors and medication) will be assessed at baseline and follow-up. | Other | Controls, Myotonic dystrophy type 1 patients, Myotonic dystrophy type 2 patients |
| neurological clinical examinationNeurological examination will be performed at baseline and follow-up. | Other | Controls, Myotonic dystrophy type 1 patients, Myotonic dystrophy type 2 patients |
| neuropsychological testingNeuropsychological testing using a 13 item test battery will be performed at baseline and follow-up. | Other | Controls, Myotonic dystrophy type 1 patients, Myotonic dystrophy type 2 patients |
| brain MRIBrain MRI ( 3.0 T) will be performed using the same hard- and software at baseline and follow-up. | Other | Controls, Myotonic dystrophy type 1 patients, Myotonic dystrophy type 2 patients |
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
20 secondary outcomes
MIRS (Muscular impairment rating scale)
Time frame: First analysis at baseline and after 5 years at follow-up
Motor performance (Purdue Pegboard, bimanual)
Time frame: First analysis at baseline and after 5 years at follow-up
Beck Depression Inventory (BDI)
Time frame: First analysis at baseline and after 5 years at follow-up
Boston Naming Test
Time frame: First analysis at baseline and after 5 years at follow-up
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
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
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
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
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
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
Interference. Interference is analysed using two tasks.
Time frame: First analysis at baseline and after 5 years at follow-up
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
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2016.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cornelia Kornblum, Prof. Dr. study chair
Department of Neurology, University Hospital of Bonn, Bonn, Germany
Bernd Weber, Prof. Dr. study chair
Life and Brain Center, Department of NeuroCognition-Imaging, Bonn, Germany
Questions about this trial
What is this clinical trial studying?
An observational study of Myotonic Dystrophy 1 and Myotonic Dystrophy 2, run by University Hospital, Bonn.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2016.