Parkinson DiseaseNCT02288052
Consolidation of Motor Learning of Writing Skills and Its Related Brain Activity Changes in Parkinson's Disease
A study testing Writing program and Stretch & Relaxation program in people with Parkinson Disease, run by KU Leuven at 1 site in Belgium.
Trial summary
The basal ganglia play an important role in motor learning, especially during the consolidation phase of motor learning. This raises the question whether it is possible to sustain learning increments in a neurodegenerative condition such as Parkinson's disease (PD). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Writing program and Stretch & Relaxation program
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteBelgium
- Study dates
- Jan 2013to Jan 2016
- Phase
- Interventional
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of PD based on the UK Brain Bank criteria
- Hoehn \& Yahr stage I (with impairments on the right side) and II in the on-phase
- Without cognitive impairment (MMSE >24)
- On stable medication
- Right handed
Who cannot join
- Deep Brain Stimulator
- Other contra-indications for MR scanning
- Colorblind
Trial locations and contacts
1 site in 1 country.
About this study
The basal ganglia play an important role in motor learning, especially during the consolidation phase of motor learning. This raises the question whether it is possible to sustain learning increments in a neurodegenerative condition such as Parkinson's disease (PD). The aim of this study is to gain knowledge on whether it is possible to relearn skills which are actually affected by PD, such as writing, and determine whether neuroplasticity is possible. In this randomized controlled study, PD patients will either follow intensive writing training or a placebo treatment (stretch and relaxation training) during 6 weeks. The writing training will focus on automatization (withstanding dual task interference), transfer to an untrained task and retention. The placebo program is aimed to reduce stiffness in the upper limbs and has been shown to be ineffective in PD. To date, it is unknown how neural networks change as a result of consolidation after a prolonged period of motor learning in PD. Therefore the second arm of this study will investigate, for the first time, changes in neural connectivity using brain imaging data to elucidate which neuroanatomical regions are involved in consolidation of learning in PD. Finally, DTI and resting state fMRI-analysis will complement insights into the neural changes as a result of learning.
Read the detailed description
This translational study is a monocentric Randomized Controlled Trial (RCT). The investigators will recruit 40 PD patients from the early Hoehn \& Yahr stages. Patients will be randomly allocated to an experimental group (writing training) and a control group (stretch- and relaxation training). All patients will receive the same frequency and duration of intervention. After the training period, patients will be followed up for another 6 weeks. Patients will be tested in the ON-phase of the medication cycle at 3 occasions: before (T1) and after training (T2) and after a 6-week retention period (T3). At T1 \& T2 participants will be tested at the behavioral \& neural level. At T3 participants will only be tested at the behavioral level.
Motor performance will be measured using MRI-compatible touch sensitive tablets and pencils. This system allows registration and translation of writing movements into online-cursor movements on screen in and outside a scanner environment. Both patient groups will be compared during a behavioral test battery consisting of (i) a trained sequence with and without visual cues; (ii) an untrained sequence with and without visual cues to test transfer; and (iii) a trained dual task to test automatization. Visual cues will consist of differently colored target zones of different band widths, indicating the scale and accuracy of writing.
Functional MRI measurements will take place in a 3T MR Philips Intera scanner. Before scanning, subjects will undergo a training session in a dummy scanner to familiarize them with the scanner environment and task instructions. During the fMRI sessions, participants will perform a trained and untrained sequence, both with and without visual cues. To control for differences in movement speed, all participants will perform the tasks at the same frequency, defined by an auditory pace. In addition to the fMRI measurements, resting state fMRI and DTI will also be performed to reveal alterations of the structural and functional connectivity between critical regions.
Behavioral data will be recorded as xy-coordinates and pressure values at a sampling rate of 200Hz and with a spatial resolution of 32.5µm. Statistical analysis of the behavioral data will have a between-subject factor of group (experimental and placebo group) and a within-subject factor of time (before training, after training and after the retention period).
Image analysis will be performed with Statistical Parametric Mapping (SPM) software. The investigators will contrast for either decreased or increased activation, as different regions may show divergent changes related to learning and transfer, with group as a between-subject factor and time (before and after training) and task condition (trained with cues, trained without cues, untrained with cues and untrained without cues) as within-subject factors.
- Conditions
- Parkinson Disease
- Being tested
- Writing program, Stretch & Relaxation program
- Keywords
- Handwriting, Motor learning
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Writing programBehavioural
6 weeks of at-home training (5days/week, 30minutes/day) using both pen-and-paper exercises and exercises on a writing tablet.
Stretch & Relaxation programBehavioural
6 weeks of at-home training (5days/week, 30minutes/day) using a DVD with exercises.
| Study group | Role | What they receive |
|---|---|---|
| Writing program | Experimental | The program will train participants in maintaining writing amplitude, writing speed, writing fluently and automatization of writing. Receives: Behavioral: Writing program |
| Stretch & Relaxation program | Placebo comparator | The program will learn participants to alleviate tension in the upper limbs and will consist of exercises performed while lying down or sitting. Receives: Behavioral: Stretch & Relaxation program |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in writing amplitude (cm) on tablet after 6 weeks of training
Analysis based on measurement of XYZ coordinates, measured at a spatial resolution of 32.5 μm.
Measured: 6 weeks
Change from baseline in writing amplitude (cm) on tablet after 12 weeks, including 6 weeks without training
Analysis based on measurement of XYZ coordinates, measured at a spatial resolution of 32.5 μm.
Measured: 12 weeks
Change from baseline in brain activity during writing (functional MRI) after 6 weeks of training
Analysis of the change in Blood Oxygen Level Dependent (BOLD) response
Measured: 6 weeks
Change from baseline in brain activity during rest (resting state MRI) after 6 weeks of training
Analysis of the change in Blood Oxygen Level Dependent (BOLD) response
Measured: 6 weeks
Change from baseline in Diffusion Tensor Imaging after 6 weeks of training
Analysis of the change in Blood Oxygen Level Dependent (BOLD) response
Measured: 6 weeks
Secondary outcomes (12)
Transfer of change in writing amplitude to an untrained writing sequence after 6 weeks of training
Analysis based on measurement of XYZ coordinates, measured at a spatial resolution of 32.5 μm.
Measured: 6 weeks
Transfer of change in writing amplitude to an untrained writing sequence after 12 weeks, including 6 weeks without training
Analysis based on measurement of XYZ coordinates, measured at a spatial resolution of 32.5 μm.
Measured: 12 weeks
Change from baseline in dual task effect (DTE) for writing amplitude after 6 weeks of training
Analysis of the DTE using the following formula: DTE= ((dual task amplitude-single task amplitude)/(single task amplitude))*100
Measured: 6 weeks
Change from baseline in dual task effect (DTE) for writing amplitude after 12 weeks, including 6 weeks without training
Analysis of the DTE using the following formula: DTE= ((dual task amplitude-single task amplitude)/(single task amplitude))*100
Measured: 12 weeks
Change from baseline in writing fluency (normalized jerk) on tablet after 6 weeks of training
Analysis based on measurement of XYZ coordinates, measured at a spatial resolution of 32.5 μm.
Measured: 6 weeks
Change from baseline in writing fluency (normalized jerk) on tablet after 12 weeks, including 6 weeks without training
Analysis based on measurement of XYZ coordinates, measured at a spatial resolution of 32.5 μm.
Measured: 12 weeks
Systematic Screening of handwriting difficulties (writing on paper) - change from baseline in quality score after 6 weeks of training
Analysis of the quality of handwriting based on different criteria (fluency in letter formation, connections between letters, regularity of letter height, space between words and straightness of the sentence).
Measured: 6 weeks
Systematic Screening of handwriting difficulties (writing on paper) - change from baseline in quality score after 12 weeks, including 6 weeks without training
Analysis of the quality of handwriting based on different criteria (fluency in letter formation, connections between letters, regularity of letter height, space between words and straightness of the sentence).
Measured: 12 weeks
Systematic Screening of handwriting difficulties (writing on paper) - change from baseline in writing speed after 6 weeks of training
Analysis of the number of letters written within a period of 5 minutes.
Measured: 6 weeks
Systematic Screening of handwriting difficulties (writing on paper) - change from baseline in writing speed after 12 weeks, including 6 weeks without training
Analysis of the number of letters written within a period of 5 minutes.
Measured: 12 weeks
Change from baseline in Purdue Pegboard test after 6 weeks of training
Analysis of the number of pegs placed within 30s.
Measured: 6 weeks
Change from baseline in Purdue Pegboard test after 12 weeks, including 6 weeks without training
Analysis of the number of pegs placed within 30s.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2014 (estimated)
- Study startJan 2013
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by KU LeuvenThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- Research Foundation Flanders
- Responsible party
- Principal investigator, Alice Nieuwboer, KU Leuven
- Investigators
- Alice Nieuwboer, Professor, Principal investigator, KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02288052
- Sponsor's protocol ID
- G.0906.11
- Status last verified
- Jan 2016
- First submitted
- 3 Nov 2014
- Last updated
- 28 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Broeder S, Nackaerts E, Nieuwboer A, Smits-Engelsman BC, Swinnen SP, Heremans E. The effects of dual tasking on handwriting in patients with Parkinson's disease. Neuroscience. 2014 Mar 28;263:193-202. doi: 10.1016/j.neuroscience.2014.01.019. Epub 2014 Jan 19.
PubMed 24447597Nackaerts E, Vervoort G, Heremans E, Smits-Engelsman BC, Swinnen SP, Nieuwboer A. Relearning of writing skills in Parkinson's disease: a literature review on influential factors and optimal strategies. Neurosci Biobehav Rev. 2013 Mar;37(3):349-57. doi: 10.1016/j.neubiorev.2013.01.015. Epub 2013 Jan 16.
PubMed 23333265
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Consolidation of Motor Learning of Writing Skills and Its Related Brain Activity Changes in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT02288052
- Acronym / sponsor ID
- G.0906.11
- Conditions
- Parkinson Disease
- Keywords
- Handwriting, Motor learning
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- KU LeuvenUniversity, hospital or other
- Collaborators
- Research Foundation Flanders
- Study start
- Jan 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 11 Nov 2014 (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 basal ganglia play an important role in motor learning, especially during the consolidation phase of motor learning. This raises the question whether it is possible to sustain learning increments in a neurodegenerative condition such as Parkinson's disease (PD). The aim of this study is to gain knowledge on whether it is possible to relearn skills which are actually affected by PD, such as writing, and determine whether neuroplasticity is possible. In this randomized controlled study, PD patients will either follow intensive writing training or a placebo treatment (stretch and relaxation training) during 6 weeks. The writing training will focus on automatization (withstanding dual task interference), transfer to an untrained task and retention. The placebo program is aimed to reduce stiffness in the upper limbs and has been shown to be ineffective in PD. To date, it is unknown how neural networks change as a result of consolidation after a prolonged period of motor learning in PD. Therefore the second arm of this study will investigate, for the first time, changes in neural connectivity using brain imaging data to elucidate which neuroanatomical regions are involved in consolidation of learning in PD. Finally, DTI and resting state fMRI-analysis will complement insights into the neural changes as a result of learning.
Detailed description
This translational study is a monocentric Randomized Controlled Trial (RCT). The investigators will recruit 40 PD patients from the early Hoehn \& Yahr stages. Patients will be randomly allocated to an experimental group (writing training) and a control group (stretch- and relaxation training). All patients will receive the same frequency and duration of intervention. After the training period, patients will be followed up for another 6 weeks. Patients will be tested in the ON-phase of the medication cycle at 3 occasions: before (T1) and after training (T2) and after a 6-week retention period (T3). At T1 \& T2 participants will be tested at the behavioral \& neural level. At T3 participants will only be tested at the behavioral level.
Motor performance will be measured using MRI-compatible touch sensitive tablets and pencils. This system allows registration and translation of writing movements into online-cursor movements on screen in and outside a scanner environment. Both patient groups will be compared during a behavioral test battery consisting of (i) a trained sequence with and without visual cues; (ii) an untrained sequence with and without visual cues to test transfer; and (iii) a trained dual task to test automatization. Visual cues will consist of differently colored target zones of different band widths, indicating the scale and accuracy of writing.
Functional MRI measurements will take place in a 3T MR Philips Intera scanner. Before scanning, subjects will undergo a training session in a dummy scanner to familiarize them with the scanner environment and task instructions. During the fMRI sessions, participants will perform a trained and untrained sequence, both with and without visual cues. To control for differences in movement speed, all participants will perform the tasks at the same frequency, defined by an auditory pace. In addition to the fMRI measurements, resting state fMRI and DTI will also be performed to reveal alterations of the structural and functional connectivity between critical regions.
Behavioral data will be recorded as xy-coordinates and pressure values at a sampling rate of 200Hz and with a spatial resolution of 32.5µm. Statistical analysis of the behavioral data will have a between-subject factor of group (experimental and placebo group) and a within-subject factor of time (before training, after training and after the retention period).
Image analysis will be performed with Statistical Parametric Mapping (SPM) software. The investigators will contrast for either decreased or increased activation, as different regions may show divergent changes related to learning and transfer, with group as a between-subject factor and time (before and after training) and task condition (trained with cues, trained without cues, untrained with cues and untrained without cues) as within-subject factors.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Writing program | Experimental | Behavioral: Writing programThe program will train participants in maintaining writing amplitude, writing speed, writing fluently and automatization of writing. |
| Stretch & Relaxation program | Placebo comparator | Behavioral: Stretch & Relaxation programThe program will learn participants to alleviate tension in the upper limbs and will consist of exercises performed while lying down or sitting. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of PD based on the UK Brain Bank criteria
- Hoehn \& Yahr stage I (with impairments on the right side) and II in the on-phase
- Without cognitive impairment (MMSE >24)
- On stable medication
- Right handed
Key exclusion criteria (3 listed)
- Deep Brain Stimulator
- Other contra-indications for MR scanning
- Colorblind
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 |
|---|---|---|
| Writing program6 weeks of at-home training (5days/week, 30minutes/day) using both pen-and-paper exercises and exercises on a writing tablet. | Behavioural | Writing program |
| Stretch & Relaxation program6 weeks of at-home training (5days/week, 30minutes/day) using a DVD with exercises. | Behavioural | Stretch & Relaxation program |
Primary outcome
Change from baseline in writing amplitude (cm) on tablet after 6 weeks of training
Time frame: 6 weeks
Analysis based on measurement of XYZ coordinates, measured at a spatial resolution of 32.5 μm.
Change from baseline in writing amplitude (cm) on tablet after 12 weeks, including 6 weeks without training
Time frame: 12 weeks
Analysis based on measurement of XYZ coordinates, measured at a spatial resolution of 32.5 μm.
Change from baseline in brain activity during writing (functional MRI) after 6 weeks of training
Time frame: 6 weeks
Analysis of the change in Blood Oxygen Level Dependent (BOLD) response
Change from baseline in brain activity during rest (resting state MRI) after 6 weeks of training
Time frame: 6 weeks
Analysis of the change in Blood Oxygen Level Dependent (BOLD) response
Change from baseline in Diffusion Tensor Imaging after 6 weeks of training
Time frame: 6 weeks
Analysis of the change in Blood Oxygen Level Dependent (BOLD) response
12 secondary outcomes
Transfer of change in writing amplitude to an untrained writing sequence after 6 weeks of training
Time frame: 6 weeks
Transfer of change in writing amplitude to an untrained writing sequence after 12 weeks, including 6 weeks without training
Time frame: 12 weeks
Change from baseline in dual task effect (DTE) for writing amplitude after 6 weeks of training
Time frame: 6 weeks
Change from baseline in dual task effect (DTE) for writing amplitude after 12 weeks, including 6 weeks without training
Time frame: 12 weeks
Change from baseline in writing fluency (normalized jerk) on tablet after 6 weeks of training
Time frame: 6 weeks
Change from baseline in writing fluency (normalized jerk) on tablet after 12 weeks, including 6 weeks without training
Time frame: 12 weeks
Systematic Screening of handwriting difficulties (writing on paper) - change from baseline in quality score after 6 weeks of training
Time frame: 6 weeks
Systematic Screening of handwriting difficulties (writing on paper) - change from baseline in quality score after 12 weeks, including 6 weeks without training
Time frame: 12 weeks
Systematic Screening of handwriting difficulties (writing on paper) - change from baseline in writing speed after 6 weeks of training
Time frame: 6 weeks
Systematic Screening of handwriting difficulties (writing on paper) - change from baseline in writing speed after 12 weeks, including 6 weeks without training
Time frame: 12 weeks
Change from baseline in Purdue Pegboard test after 6 weeks of training
Time frame: 6 weeks
Change from baseline in Purdue Pegboard test after 12 weeks, including 6 weeks without training
Time frame: 12 weeks
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 28 Jan 2016.
- Background: PubMed 24447597Broeder S, Nackaerts E, Nieuwboer A, Smits-Engelsman BC, Swinnen SP, Heremans E. The effects of dual tasking on handwriting in patients with Parkinson's disease. Neuroscience. 2014 Mar 28;263:193-202. doi: 10.1016/j.neuroscience.2014.01.019. Epub 2014 Jan 19.
- Background: PubMed 23333265Nackaerts E, Vervoort G, Heremans E, Smits-Engelsman BC, Swinnen SP, Nieuwboer A. Relearning of writing skills in Parkinson's disease: a literature review on influential factors and optimal strategies. Neurosci Biobehav Rev. 2013 Mar;37(3):349-57. doi: 10.1016/j.neubiorev.2013.01.015. Epub 2013 Jan 16.
- Neuromotor Rehabilitation Research Group KU LeuvenLink provided by the sponsor.
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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.
Alice Nieuwboer, Professor principal investigator
KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Writing program and Stretch & Relaxation program in people with Parkinson Disease, run by KU Leuven at 1 site in Belgium.
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 3 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 28 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 from baseline in writing amplitude (cm) on tablet after 6 weeks of training (time frame: 6 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02288052, which also lists 2 linked publications.
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 28 Jan 2016.