To investigate whether impairments of shifting between response sets underlie motor freezing in PD and to investigate the efficacy and the neural mechanism by which MPH improves gait and cognition in PD patients with FOG.
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
- Cognitive and attention disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
First primary outcome: performance of PD patients with FOG on behavioral tasks
compared to PD patients without FOG and healthy controls.
Second primary outcome: cerebral activation patterns during shifting between
response sets in PD patients with FOG, relative to PD patients without FOG and
healthy controls.
Third primary outcome: change of performance on response shifting task and gait
trajectory after administration of MPH in PD patients with FOG, relative to
placebo.
Fourth primary outcome: cerebral activation change after administration of MPH
in PD patients with FOG, relative to placebo.
Secondary outcome
First secondary outcome is the performance on the motor tasks of all groups,
compared to the performance on the cognitive task and dual task.
Second secondary outcome is the cerebral activation patterns during shifting
between motor tasks in all groups compared to the cerebral activation patterns
during shifting between cognitive tasks and during dual tasks.
Background summary
Freezing of gait (FOG) is common in Parkinson*s disease (PD). The underlying
mechanism of FOG is however unknown. It was hypothesized that PD patients with
FOG are unable to keep different tasks (motor or cognitive) on-line and can not
flexibly shift between response sets. Whether shifting impairments underlie the
mechanism of motor freezing has never been investigated.
Impairments in set-shifting have been associated with a reduced activation in
the fronto-striatal circuits in PD. Thus, if impairments in shifting between
response sets underlie motor freezing there may be a close inter-relationship
between the fronto-striatal circuitry disturbances underlying both shifting
impairments and motor freezing.
Treatment options are insufficient to relieve FOG in PD. Recently,
Methylphenidate (MPH) has been introduced as a treatment option. No randomized,
clinical controlled trial has been performed to investigate the efficacy of MPH
for FOG in PD.
Furthermore, there is no understanding of the neural mechanism by which MPH
ameliorates cognition and gait in PD. Studies suggest that the neural effects
of MPH vary according to task requirements. In healthy controls MPH modulated
the striatal activity when response shifting was required.
Study objective
To investigate whether impairments of shifting between response sets underlie
motor freezing in PD and to investigate the efficacy and the neural mechanism
by which MPH improves gait and cognition in PD patients with FOG.
Study design
This study can be described as a randomized, double-blind, controlled trial,
which will consist of the following parts:
a. Pilot study. This part of the study is focused on the applicability of the
behavioral task and the efficacy of Methylphenidate. The set-shifting may be
adjusted based on the results of the pilot.
b. Selected participants will be invited for two visits to the UMCG. The first
visit will consist of a short neuro(psycho)logical exam and performing the
set-shifting task. In all patients it will in addition be determined whether
they are freezers. PD patients with FOG will also receive a physical exam.
During the second visit all participants will be assessed with the shifting
task during fMRI-EMG.
c. PD patients with FOG will be treated with MPH for three months.
d. After three months the behavioral assessment and fMRI-EMG will be repeated
in PD patients with FOG.
Intervention
Methylphenidate or a placebo shall be administered to all Parkinson's disease
patients with Freezing of Gait.
Study burden and risks
No direct risks are associated with performing the set-shifting task during
fMRI-EMG or outside the scanner. Also the burden of this part of the study is
minimal, since it only requires a certain amount of concentration from which
one normally can recover during a short break.
PD patients with FOG may suffer from adverse events after the administration of
MPH or placebo. In the case of severe or untolerable adverse events the use of
MPH or placebo will be terminated immediately. However, PD patients with FOG
may have a benefit after the administration of MPH, given studies that show a
improvement of gait and cognition in PD from MPH. The risk and burden of this
part of the study may thus be different between patients, depending on the
experienced benefits and adverse events.
Hanzeplein 1
9713 GZ Groningen
NL
Hanzeplein 1
9713 GZ Groningen
NL
Listed location countries
Age
Inclusion criteria
Parkinson's disease according to the criteria of the UK brain bank criteria.
Exclusion criteria
- Presence of neurological central nervous system disorders other that idiopathic PD.
- Surgical treatment for idiopathic PD, such as deep brain stimulation
- Dementia (i.e. a score below the cut-off of the Mattis Dementia Rating Scale)
- Other significant co-morbidity
- Contraindications to MRI scanning (see protocol for a specification)
- Contraindications to the adminstration of Methylphenidate (see protocol for a specification)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-012643-42-NL |
| CCMO | NL28119.042.09 |
| OMON | NL-OMON23006 |