The objective of this pilotstudy is primarily to assess a cost-efficient, easy accessible training of cognitive functions on its feasibility and initial effect in patients with cognitive dysfunction in PD, MS of patients treated with ECT. Using this…
ID
Source
Brief title
Condition
- Other condition
- Movement disorders (incl parkinsonism)
- Cognitive and attention disorders and disturbances
Synonym
Health condition
MS, depressieve ouderen behandeld met ECT
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary studyparameters aim to measure the feasibility of the intervention
and challenge the patients experience while using the intervention. This will
be measured by a questionnaire consisting of four-point Likert scales, which
assess the patients' opinion of the intervention on several aspects.
Secondary outcome
The secondary study parameters are first off the training effect of the
intervention, which will be measured by the interaction effect between time of
measurement (T0 versus T1, of T0 versus T2) and condition (experimental versus
control). If possible, parallel tests will be used to correct for repeated
neuropsychological testing. The objectively measured training effect will be
assessed on the most affected cognitive domain, different per syndrome:
- PD: change in executive functions, measured by change in the Trail Making
Task, Stroop Color Word Test and Letter Fluency.
- MS: change in episodic memory, measured by change in the Rey Auditory Verbal
Learning Test and/or the Location Learning Test.
- postECT: change in executive function, as measured by change in the Trail
Making Task, Stroop Color Word Test and Letter Fluency.
Second, the secondary studyparameters are change in subjective cognitive
complaints as reported by the patient, measured by the Cognitive Failure
Questionnaire (CFQ).
Background summary
In neurodegenerative disorders and psychiatric disorders, cognitive dysfunction
is frequently reported. In Parkinson's disease (PD), Multiple Sclerosis (MS)
and patients treated with electroconvulsive therapy after a severe or therapy
resistant depression (postECT), executive dysfunction are prevalent (Bosboom,
Stoffers & Wolters, 2004; Chiaravalloti & DeLuca, 2008; Rubin, Kinscherf,
Figiel & Zorumski, 1993). However, cognitive dysfunction is heterogeneous,
within these groups as well as between, and it is not limited to one cognitive
domain. In PD and MS, problems in attention and episodic memory are also
frequently described (Bosboom et al. , 2004; Chiaravalloti & DeLuca 2008; Rao,
Leo, Bernardin & Unverzagt, 1991). These dysfunctions can appear already early
in the disease (Achiron & Barak 2003; Muslimovi*, Post, Speelman & Schmand,
2005). The majority of PD patients - estimations are about 80% - develops PD
dementia (Aarsland, Andersen, Larsen, Lolk & Kragh-Sørensen, 2003; Hely, Reid,
Adena, Halliday & Morris, 2008). In MS, about half of the patients experiences
problems in cognitive functions (Rao et al., 1991). ECT can recover patients
with severe and/or therapy resistant depression. However, 30-50% of these
patients develops severe cognitive dysfunction in the executive dysfunction as
well as in attention and autobiographical memory (Rubin et al., 1993; Oudega et
al. 2014). Recovery appears often within six months after ECT. However,
performances remain below-average compared to normgroups and there are large
individual differences (Verwijk et al., in prep.). The cognitive difficulties
in MS and PD have a significant negative influence on the quality of life
(Chiaravalloti & DeLuca 2008; Klepac, Trkulja, Relja & Babi*, 2008). Cognitive
dysfunction in PD is associated with decreased independent daily functioning,
hospitalization and the development and severity of neuropsychiatric symptoms
(Fletcher, Leake, Marion, 2011). Furthermore, in the clinic cognitive
dysfunction has been reported to be one of the most dreadful side effects of
ECT. However, effective treatment of the described cognitive dysfunction is
still in its infancy, possibly due to heterogeneity in cognitive problems and
the pathological mechanisms that underly these (Hoffmann, Tittgemeyer & Von
Cramon, 2007; Guimarães & Sà, 2012; Gerrits et al., 2014; Robbins & Cools,
2014; Verwijk et al., in prep.). For example, pharmacological interventions
using levodopa or cholinesteras-inhibitors are very limitedly effective
(Svenningson, Westman, Ballard & Aarsland, 2012).
Cognitive training is based upon the principle that plasticity of the brain can
facilitate function improvement by intensive training. In Alzheimer's disease,
cognitive training has shown significant improvemend in cognitive functions
(Olazaran et al., 2010) and in traumatic brain injury cognitive training is
advised to treat cognitive dysfunction (Cicerone et al., 2011). Moreover,
complex cognitive training has shown positive effects on cerebral bloodflow and
functional and structural connectivity in healthy elderly (Chapman et al.,
2015). A meta-analysis in Alzheimer's disease showed that restorative training
methods (i.e. training specific functions) had larger effect sizes as compared
to compensatory training methods (e.g. strategy training) (Sitzer, Twamley &
Jeste, 2006). Furthermore, computerized training methods have shown larger, or
at least comparable effect sizes as compared to traditional pen-and-paper
methods in healthy elderly (Kueider, Parisi, Gross & Rebok, 2012). In MS and
PD, there have been earlier studies in the effect of cognitive training on
functioning. In MS, a memory training was shown to be specifically effective in
patients with moderate cognitive dysfunctions (Chiaravalloti, DeLuca, Moore &
Ricker 2005). In PD, a systematic review showed that various cognitive training
methods (e.g. pen-and-paper, simple sudoku, computer training) had small to
large effects on cognitive functioning (Hindle, Petrelli, Clare & Kalbe, 2013).
However, earlier studies have been small, frequently without a controlled
design (Hindle et al., 2013; Rösti-Otajärvi & Hämäläinen, 2011). Additionally,
earlier cognitive training programs have frequently been executed in a health
care organization, impairing patients to successfully attend all training
sessions due to mobility impairments. Also, there are limited studies in the
effects of cognitive training on improved functioning of daily living and
neuropsychiatric symptoms like anxiety and depression. Given the fact that
there is an absence in cognitive training studies in patients post-ECT, there
is no knowledge about the ability of cognitive training to speed up the natural
course.
Using this pilotstudy, we aim to study the feasibility of a randomized
controlled trial using an online computerized intervention for training
cognitive abilities in three patient groups. By using a double-blinded,
controlled study design, we keep in mind limitations of earlier comparable
studies. If this treatment proves to be feasible, and a rough estimated effect
sized are positive, a larger randomized controlled trial can be executed to
study the effectivity of this treatment. When effects are positive, an online
cognitive training programme could prove to be a cost-efficient intervention
that is accessible at home - something which is important for patients impaired
in mobility.
Study objective
The objective of this pilotstudy is primarily to assess a cost-efficient, easy
accessible training of cognitive functions on its feasibility and initial
effect in patients with cognitive dysfunction in PD, MS of patients treated
with ECT. Using this pilotstudy, we aim to assess if a larger randomized
controlled trial is feasible.
Primary objective: is BrainGymmer feasible and challenging in the previously
mentioned syndromes?
Secondary objective: what is (an estimation of) the effect of BrainGymmer on
the subjective cognitive functioning of the patient (as measured by both the
patient and the caregiver) and the objective cognitive functioning of the
patient (as measured by an extensive neuropsychological assessment) in PD, MS
and patients treated with ECT?
Study design
This pilotstudy uses a double-blinded, randomized controlled design. N = 10 for
each syndrome, and both intervention groups - total N = 60. Patients will be
randomly and double-blind assigned to either the training intervention or the
control condition. Both conditions will perform the training/activities 45-60
minutes a day, three times a week during eight weeks. Before the start, at the
end of intervention and a month after the end of intervention, a
neuropsychological assessment and questionnaires will be taken. After the end
of the intervention, participants will be asked to review the intervention by
filling in a questionnaire that uses four-point Likert scales.
Intervention
The intervention aims to train several cognitive abilities; especially the
executive functions, attention, working memory and processing speed. The
control condition consists of cognitive activities that do not intend to train
cognitive functions, such as simple puzzles, domino and solitaire. An online
training program, BrainGymmer (www.braingymmer.nl), is used to have patients
perform the training sessions independently at home. The choice for this
intervention is based on the fact that it is an online training method with
challenging and (on the first sight) valid games, which is used in other
(running) studies at the UvA and Leiden University (e.g. TAPASS -
www.tapass.nl). The mental processes that are appealed to by the intervention
are similar to processes that are trained in classic face-to-face training
methods. Both the intervention protocol and the control condition will contain
several games that have the participant train cognitive functions/perform
cognitive activities for 45-60 minutes each session. The games are equipped
with a so-called 'dynamic difficulty adjustment', which means that the
difficulty is adaptive to the participants' performance. Using this adjustment,
the games adapt to the (baseline) cognitive abilities of each participants, and
it challenges them to improve on each task. Furthermore, BrainGymmer is an
interactive platform, wherein performances can be measured and compared to
other participants in the study. During the intervention, the participants will
be contacted every other week to evaluate the progression, to motivate them and
to answer possible questions. Moreover, the patients' compliance will be
recorded by BrainGymmer and will be sent every week to the researcher. The
training games will be presented sequentially, until every game in the training
protocol has been performed. In the PD-group, patients will be asked to perform
the training/tasks an hour after taking their dopaminergic medication, to
control for ON/OFF fluctuations. In this manner, patients will be trained in
the ON-phase, to minimalize the effect of motor symptoms on performing the
intervention.
Study burden and risks
In this study, the participant will be asked three times to visit the VUmc. At
each visit, a neuropsychological assessment (± 60 minutes) and questionnaires
(± 20 minutes) will be assessed. During the intervention patients will carry
out an online training program or 'control' cognitive activities for 45-60
minutes, three times a week during eight weeks. The risk associated with this
intervention is negligible, while the chances of improved cognitive functions
are realistic on the basis of earlier research. The intervention is not
specifically designed for one disease type; the intervention will be assessed
in multiple disease wherein cognitive disorders are similar.
van der Boechorststraat 7
Amsterdam 1018BT
NL
van der Boechorststraat 7
Amsterdam 1018BT
NL
Listed location countries
Age
Inclusion criteria
General criteria:
- Patients have (access to) a computer with access to the Internet. Patients are capable of using a keyboard and computer mouse.
- Patients are willing to sign informed consent.
PD-specific criteria:
- Cognitive dysfunction is apparent on at least one out of three executive function tests (i.e. Stroop, Trail Making Task, Fluency), which is defined as follows: 30 <= T-score <= 43. T-scores are based on Dutch norm groups (e.g. Schmand, Houx & De Koning, 2012) that are distributed normally with M = 50 and SD = 10. In Dutch neuropsychology, these scores are used to correct testscores for age, sex and education effects.
- Patients are diagnosed with Parkinson's disease according to the United Kingdom Parkinson*s Disease Society Brain Bank criteria (Hughes, Daniel, Kilford & Lees, 1992).
- Patients are in Hoehn & Yahr stadium < 4, and are medically stable during a month prior to the intervention. The medication will be attempted to remain stable for the remainder of the intervention.
- Patients are 50 to 70 years old.
MS-specific criteria:
- At least one episodic memory task (i.e. Rey Auditory Verbal Learning Test, Location Learning Test) shows deficit, which lies at least 1 SD below the mean of healthy normpopulation (Schmand, Houx & De Koning, 2012).
- Patients have been diagnosed with MS for a period longer than three month prior to inclusion in this study according to the renewed McDonald criteria (Polman et al., 2011).
- Patients have been on stable medication for at least three months.
- Patients are 20 to 60 years old.
postECT-specific criteria:
- Unipolar depressive patients indicated for ECT, who experience cognitive complaints after treatment with ECT.
- Patients have undergone the full ECT-procedure.
- Phonemic fluency and/or autobiographical memory (measured by the Kopelman Autobiographical Interview) show deficit: significant individual detoriation is present (> 1.0 SD detoriation), accounting for test- retesteffects.
- Patients are 18 to 100 years old.
Exclusion criteria
General criteria:
- Indications for presence of dementia.
- Presence of traumatic brain injury.
- A psychiatric disorder (in the postECT group: other than unipolar depression).
- No history or presence of drug or alcohol abuse.
- Inability to undergo a neuropsychological assessment (e.g. due to fast fatigue, seeing problems or language barrier).
PD-specific criteria:
- Psychotic symptoms, as screened by the Questionnaire for Psychotic Experiences (QPE). Benign hallucinations with insight are not contraindicated).
MS-specific criteria:
- Patients with MS can't have relapses or can't use corticosteroids 4 weeks prior to the start of the study.
postECT-specific criteria:
- Indications for presence of delirium.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02525367 |
| CCMO | NL54022.029.15 |