The primary objective of this study is to assess the acceptability and feasibility of four-week, high-frequency rTMS and anodal high-definition tDCS of the DLPFC as potential intervention methods for the treatment of PD-MCI. Secondary study…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Acceptability of the interventions, as measured with an acceptability
questionnaire based on the Theoretical Framework of Acceptability (*TFA-PD
questionnaire*; Sekhon et al., 2017, 2022).
Secondary outcome
1) Acceptability and feasibility outcomes supporting the main study parameter,
including a) objective feasibility data on intervention compliance and
attrition indices of drop-out, b) feasibility of at-home tDCS usage measured
with the System Usability Scale (Brooke, 1996), and c) acceptability of the
interventions based on qualitative data from focus groups, co-led by the
involved end users (*patiëntonderzoekers*) from the Dutch PD Patient
Association;
2) Subjective cognitive function (PD-Cognitive Functional Rating Scale;
Cognitive Failures Questionnaire);
3) Objective cognitive function (Trail Making Test, Letter Fluency, Tower of
London, Rey Auditory Verbal Learning Test (*15 Woordentest*), Symbol Digit
Modalities Test, Wechsler Adult Intelligence Scale IV-NL - Digit Span subtest);
4) Neuropsychiatric symptom severity (depression: Beck Depression Inventory-Ib;
anxiety: Parkinson Anxiety Scale);
5) Functional mobility (Timed Get-up and Go test);
6) Structural and functional neuroimaging to enhance precision of DLPFC
targeting.
Background summary
Mild cognitive impairment (MCI) is a highly prevalent non-motor characteristic
in Parkinson*s disease (PD) affecting about 40% of individuals (Baiano et al.,
2020). PD-MCI is associated with limitations in daily life functioning and
quality of life, and with neuropsychiatric symptoms. Importantly, it
constitutes a risk factor for later development of PD-related dementia
(Hoogland et al., 2017).
There are no curative treatment options for PD*or PD-MCI*yet. Symptomatic
treatment of cognitive impairment in PD currently consists of optimization of
dopaminergic therapy, improving cognitive inflexibility and bradyphrenia, but
also exacerbating other cognitive deficits (Robbins & Cools, 2014). Despite
many endeavors to pharmacologically improve PD-MCI, there is no effective
medicament. Additionally, other, non-pharmacological treatment options such as
cognitive training have shown moderate effect sizes, but with limited transfer
to daily functioning (Gavelin et al., 2022; Orgeta et al., 2020).
Non-invasive brain stimulation (NIBS) through repetitive transcranial magnetic
stimulation (rTMS) or transcranial direct current stimulation (tDCS) may show
promise in treating PD-MCI (Dinkelbach et al., 2017; He et al., 2022; Jiang et
al., 2020; Suarez-Garcia et al., 2020). NIBS is, however, intensive and complex
in use, specifically for individuals with motor and cognitive difficulties,
which might limit its potential for clinical use.
Study objective
The primary objective of this study is to assess the acceptability and
feasibility of four-week, high-frequency rTMS and anodal high-definition tDCS
of the DLPFC as potential intervention methods for the treatment of PD-MCI.
Secondary study objectives include:
1) Explore demographic and clinical factors that impact the acceptability and
feasibility of NIBS for the treatment of PD-MCI.
2) Render separate effect size estimations for the efficacy of rTMS and tDCS on
cognitive function, measured with subjective cognitive function questionnaires
and objective measurements (neuropsychological assessment).
3) Explore the effects of NIBS on neuropsychiatric symptoms and functional
mobility.
4) Explore the use of functional and structural MRI to optimize
neurostimulation targeting in PD-MCI.
Study design
This intervention study will adapt a cross-over design with three conditions: a
baseline condition, rTMS, and tDCS.
Intervention
Participants will undergo four consecutive phases: 1) a no-intervention
baseline condition, 2) 12 sessions of 20-minute repetitive transcranial
magnetic stimulation (rTMS) (10Hz) or anodal transcranial direct current
stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC),
3) a second no-intervention baseline condition, 4) the second NIBS
intervention. All phases have a duration of 4 weeks and the NIBS interventions
are counterbalanced between two groups.
Study burden and risks
The study consists of 1) two four-week intervention periods, with three
(rTMS)/five (tDCS) 20-minute intervention sessions per week. For the rTMS
intervention, stimulation will be performed at the Amsterdam UMC, location VUmc
(and thus includes travel time); 2) one 120-minute assessment (baseline) that
includes neuropsychological and motor assessment, and MR imaging, and four
60-minute assessments that only includes neuropsychological and motor
assessment.
The risks of the intervention have been shown to be small for individuals with
Parkinson*s disease, are minimized by the exclusion criteria and the
intervention protocols fall within the reported safety guidelines. The research
team is experienced in the use of both interventions in a variety of
populations (e.g., stroke, obsessive-compulsive disorder, elderly with bipolar
disorder). Moreover, the research team is experienced in the execution of
clinical trials on non-pharmacological interventions for the treatment of
non-motor symptoms in Parkinson*s disease (e.g., bright light therapy,
cognitive training, acceptance & commitment therapy). There are no risks of the
assessments.
There is a potential benefit of NIBS on cognitive function, based on small
earlier studies. Additionally, NIBS targeted at the DLPFC may positively
impact depressive symptoms.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
- Clinical diagnosis of Parkinson*s disease, diagnosed by a neurologist;
- Mild to moderate disease stage (Hoehn & Yahr disease stage < 4);
- Movement Disorders Society Level I criteria for PD-MCI;
- In case of (dopaminergic) medication use, participants are on stable
medication for at least one month before participation and expect to remain on
stable medication during the study.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Indication for dementia based on the SAGE (cut-off < 14; Scharre et al.,
2010);
- Severe depressive disorder (Beck Depression Inventory - Ib score > 18);
- Psychotic disorder (except for benign hallucinations with insight), screened
with the Scale for Assessment of Positive Symptoms for Parkinson*s disease;
- Indication of alcohol or drug abuse;
- Contra-indication for NIBSrTMS according to Magstim Rapid2 Manual; rTMS
should not be::
• used on or in the vicinity of patients or users with cardiac demand
pacemakers, implanted medication pumps, cochlear devices, implanted
defibrillators and/or implanted neurostimulators
• used on or in the vicinity of patients with implanted metal objects• used on
patients where the skin in the area to be contacted is broken
• used on patients who suffer from multiple sclerosis
• used on those with large ischaemic scars
• used on pregnant women
• used on infants under the age of 2 years
• used on epileptic individuals
• used on those with a family history of convulsions
• used on individuals with brain lesions that could affect seizure threshold
• used on individuals suffering from multiple sclerosis
• used on individuals taking tricyclic antidepressants, neuroleptic agents or
any other drug that could lower seizure threshold,
• used on individuals suffering from sleep deprivation during rTMS procedures
• used on individuals with a heavy consumption of alcohol or those using
epileptogenic drugs
• used on individuals with severe heart disease or with increased intracranial
pressure be used on those who have uncontrolled migraines
- Contra-indication for tDCS according to Neuroelectrics Starstim Manual; tDCS
should not be used in case of:
• Patients with a history of seizures;
• Patients with unexplained episodes of loss of consciousness, since such
condition could be related with brain alterations or epilepsy;
• Patients with unstable or non-controlled neuropsychiatric illness;
• Patients having implanted brain medical devices;
• Patients with implanted pacemakers;
• Patients having any electrically, magnetically or mechanically activated
implant;
• Patients having cardiac, neural or medication implants;
• Patients having vascular clips or any other electrically sensitive support
system in the brain;
• Patients with serious brain injury;
• Patients showing damage of skin at sites of stimulation (the device can only
be used in healthy skin without wounds, otherwise the resistance to current can
be altered);
• Patients suffering from skin problems, such as dermatitis, psoriasis or
eczema;
• Patients suffering from severe or frequent headaches;
• Patients with any serious life-threatening disease such as congestive heart
failure, pulmonary obstructive chronic disease or active neoplasia;
• Pregnant women (women of childbearing age should undertake a pregnancy test
to confirm eligibility before treatment).
- Contra-indication for MR imaging:
• metal in the body (pacemaker, port-a-cath, prosthesis, (cochlear) implant) •
previous brain surgery
• head trauma that resulted in unconsciousness for at least 1 hour • clips
• (old metal containing) tattoo • irremovable piercings
• irremovable metal braces • pregnancy
• claustrophobia other problems lying still for 45 minutes • metal in the teeth
• neurostimulator (including deep brain stimulation)
- Space-occupying lesion on MRI.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| CCMO | NL84843.018.23 |