The primary objective is to investigate the cognitive effect of low-frequency stimulation of the nucleus basalis of Meynert (NBM) in advanced Parkinson*s disease (PD) patients, who were previously treated with deep brain stimulation (DBS) of the…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary measure of this study is the cognitive performance of the
subjects, assessed by the symbol digit modality test (SDMT), the Vienna test
system (VTS) - Attention, and the verbal fluency test.
Secondary outcome
(1) The measure of resting cortical activity performed by
electroencephalography (EEG) at baseline and weekly at the end of each period
of crossover trial
(2) Assessment of motor function. The Unified Parkinson*s Disease Rating Scale
(UPDRS) part III (motor examination) and part IV (motor complication) will be
performed at the beginning of the screening trial before adjusting the DBS
setting, and at the end of the three-day screening trial of the NBM-DBS.
(3) Safety and tolerability of the low-frequency stimulation of the NBM in this
study is defined as any adverse effects associated with the adjustment of the
DBS setting during the screening phase as well as in the crossover phase.
Background summary
Cognitive impairment leading to dementia is prevalent in Parkinson*s disease
(PD), and mainly exhibits deficits in attention, memory, visuospatial function
and executive function. It is pathologically characterized by a profound
degeneration of cortically projecting cholinergic neurons of the basal
forebrain, mainly in the region named the nucleus basalis of Meynert (NBM).
Low-frequency deep brain stimulation (DBS) of the NBM has emerged as an
alternative therapy for Parkinson*s disease dementia since acetylcholinesterase
inhibitor, as current pharmacotherapy, cannot halt disease progression, and
therefore, causing suboptimal efficacy. The technique to implant DBS
quadripolar electrodes, targeting to the globus pallidus interna (GPi) for PD
motor symptom treatment, gives a high possibility of placing the most distal
electrode at the NBM. Therefore, stimulation of the NBM in these patients is
feasible by switching the stimulation program which is initially targeting to
the GPi. It is hypothesized that low-frequency stimulation of the NBM will
increase cholinergic neurotransmission from the NBM to its cortical projection
and thereby improving patients* cognition.
Study objective
The primary objective is to investigate the cognitive effect of low-frequency
stimulation of the nucleus basalis of Meynert (NBM) in advanced Parkinson*s
disease (PD) patients, who were previously treated with deep brain stimulation
(DBS) of the globus pallidus interna (GPi). The secondary objectives are to
investigate the effect of low frequency stimulation of the NBM on cortical
activity; to investigate the safety and tolerability of low frequency
stimulation of the NBM in patients who were previously treated with GPi-DBS; to
investigate the effect of temporarily switching off DBS of GPi on motor
function.
Study design
this is a pilot study to perform DBS of the NBM, which consists of two phases:
three days of a screening trial followed by two weeks of a randomized,
single-blind, crossover trial.
Intervention
Using an external programming device provided by Medtronic, the existing DBS
program which initially aims to stimulate the GPi will be temporarily
reconfigured to stimulate the NBM. In the screening phase, the pulse width and
the frequency of the stimulation parameters will be locked at 90 µsec and 20
Hz, while while the voltage will be set according to the predictive value of
the minimal voltage which is able to reach the NBM, up to 4 Volt, or the
highest voltage that is well-tolerated by the subject. These parameters are
further used in the crossover phase.
Study burden and risks
The first phase of the study requires subjects to be hospitalized for three
days in order to evaluate the safety and tolerability of the NBM DBS as well as
to determine an optimal voltage of NBM stimulation to be used in the crossover
trial. The former DBS setting, aiming to stimulate the GPi at high frequency,
will be altered temporarily to stimulate the NBM at low frequency. Evaluations
on subjects* motor and cognitive function, taking about 60 minutes, will be
performed at the beginning and at the end of the screening phase. During this
phase, the dose of dopaminergic medications will be adjusted and if necessary
subcutaneous apomorphine will be used, to compensate the change of DBS setting.
Only if there is no significant deterioration of motor function (an increase of
UPDRS part III more than 30%), subjects are eligible to continue to the second
phase of the study which is the crossover trial phase. Subjects will undergo a
week of stimulation of the NBM and another week without DBS stimulation. Three
visits are planned during this two-week study. EEG and NPE will be performed at
each visit, which takes about 1.5 hours. With regard to the safety of
stimulating the NBM, based on previous studies (Freund et al., 2009; Kuhn et
al., 2009), low-frequency stimulation of the NBM was well tolerated and several
improvements of cognitive performance were shown. No further adverse event was
found except one complaint about inner restlessness due to stimulation
intensity more than 5V. Of note, the NBM will be stimulated by the most distal
electrode of the same lead used for GPi-DBS. No additional surgery or any other
invasive intervention will be performed.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
1. Patient with GPi stimulation, with the NBM in reach of the electric field at least one DBS electrode
2. Patients should be able to give informed consent
3. patients should be on a stable medication regimen for at least 4 weeks
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study if any unstable internal disease is found.
Additional exclusion criteria is made to determine whether or not a subject can continue to the crossover trial. Subject with significant worsening of motor function during the screening trial, which is indicated by an increase of the UPDRS part III score more than 30%, will not continue to the crossover trial.
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
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02763397 |
| CCMO | NL57011.042.16 |