The aim of this study is to assess whether the effectiveness of STN DBS for the treatment of Parkinson motor symptoms using imaging-based DBS programming is non-inferior compared to DBS programming with the current standard practice of clinical…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the mean change from baseline to six months follow-up on
the Movement Disorders Society Unified Parkinson*s Disease Rating scale motor
examination part (MDS-UPDRS III) score in standardized OFF-drug phase.
Secondary outcome
A. Motor symptoms in ON-drug phase (MDS-UPDRS III)
B. Number of hours in OFF-drug phase (MDS-UPDRS IV)
C. Dyskinesia duration and severity (MDS-UPDRS IV)
D. Non-motor symptoms (MDS-UPDRS I)
E. Motor aspects of experiences of daily living (MDS-UPDRS II) for OFF- and
ON-drug phases
F. Level of physical disability, measured with the Academic Medical Center
Linear Disability Score (ALDS)
G. Disease specific quality of life (Parkinson*s Disease Questionnaire 39)
H. Adverse effects
I. Patient satisfaction on the outcome of treatment
J. Patient evaluation of the burden of therapy
K. Proportion of patients for whom it is necessary to switch to the other
intervention arm during the follow-up period
L. Use of care (e.g., number of hospital visits and telephone calls)
M.Total duration of programming sessions
N. Final DBS settings (e.g., electrical current, pulse-width, and frequency)
O. Proportion of patients at six months stimulated at same contact point (for
both hemispheres) suggested by threshold assessment or imaging
P. Local field potentials for patients with PerceptTM PC (Medtronic, Dublin,
Ireland) DBS system (see chapter 5.1 and 6.2)
Exploratory objectives also include the correlation between the assessment of
PD symptoms and neuronal activity at the level of the STN at different time
scales (seconds to minutes). This includes:
A. The correlation of AI-based analysis of bradykinesia (a), tremor (b),
dyskinesia (c) and freezing (d) in weekly home videos with the LFP data.
B. The correlation of AI-based analysis of bradykinesia (a), tremor (b),
dyskinesia (c) and freezing (d) in videos recorded during clinical practice
with the LFP data.
C. The change in LFPs due to DBS or medication.
D. Difference between DBS responders (more than 30% improvement on MDS UPDRS
III score), DBS superresponders (more than 70% improvement on MDS UPDRS III
score), and DBS non-responders.
Background summary
Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is an established
treatment for disabling motor symptoms of Parkinson*s disease (PD). Correct
programming of DBS settings to provide optimal stimulation within the target
region is crucial for a successful clinical outcome. To date, programming of
the DBS settings is done with the threshold assessment. For each contact point
the current is increased in small steps and the severity of motor symptoms and
possible adverse effects are assessed with each step. This process is
challenging and time consuming because of the vast number of possible parameter
combinations. This results in long programming sessions that can be exhausting
for patients and often lead to inconclusive results due to fatigue. Imaging
techniques have been improved greatly over the years and could be useful for
programming DBS based on patient-specific anatomy.
Study objective
The aim of this study is to assess whether the effectiveness of STN DBS for the
treatment of Parkinson motor symptoms using imaging-based DBS programming is
non-inferior compared to DBS programming with the current standard practice of
clinical threshold assessment in DBS of the subthalamic nucleus in patients
with Parkinson's disease.
Study design
The study is a single centre prospective, randomised, open-label, blinded
end-point (PROBE design) clinical trial. Following surgery for DBS
implantation, in total 132 patients will be randomized to DBS programming with
initial imaging-based contact point selection only (Imaging group) or to DBS
programming with initial threshold assessment-based contact point selection
(Threshold group). Follow-up is six months.
Intervention
In both groups (i.e., Imaging and Threshold), DBS programming will start ±4
weeks after DBS surgery. For this programming patients are admitted in the
hospital for a day.
In the Imaging group, the stimulation parameters are determined with help of
the software program Brainlab (München, Germany) with the module GUIDE XT
(Boston Scientific, Marlborough, US). Both programs are CE-marked and
commercially available. The programs are already used in the regular patient
care in the Amsterdam UMC with the preparation of the deep brain stimulatie
surgeries and for the programming of patients where we are unable to find
optimal parameters with the threshold assessment. The recommendation of the
optimal contactpoint(s) and stimulation parameters will be made based on the
localisation of the electrodes towards the patientspecific anatomical
structures. In the program Brainlab the pre-operative MRI-scan and the
post-operative CT-scan will be fused. Based on these images of the patient and
the anatomical atlas of the thalamus and the basal ganlgia as reference, a 3D
reconstructie will be made of the STN and the surrounding structures, with the
DBS-electrodes visible within. In this reconstruction we determine which
contactpoint(s) is located on the most ideal spot (the dorsolateral part of the
STN). With help of the Volume of Tissue Activated (VTA; i.e., the tissue
enclosed within an iso-surface of the activation function), the optimal
parameters will be determined, and will be passed on to the nurse specialist
that will program the DBS-system. The fusion and determination of the
contactpoint(s) and stimulation parameters will be carried out by a research
team member with clinical experience in the use of Brainlab and GUIDE XT.
Programming the DBS-system itself will be performed by the nurse specialist.
The frequency and pulse width will be set to a standard of 130 Hz and µs for
all patients. The optimal amount of electrical current will also be proposed to
the nurse specialist. The start amount of current will be lower than the
proposed amount, given that the Parkinson mediaction will be phased out over
the following months. The exact amount of current will be determined by the
nurse specialist, based on the clinical response of the patient. This method is
already in use in the regular patient care for patients where efficient
stimulation parameters can not be found with the threshold assessment.
In the Threshold group, the preferred stimulation parameters for DBS
programming will be determined according to current clinical practice. During
the threshold assessment, the amount of electrical current needed to generate
symptomatic improvement and the amount of electrical current needed to generate
adverse-effects are determined for every contact point of both DBS leads by
increasing current with 0.5 mA steps from 0 to approximately 5.0 mA. With each
step, severity of Parkinson symptoms and presence of possible adverse-effects
are assessed. For each side (i.e., left and right), the contact point with the
most favourable trade-off between clinical improvement and adverse-effects will
be used for stimulation.
Study burden and risks
The results of the study may well contribute to reducing the burden of DBS
treatment. If imaging-based contact point selection is non-inferior to
threshold assessment-based contact point selection, this may result in more
efficient programming sessions with reduced programming time (less use of
health-care resources) and less discomfort for patients.
The screening at baseline, the threshold-assessment and the assessment at six
months are part of the current standard of care. Participating in this study
does not lead to extra hospital visits; the extra assessments relating to the
trial are scheduled during standard of care appointments or via phone. The
surplus of burden related to assessments for both groups consist of the
randomization, the informed consent conversation (estimated time 30 minutes), a
phone call for follow-up at three months (estimated time 15 minutes) and an
extra questionnaire (estimated time 10 minutes) at six months follow-up.
If the participant chooses participate in the part investigating the
correlation between real time objectified Parkinson*s disease symptoms and
neuronal activity, 2 extra hospital visits will be scheduled. These visits
typically last around 30 minutes and are usually combined with one of the
standard hospital visits related to DBS care. Additionally, the patient is
requested to record a weekly video of their symptoms, taking approximately 5
minutes each time.
The patient has a 50% chance of being randomized to imaging-guided DBS
programming (Imaging group). The expected benefit for this group is that they
will not need the threshold-assessment and therefore have less burden due to
less hospital visits for the programming. There are no extra risks associated
with participation in this study. If the stimulation parameters found with
imaging-guided programming do not yield enough effect in the Imaging group, the
healthcare professionals can choose to execute the threshold-assessment for
these patients.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Parkinson diagnosis based on the clinical diagnostic criteria of Movement
Disorder Society
Referred to Amsterdam UMC for DBS screening
Exclusion criteria
Previous functional stereotactic neurosurgery
Dementia
Current depression or psychosis
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 |
|---|---|
| CCMO | NL84601.018.23 |