The primary objective of the proposed research is to investigate in patients with PDD the efficacy of STN-DBS with best oral medical treatment (DBS-group) for disabling motor symptoms during off-drug phase compared to best oral medical treatment…
ID
Source
Brief title
Condition
- Nervous system, skull and spine therapeutic procedures
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
- Surigical procedure
N.a.
Outcome measures
Primary outcome
<p>Patients will be assessed at baseline, 15 weeks, 30 weeks and 52 weeks after<br />
randomization. The primary outcome measure is the change from baseline to 30<br />
weeks follow-up of motor symptoms in off-drug phase measured with the Movement<br />
Disorder Society - Unified Parkinson*s Disease Rating Scale (MDS-UPDRS) part<br />
III.</p>
Secondary outcome
<p>The secondary outcome measures include neuropsychological evaluation,<br />
psychiatric assessment, additional motor evaluations during on-drug phase,<br />
functional health status, falls, usage of medication, (S)AEs, treatment<br />
satisfaction, caregiver burden, medical care consumption and recruitment and<br />
retention rate.<br />
<br />
The outcome measures of the exploratory part of the study include low-fidelity<br />
LFP data, high-fidelity LFP data, triggered LFP recordings, and paper patient<br />
diaries.</p>
Background summary
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established
treatment for disabling motor symptoms of Parkinson*s disease (PD) that persist
despite optimal pharmacological treatment. Currently, apparent cognitive
impairment (e.g., dementia) is considered a contra-indication for DBS. However,
the scientific underpinning to withhold these patients DBS is weak. In
addition, DBS-surgical procedures have developed considerably in recent years.
If the proposed research demonstrates that DBS is efficacious in patients with
PD and dementia (PDD), a large group of patients may benefit from the treatment.
The explorative part of the study will investigate the correlation between
cognitive and neuropsychiatric symptoms and neuronal activity in PDD. The
objectives hereof are to determine if specific local field potential (LFP)
patterns in the STN are linked to cognitive fluctuations and neuropsychiatric
symptoms (such as psychotic symptoms and anxiety) in patients with PDD.
Study objective
The primary objective of the proposed research is to investigate in patients
with PDD the efficacy of STN-DBS with best oral medical treatment (DBS-group)
for disabling motor symptoms during off-drug phase compared to best oral
medical treatment alone (BMT-group). The secondary objective is to compare
development of cognitive and psychiatric problems, on-drug phase motor
symptoms, functional health status, falls, usage of medication, (serious)
adverse events ((S)AEs), treatment satisfaction, medical care consumption and
caregiver burden between the DBS-group and BMT-group in addition to determining
the recruitment and retention rate.
Study design
The study is a single center prospective, randomized, open-label, blinded
end-point clinical trial (PROBE design).
Intervention
During the DBS surgery high frequency stimulation electrodes will be placed
bilaterally in the STN. Next a pulse generator will be implanted subcutaneously
under the clavicula, which can adjust current, pulse width and frequency. All
patients will receive BMT, consisting of PD-treatment according to current
guidelines and can be adjusted accordingly.
Study burden and risks
Currently, dementia is considered a contra-indication for DBS in PD, because a
thought of concern is that patients with dementia have a greater risk of
cognitive deterioration and complications such as delirium and psychosis.
However, there is no evidence suggesting that this risk is much higher for
patients with dementia compared to patients without dementia. DBS appears to be
safe in case series including patients with PDD as well as in clinical studies
with patients undergoing experimental DBS for dementia. An important possible
benefit is the improvement in motor symptoms.
It is hypothesized that the risks for (S)AEs is acceptable for patients with
PDD undergoing DBS, however, the study could show that this is actually not the
case. The operation will take place under general anesthesia instead of local
anesthesia. The surplus in burden related to treatment for patients randomized
to DBS-group consists of the screening of motor symptoms during on-drug and
off-drug phase with the MDS-UPDRS 30 weeks after randomization (a two-days
hospital stay), and four days of hospitalization for the DBS surgery. The
surplus in burden for evaluating the outcome measures and travel time accounts
for approximately 5 to 8 hours. Patients allocated to BMT-group experience no
additional burden related to treatment, as they will receive care in line with
standard practice. The burden associated with the extra assessments is
approximately 6 to 9 hours.
If patients randomized to DBS agree to collect additional observational data
for the explorative part investigating the correlation between cognitive and
neuropsychiatric symptoms and neuronal activity in PDD, one additional hospital
visit of 15 minutes and an at-home observation period of seven days will be
added to the burden. The in-hospital visit encompasses extensive LFP recordings
while sitting still and performing cognitive tasks. During the at-home
observations, participants and caregiver will be instructed to trigger a
broad-band (0-125 Hz) LFP recording (i.e., an *event*) via their patient
programmer upon the occurrence of psychotic symptoms (hallucinations), anxiety
symptoms (nervousness, restless or tense), at a moment of bad cognition, and at
a moment of relatively good cognition. Additionally, participants and
caregivers will fill out paper patient diaries on the aforementioned symptoms.
V Sisodia
Meibergdreef 9
Amsterdam 1105AZ
Netherlands
020-5662500
r.m.debie@amsterdamumc.nl
V Sisodia
Meibergdreef 9
Amsterdam 1105AZ
Netherlands
020-5662500
r.m.debie@amsterdamumc.nl
Trial sites in the Netherlands
Listed location countries
Age
Inclusion criteria
- age 18 years and older;
- diagnosis of PD according to the clinical diagnostic criteria of the Movement Disorder Society (MDS);
- despite optimal pharmacological treatment, at least one of the following symptoms, that are severe enough to impair functioning in daily life independent of dementia:
- motor response fluctuations;
- dyskinesia;
- painful dystonia;
- levodopa-responsive bradykinesia;
- diagnosis of probable or possible PDD based on the MDS clinical diagnostic criteria (amongst others this encompasses the development of dementia áfter established diagnosis of PD). This will be based on a standardized neuropsychological examination:
- 1 impaired cognitive domain consisting of 2 abnormal tests (i.e., ≤ 2 standard deviations);
- 1 impaired cognitive domain consisting of 2 MCI tests (i.e., ≤ 1.5 standard deviations);
-
Cognitive deficits severe enough to impair daily life (social, occupational, or personal care), independent of the impairment ascribable to motor of autonomic symptoms.
If a test cannot be executed due to severe cognitive difficulties the test is regarded to be abnormal. In case of doubt regarding the presence of PDD, the case will be discussed in a multidisciplinary meeting with neurologists and neuropsychologists;
- a life expectancy of at least two years;
- subject has decision capacity to give informed consent, judgement of which is at the discretion of an experienced neurologist from the study team (see 7.3);
- subject provides written informed consent;
- regular contact with a caregiver, who has at least approximately twice a week contact with the subject and also provides written informed consent for their own participation.
Exclusion criteria
• any neurodegenerative disorder other than PD;
• previous neurosurgery for PD (e.g., DBS, pallidotomy, thalamotomy). Nota
bene: intrajejunal levodopa infusion or subcutaneous apomorphine infusion are
not considered an exclusion criterion;
• contraindications for DBS-surgery, such as a physical disorder making surgery
hazardous;
• Hoehn and Yahr stage 4 or 5 at the best moment during the day;
• co*existence of another abnormality or disorder:
o that causes cognitive impairment that may improve with specific treatment; OR
o that besides PDD is judged to contribute significantly to the cognitive
impairment by the treating physician;
• current major depressive episode according to the fifth edition of the
Diagnostic and Statistical Manual of Mental Disorders (DSM-5);
• current psychosis (treatment with antipsychotics is allowed);
• other severely disabling condition;
• immobility during the greater part of the day not related to off-drug phase
(e.g., due to apathy);
• pregnancy, breastfeeding, and women of childbearing age not using a reliable
method of contraception.
Design
Recruitment
Medical products/devices used
IPD sharing statement
Plan description
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
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 |
|---|---|
| OMON | NL-OMON54196 |
| CCMO | NL76772.018.21 |
| CCMO | NL76772.018.21 |
| Research portal | NL-007778 |