Clinical trial NCT04571112: GPi+NBM DBS in Parkinson's Disease With Mild Cognitive Impairment
Official title: Multi-targets, Single-lead GPi+NBM DBS in Parkinson's Disease With Mild Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Memory Disorders
Lead sponsor: University of Toronto
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 6
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: To target both the NBM and GPi in a single trajectory, using the Vercise system (Boston Scientific, Marlborough, Massachusetts, US) which is now approved for human use in Canada. This system includes a novel 8-contact electrode and an IPG system with 16 independent power sources allowing the so-called 'Multiple Independent Current Control' (MICC) that permits concurrent high- and low-frequency stimulation, as well as a variety of amplitudes and pulse widths independently controlled at each stimulated region.
Primary purpose: TREATMENT

Brief summary: This study examines the safety and feasibility of DBS in treating the movement and cognitive dysfunction in Parkinson's disease (PD). Globus pallidus interna (GPi) stimulation is an established treatment for the motor symptoms in PD, but it does not treat the cognitive symptoms that can also be seen in this condition. It is theorized that we can improve cognitive dysfunction by stimulating a part of the brain called the nucleus basalis of Meynert (NBM), which releases a chemical (acetylcholine) and plays a role in memory and attention. By using a novel DBS system (Vercise device) with 2 electrodes that are designed to stimulate the GPi and NBM, we can potentially target the motor and cognitive symptoms of PD with a single intervention.

Detailed description: Neuronal loss within the cholinergic nucleus basalis of Meynert (NBM) correlates with cognitive decline in dementing disorders such as Alzheimer's disease and Parkinson's disease (PD). Deep Brain Stimulation targeting the Globus Pallidus interna (GPi) is an established treatment for the motor symptoms in Parkinson's Disease, and stimulating the NBM is believed to stimulate cognitive function. Targeting these two regions was previously impossible because they require different frequency stimulations, but recent developments in DBS technology allow for the dual stimulation of these nuclei at different frequencies.

This phase-II double-blind cross-over pilot trial will investigate the motor and cognitive effects as well as the presence of adverse effects of combined NBM and GPi DBS. The main goal of this pilot trial is to demonstrate the feasibility and safety of the multi-targeting approach in 6 patients with PDD and disabling motor symptoms.

Eligibility criteria: Inclusion Criteria:

1. PD-MCI that affects multiple cognitive domains (including memory, visuo-spatial deficits etc.). diagnosis based on a comprehensive neuropsychological assessment (gold-standard) allowing the application of Level II MDS diagnostic criteria (Dubois et al. 2007)
2. PD fulfilling standard criteria for bilateral GPi DBS surgery
3. Patient's ability to provide informed consent and comply with study protocol.

Exclusion Criteria:

1. Severe Parkinson's disease dementia, preventing completion of the neuropsychological assessment, compliance with the study protocol, or ability to provide informed consent.
2. Inability to be fluent in English.
3. Unstable dose of any cognitive enhancing medication.
4. Presence of other neurological disorders, severe active psychiatric conditions or previous brain surgery.

Other conditions contraindicating DBS, PET scanning or MRI scanning.

Primary outcomes:
measure: Change in cognition after GPi/NBM DBS
timeFrame: at baseline and 6, 14, 22, 30 and 52 weeks post surgery
measure: Change in motor function (UPDRS)GPi/NBM DBS
timeFrame: at baseline and 6, 14, 22, 30 and 52 weeks post surgery
measure: To assess the occurrence of adverse events from GPi/NBM DBS and occurrence of adverse events.
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: To assess the impact on health-related quality-of-life and various non-motor symptoms of PD
timeFrame: 1 year
measure: To use neuroimaging biomarkers (MEG and FDG-PET) to examine localized effects of NBM stimulation
timeFrame: with NBM turned on and off, 22 and 30 weeks after surgery respectively
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
Study officials:
affiliation: University of Toronto
name: Alfonso Fasano, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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