GPi+NBM DBS in Parkinson's Disease With Mild Cognitive Impairment (2T-DBS)

University of Toronto

Status: Completed

Conditions: Memory Disorders; Parkinson Disease

Treatments: Device: NBM stimulation using the Vercise device (Boston Scientific, Marlborough, Massachusetts, US)

Study type: Interventional

Funder types: Other

Identifiers

NCT04571112

17-5400-B

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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6 participants in 2 patient groups

NBM ON

Experimental group

Description:

The post-surgical double-blind cross-over phase with randomization will follow once programming settings are determined. Under constant GPi DBS, patients will receive NBM DBS active or sham for 8 weeks followed by an 8-week cross-over. The NBM ON arm will have constant NBM stimulation for 8 weeks.

Treatment:

Device: NBM stimulation using the Vercise device (Boston Scientific, Marlborough, Massachusetts, US)

NBM OFF

Sham Comparator group

Description:

The post-surgical double-blind cross-over phase with randomization will follow once programming settings are determined. Under constant GPi DBS, patients will receive NBM DBS active or sham for 8 weeks followed by an 8-week cross-over. The NBM OFF arm will have NBM stimulation turned off for 8 weeks.

Treatment:

Device: NBM stimulation using the Vercise device (Boston Scientific, Marlborough, Massachusetts, US)