GPi+NBM DBS in Parkinson's Disease With Mild Cognitive Impairment

NCT ID: NCT04571112

Last Updated: 2022-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-04

Study Completion Date

2021-03-01

Brief Summary

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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

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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.

Conditions

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Parkinson Disease Memory Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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 Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
* 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. Then, patients will enter a post-surgical open-label follow-up phase during which they will receive GPi+NBM DBS.
* The outcomes assessor is blinded to the whether the NBM DBS is active to avoid bias while analyzing the data

Study Groups

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NBM ON

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.

Group Type EXPERIMENTAL

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

Intervention Type DEVICE

This will either be turned on or off depending on the arm which the patient is randomized to. After 8-weeks, the subject will switch arms for another 8-weeks.

NBM OFF

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.

Group Type SHAM_COMPARATOR

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

Intervention Type DEVICE

This will either be turned on or off depending on the arm which the patient is randomized to. After 8-weeks, the subject will switch arms for another 8-weeks.

Interventions

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

This will either be turned on or off depending on the arm which the patient is randomized to. After 8-weeks, the subject will switch arms for another 8-weeks.

Intervention Type DEVICE

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Toronto

OTHER

Sponsor Role lead

Responsible Party

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Alfonso Fasano

Dr. Alfonso Fasano, MD, PhD, Professor, Department of Medicine, Division of Neurology at University of Toronto, Toronto Western Hospital

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alfonso Fasano, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

Locations

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Toronto Western Hospital

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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Other Identifiers

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17-5400-B

Identifier Type: -

Identifier Source: org_study_id

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