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

November 1, 2022 updated by: Alfonso Fasano, University of Toronto

Multi-targets, Single-lead GPi+NBM DBS in Parkinson's Disease With Mild Cognitive Impairment

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 2S8
        • Toronto Western Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Device: 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.
Sham Comparator: 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.
Device: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in cognition after GPi/NBM DBS
Time Frame: at baseline and 6, 14, 22, 30 and 52 weeks post surgery
This will be measured by the ADAS-Cog 13, verbal fluency test and sustained attention task.
at baseline and 6, 14, 22, 30 and 52 weeks post surgery
Change in motor function (UPDRS)GPi/NBM DBS
Time Frame: at baseline and 6, 14, 22, 30 and 52 weeks post surgery
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive 65 item assessment of both motor and non-motor symptoms associated with Parkinson's Disease. Each symptom is rated on a 5-point scale (from 0 to 4), and the maximum total score is 199, indicating severe impairment from parkinson's disease.
at baseline and 6, 14, 22, 30 and 52 weeks post surgery
To assess the occurrence of adverse events from GPi/NBM DBS and occurrence of adverse events.
Time Frame: through study completion, an average of 1 year
We define an adverse event (AE) as any untoward medical occurrence that occurs in the course of this study whether or not considered related to the study device, study procedures or study requirements that is identified or worsens during the study.
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the impact on health-related quality-of-life and various non-motor symptoms of PD
Time Frame: 1 year
This is measured by the Parkinson's Disease Questionnaire, with a score range from 0 (never have difficulty) to 100 (always have difficulty), and with lower scores reflecting a better quality of life
1 year
To use neuroimaging biomarkers (MEG and FDG-PET) to examine localized effects of NBM stimulation
Time Frame: with NBM turned on and off, 22 and 30 weeks after surgery respectively
Region of interest analysis will be used to determine the localized effects of NBM in the surrounding structures and cortex for both MEG and PET imaging.
with NBM turned on and off, 22 and 30 weeks after surgery respectively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Toronto

Investigators

  • Principal Investigator: Alfonso Fasano, MD, PhD, University of Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 4, 2017

Primary Completion (Actual)

October 1, 2020

Study Completion (Actual)

March 1, 2021

Study Registration Dates

First Submitted

September 12, 2019

First Submitted That Met QC Criteria

September 26, 2020

First Posted (Actual)

September 30, 2020

Study Record Updates

Last Update Posted (Actual)

November 2, 2022

Last Update Submitted That Met QC Criteria

November 1, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-5400-B

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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