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Completed

NCT Number: NCT04571112

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.

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Key information

Conditions

Parkinson Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Memory Disorders Movement Disorders Nervous System Diseases Neurobehavioral Manifestations Neurodegenerative Diseases Neurologic Manifestations Parkinsonian Disorders Pathological Conditions, Signs and Symptoms Signs and Symptoms Synucleinopathies

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)
  • PD fulfilling standard criteria for bilateral GPi DBS surgery
  • Patient's ability to provide informed consent and comply with study protocol.

Exclusion criteria

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

Other conditions contraindicating DBS, PET scanning or MRI scanning.

Treatment and study plan

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

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.

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. 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

  2. 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.

Sponsors and collaborators

Lead sponsor

University of Toronto

Other

Registry information

Official study title

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

Acronym: 2T-DBS

Important dates

Study start
2017
Primary completion
2020
Study completion
2021
First posted
Sep 30, 2020
Registry last updated
Nov 2, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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