Simultaneous DBS of the GPi and the NBM in Patients With Parkinson's Disease and Mild Cognitive Impairment

April 1, 2022 updated by: University of Sao Paulo General Hospital

Simultaneous Deep Brain Stimulation of the Globus Pallidus Internus and the Nucleus Basalis of Meynert in Patients With Parkinson's Disease and Mild Cognitive Impairment

Phase 1 study evaluating the safety of combined bilateral globus pallidus internus (GPi) and nucleus basalis of Meynert (NBM) stimulation in treating levodopa responsive motor symptoms of Parkinsonism and cognitive dysfunction, respectively, in patients with moderate to advanced Parkinson's disease having mild cognitive impairment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study aims to provide a proof of safety of combined bilateral Globus Pallidus internus (GPi) and Nucleus Basalis of Meynert (NBM) stimulation in patients with moderate to advanced Parkinson's disease having mild cognitive impairment.

GPi stimulation with high-frequency ameliorates the cardinal motor symptoms and motor complications in Parkinson's disease patients, and this present study also wants to determine if additional NBM stimulation, with low-frequency stimulation, improves or slows progression of cognitive decline in patients with moderate to advanced Parkinson's disease having mild cognitive impairment, and to evaluate the effect of NBM stimulation on gait and balance impairment.

Study Design: Prospective single center Phase 1 study with double-blind randomized delayed activation of basal nucleus of Meynert neurostimulation (staggered onset design).

Planned Number of Subjects: 10 patients.

Planned Number of Sites / Countries: Single center in Brazil.

Study schedule:

  • Presurgical baseline evaluation (motor on and off medication state; cognitive testing in best motor on state).
  • DBS Implant Procedure.
  • Postsurgical baseline evaluation (motor off state; cognitive testing in best motor on state) at 3±1 weeks after surgery and activation of globus pallidus internus neurostimulation using individualized stimulation parameters after a standard monopolar review.
  • Regular adjustments of the GPi stimulation parameters aiming at the best motor improvement.
  • Visit 1 (16 weeks after activation of GPi neurostimulation): motor off medication + GPi stimulation state, cognitive testing in on medication + GPi stimulation state. Randomization and blinded activation of NBM neurostimulation according to a 1:1 scheme.
  • Visit 2 (16 weeks after randomization): motor off and on medication + stimulation state (GPi stimulation ± NBM stimulation); cognitive testing in motor on medication + stimulation state (GPi stimulation ± NBM stimulation). Activation of NBM neurostimulation in all patients.
  • Visit 3 (16 weeks after activation of NBM stimulation in all patients): motor off and on medication + GPi and NBM stimulation state; cognitive testing in motor on medication + GPi and NBM stimulation state.
  • Annual follow-up visit for up to 5 years after activation of NBM stimulation.

Study Type

Interventional

Enrollment (Anticipated)

10

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

  • Brazil
      • São Paulo, Brazil, 05403000
        • Recruiting
        • University of Sao Paulo General Hospital
        • Contact:
        • Contact:

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

50 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age at the time of enrollment: 50 - 75 years.
  • Diagnosis of idiopathic PD according to Movement Disorders Society (MDS) criteria (Albanese et al., 2017).
  • Mild cognitive impairment (MCI) related to Parkinson's disease according to MDS criteria. (Livtan et al. 2012).
  • Duration of bilateral idiopathic PD: ≥ 5 years of motor symptoms.
  • Modified Hoehn and Yahr stage ≥ 2 on off medication state.
  • UPDRS subset III (motor) ≥ 30 points on off medication state.
  • Levodopa must improve PD symptoms by ≥ 30% in a levodopa challenge test, as measured by UPDRS subset III score.
  • Presence of motor complications related to Parkinson's disease.
  • Be willing and able to comply with all visits and study related procedures
  • Able to understand the study requirements and the treatment procedures and to provide written informed consent before any study-specific tests or procedures are performed.

Exclusion Criteria:

  • Alcohol or drug abuse.
  • Any significant psychiatric problems, including acute confusional state (delirium), ongoing psychosis, or clinically significant depression.
  • Contraindications for deep brain stimulation (DBS) surgery.
  • Heart failure, heart disease or any condition that contraindicates surgical procedures.
  • Pacemaker or other active implanted stimulators.
  • Clearly established Parkinson's disease dementia according to Movement Disorders Criteria.
  • Participation in another drug, device, or biologics trial concurrently.

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: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: GPi stimulation + NBM stimulation
effective neurostimulation of the Nucleus basalis Meynert combined with globus pallidus internus (GPi) stimulation using Vercise deep brain stimulation
Device: Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM.
Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM, at the same trajectory.
Device: GPi stimulation
Bilateral high-frequency neurostimulation of the GPi using a Vercise neurostimulation system
Device: NBM stimulation
Bilateral low-frequency neurostimulation of the NBM using a Vercise neurostimulation system
Sham Comparator: GPi stimulation + sham stimulation
ineffective neurostimulation of the Nucleus basalis Meynert combined with subthalamic nucleus (STN) stimulation using Vercise deep brain stimulation
Device: Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM.
Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM, at the same trajectory.
Device: GPi stimulation
Bilateral high-frequency neurostimulation of the GPi using a Vercise neurostimulation system
Device: Sham stimulation
Ineffective neurostimulation by setting 0mA output at the Vercise neurostimulation system

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of combined bilateral Globus Pallidus internus (GPi) and Nucleus Basalis of Meynert (NBM) stimulation in patients with moderate to advanced Parkinson's disease with mild cognitive impairment as determined by reported adverse events.
Time Frame: 36 weeks
Safety of combined bilateral GPi and NBM stimulation in patients with moderate to advanced Parkinson's disease having mild cognitive impairment as determined by reported adverse events.
36 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Parkinson's Disease - Cognitive Rating Scale (PD-CRS).
Time Frame: 36 weeks
This scale can range from 0 to 134, and higher scores mean a better outcome.
36 weeks
Change in Mattis Dementia Rating Scale.
Time Frame: 36 weeks
This scale can range from 0 to 144, and higher scores mean a better outcome.
36 weeks
Change in Verbal Fluency Battery.
Time Frame: 36 weeks
FAS and animals
36 weeks
Change in Trail Making Task.
Time Frame: 36 weeks
Trail Making Task Part A + B.
36 weeks
Change in Stroop Test.
Time Frame: 36 weeks
Stroop Test (Victoria Version).
36 weeks
Change in Symbol Digit Modalities Test.
Time Frame: 36 weeks
Digit symbol coding - WAIS.
36 weeks
Change in Parkinson's Disease Questionnaire for quality of life (PDQ-39).
Time Frame: 36 weeks
This questionnaire can range from 0 to 100%, and higher scores mean a worse outcome.
36 weeks
Change in Questionnaire of the EuroQol-group (EQ-5D-5L).
Time Frame: 36 weeks
This questionnaire can range from 0 to 25, and higher scores mean a worse outcome.
36 weeks
Change in Unified Parkinson's Disease Rating Scale section I (UPDRS I).
Time Frame: 36 weeks
This scale can range from 0 to 52, and higher scores mean a worse outcome.
36 weeks
Change in Unified Parkinson's Disease Rating Scale section II (UPDRS II).
Time Frame: 36 weeks
This scale can range from 0 to 52, and higher scores mean a worse outcome.
36 weeks
Change in Unified Parkinson's Disease Rating Scale section III (UPDRS III).
Time Frame: 36 weeks
This scale can range from 0 to 132, and higher scores mean a worse outcome.
36 weeks
Change in Unified Parkinson's Disease Rating Scale section IV (UPDRS IV).
Time Frame: 36 weeks
This scale can range from 0 to 24, and higher scores mean a worse outcome.
36 weeks
Change in objective assessment of gait measured by a sensor (MobilityLab) that assess step speed.
Time Frame: 36 weeks
36 weeks
Change in objective assessment of gait measured by a sensor (MobilityLab) that assess number of steps per minute.
Time Frame: 36 weeks
36 weeks
Change in objective assessment of gait measured by a sensor (MobilityLab) that assess distance between heels.
Time Frame: 36 weeks
36 weeks
Change in objective assessment of gait measured by a sensor (MobilityLab) that assess balance.
Time Frame: 36 weeks
36 weeks
Change in objective assessment of gait measured by Time Up and Go - Test 3 meters (TUG test 3M).
Time Frame: 36 weeks
36 weeks
Change in objective assessment of gait measured by Time Up and Go dual task - Test 3 meters (TUG dual task - test 3M).
Time Frame: 36 weeks
36 weeks
Change in objective assessment of gait measured by freezing of gait score (FOG score).
Time Frame: 36 weeks
36 weeks
Change in New Freezing of Gait Questionnaire (N-FOG).
Time Frame: 36 weeks
This questionnaire can range from 0 to 28, and higher scores mean a worse outcome.
36 weeks
Change in Falls Efficacy Scale International (FES-I).
Time Frame: 36 weeks
This questionnaire can range from 0 to 64, and higher scores mean a worse outcome.
36 weeks
Change in Activities-Specific Balance Confidence Scale (ABC scale).
Time Frame: 36 weeks
This scale can range from 0 to 100%, and higher scores mean a better outcome.
36 weeks
Change in Beck Depression Inventory (BDI).
Time Frame: 36 weeks
This inventory can range from 0 to 63, and higher scores mean a worse outcome.
36 weeks
Change in Beck Anxiety Inventory (BAI).
Time Frame: 36 weeks
This inventory can range from 0 to 63, and higher scores mean a worse outcome.
36 weeks
Change in Starkstein Apathy Scale.
Time Frame: 36 weeks
This scale can range from 0 to 42, and higher scores mean a worse outcome.
36 weeks
Change in Neuropsychiatric Inventory (NPI).
Time Frame: 36 weeks
36 weeks
Change in Ardouin Scale of Behavior in Parkinson's Disease.
Time Frame: 36 weeks
This scale can range from 0 to 84, and higher scores mean a worse outcome.
36 weeks

Collaborators and Investigators

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

Sponsor

University of Sao Paulo General Hospital

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)

July 20, 2021

Primary Completion (Anticipated)

August 1, 2023

Study Completion (Anticipated)

January 1, 2024

Study Registration Dates

First Submitted

March 14, 2022

First Submitted That Met QC Criteria

April 1, 2022

First Posted (Actual)

April 11, 2022

Study Record Updates

Last Update Posted (Actual)

April 11, 2022

Last Update Submitted That Met QC Criteria

April 1, 2022

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38865720.1.0000.0068

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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