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

Primary Purpose

Parkinson Disease, Mild Cognitive Impairment

Status

Recruiting

Phase

Not Applicable

Locations

Brazil

Study Type

Interventional

Intervention

Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM.

GPi stimulation

NBM stimulation

Sham stimulation

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinson's disease, Mild cognitive impairment, Globus Pallidus internus (GPi) Stimulation, Nucleus basalis of Meynert (NBM) Stimulation, Deep Brain Stimulation (DBS)

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of São Paulo General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

GPi stimulation + NBM stimulation

GPi stimulation + sham stimulation

Arm Description

effective neurostimulation of the Nucleus basalis Meynert combined with globus pallidus internus (GPi) stimulation using Vercise deep brain stimulation

ineffective neurostimulation of the Nucleus basalis Meynert combined with subthalamic nucleus (STN) stimulation using Vercise deep brain stimulation

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Change in Parkinson's Disease - Cognitive Rating Scale (PD-CRS).

This scale can range from 0 to 134, and higher scores mean a better outcome.

Change in Mattis Dementia Rating Scale.

This scale can range from 0 to 144, and higher scores mean a better outcome.

Change in Verbal Fluency Battery.

FAS and animals

Change in Trail Making Task.

Trail Making Task Part A + B.

Change in Stroop Test.

Stroop Test (Victoria Version).

Change in Symbol Digit Modalities Test.

Digit symbol coding - WAIS.

Change in Parkinson's Disease Questionnaire for quality of life (PDQ-39).

This questionnaire can range from 0 to 100%, and higher scores mean a worse outcome.

Change in Questionnaire of the EuroQol-group (EQ-5D-5L).

This questionnaire can range from 0 to 25, and higher scores mean a worse outcome.

Change in Unified Parkinson's Disease Rating Scale section I (UPDRS I).

This scale can range from 0 to 52, and higher scores mean a worse outcome.

Change in Unified Parkinson's Disease Rating Scale section II (UPDRS II).

This scale can range from 0 to 52, and higher scores mean a worse outcome.

Change in Unified Parkinson's Disease Rating Scale section III (UPDRS III).

This scale can range from 0 to 132, and higher scores mean a worse outcome.

Change in Unified Parkinson's Disease Rating Scale section IV (UPDRS IV).

This scale can range from 0 to 24, and higher scores mean a worse outcome.

Change in objective assessment of gait measured by a sensor (MobilityLab) that assess step speed.

Change in objective assessment of gait measured by a sensor (MobilityLab) that assess number of steps per minute.

Change in objective assessment of gait measured by a sensor (MobilityLab) that assess distance between heels.

Change in objective assessment of gait measured by a sensor (MobilityLab) that assess balance.

Change in objective assessment of gait measured by Time Up and Go - Test 3 meters (TUG test 3M).

Change in objective assessment of gait measured by Time Up and Go dual task - Test 3 meters (TUG dual task - test 3M).

Change in objective assessment of gait measured by freezing of gait score (FOG score).

Change in New Freezing of Gait Questionnaire (N-FOG).

This questionnaire can range from 0 to 28, and higher scores mean a worse outcome.

Change in Falls Efficacy Scale International (FES-I).

This questionnaire can range from 0 to 64, and higher scores mean a worse outcome.

Change in Activities-Specific Balance Confidence Scale (ABC scale).

This scale can range from 0 to 100%, and higher scores mean a better outcome.

Change in Beck Depression Inventory (BDI).

This inventory can range from 0 to 63, and higher scores mean a worse outcome.

Change in Beck Anxiety Inventory (BAI).

This inventory can range from 0 to 63, and higher scores mean a worse outcome.

Change in Starkstein Apathy Scale.

This scale can range from 0 to 42, and higher scores mean a worse outcome.

Change in Neuropsychiatric Inventory (NPI).

Change in Ardouin Scale of Behavior in Parkinson's Disease.

This scale can range from 0 to 84, and higher scores mean a worse outcome.

Full Information

NCT ID

NCT05320523

First Posted

March 14, 2022

Last Updated

April 1, 2022

Sponsor

University of Sao Paulo General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05320523

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Recruiting

Study Start Date

July 20, 2021 (Actual)

Primary Completion Date

August 2023 (Anticipated)

Study Completion Date

January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Sao Paulo General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease, Mild Cognitive Impairment

Keywords

Parkinson's disease, Mild cognitive impairment, Globus Pallidus internus (GPi) Stimulation, Nucleus basalis of Meynert (NBM) Stimulation, Deep Brain Stimulation (DBS)

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GPi stimulation + NBM stimulation

Arm Type

Active Comparator

Arm Description

effective neurostimulation of the Nucleus basalis Meynert combined with globus pallidus internus (GPi) stimulation using Vercise deep brain stimulation

Arm Title

GPi stimulation + sham stimulation

Arm Type

Sham Comparator

Arm Description

ineffective neurostimulation of the Nucleus basalis Meynert combined with subthalamic nucleus (STN) stimulation using Vercise deep brain stimulation

Intervention Type

Device

Intervention Name(s)

Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM.

Intervention Description

Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM, at the same trajectory.

Intervention Type

Device

Intervention Name(s)

GPi stimulation

Intervention Description

Bilateral high-frequency neurostimulation of the GPi using a Vercise neurostimulation system

Intervention Type

Device

Intervention Name(s)

NBM stimulation

Intervention Description

Bilateral low-frequency neurostimulation of the NBM using a Vercise neurostimulation system

Intervention Type

Device

Intervention Name(s)

Sham stimulation

Intervention Description

Ineffective neurostimulation by setting 0mA output at the Vercise neurostimulation system

Primary Outcome Measure Information:

Title

Description

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.

Time Frame

36 weeks

Secondary Outcome Measure Information:

Title

Change in Parkinson's Disease - Cognitive Rating Scale (PD-CRS).

Description

This scale can range from 0 to 134, and higher scores mean a better outcome.

Time Frame

36 weeks

Title

Change in Mattis Dementia Rating Scale.

Description

This scale can range from 0 to 144, and higher scores mean a better outcome.

Time Frame

36 weeks

Title

Change in Verbal Fluency Battery.

Description

FAS and animals

Time Frame

36 weeks

Title

Change in Trail Making Task.

Description

Trail Making Task Part A + B.

Time Frame

36 weeks

Title

Change in Stroop Test.

Description

Stroop Test (Victoria Version).

Time Frame

36 weeks

Title

Change in Symbol Digit Modalities Test.

Description

Digit symbol coding - WAIS.

Time Frame

36 weeks

Title

Change in Parkinson's Disease Questionnaire for quality of life (PDQ-39).

Description

This questionnaire can range from 0 to 100%, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Questionnaire of the EuroQol-group (EQ-5D-5L).

Description

This questionnaire can range from 0 to 25, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Unified Parkinson's Disease Rating Scale section I (UPDRS I).

Description

This scale can range from 0 to 52, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Unified Parkinson's Disease Rating Scale section II (UPDRS II).

Description

This scale can range from 0 to 52, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Unified Parkinson's Disease Rating Scale section III (UPDRS III).

Description

This scale can range from 0 to 132, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Unified Parkinson's Disease Rating Scale section IV (UPDRS IV).

Description

This scale can range from 0 to 24, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in objective assessment of gait measured by a sensor (MobilityLab) that assess step speed.

Time Frame

36 weeks

Title

Change in objective assessment of gait measured by a sensor (MobilityLab) that assess number of steps per minute.

Time Frame

36 weeks

Title

Change in objective assessment of gait measured by a sensor (MobilityLab) that assess distance between heels.

Time Frame

36 weeks

Title

Change in objective assessment of gait measured by a sensor (MobilityLab) that assess balance.

Time Frame

36 weeks

Title

Change in objective assessment of gait measured by Time Up and Go - Test 3 meters (TUG test 3M).

Time Frame

36 weeks

Title

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

Title

Change in objective assessment of gait measured by freezing of gait score (FOG score).

Time Frame

36 weeks

Title

Change in New Freezing of Gait Questionnaire (N-FOG).

Description

This questionnaire can range from 0 to 28, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Falls Efficacy Scale International (FES-I).

Description

This questionnaire can range from 0 to 64, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Activities-Specific Balance Confidence Scale (ABC scale).

Description

This scale can range from 0 to 100%, and higher scores mean a better outcome.

Time Frame

36 weeks

Title

Change in Beck Depression Inventory (BDI).

Description

This inventory can range from 0 to 63, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Beck Anxiety Inventory (BAI).

Description

This inventory can range from 0 to 63, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Starkstein Apathy Scale.

Description

This scale can range from 0 to 42, and higher scores mean a worse outcome.

Time Frame

36 weeks

Title

Change in Neuropsychiatric Inventory (NPI).

Time Frame

36 weeks

Title

Change in Ardouin Scale of Behavior in Parkinson's Disease.

Description

This scale can range from 0 to 84, and higher scores mean a worse outcome.

Time Frame

36 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Facility Information:

Facility Name

University of São Paulo General Hospital

City

São Paulo

ZIP/Postal Code

05403000

Country

Brazil

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Rubens G Cury, MD, PhD

Phone

+551126617877

rubens_cury@usp.br

First Name & Middle Initial & Last Name & Degree

Ana Paula S Bertholo, MD

Phone

+5511998691919

anapaulabertolo@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29255885

Citation

Gratwicke J, Zrinzo L, Kahan J, Peters A, Beigi M, Akram H, Hyam J, Oswal A, Day B, Mancini L, Thornton J, Yousry T, Limousin P, Hariz M, Jahanshahi M, Foltynie T. Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2018 Feb 1;75(2):169-178. doi: 10.1001/jamaneurol.2017.3762.

Results Reference

result

PubMed Identifier

30630160

Citation

Nombela C, Lozano A, Villanueva C, Barcia JA. Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome. Dement Geriatr Cogn Disord. 2019;47(1-2):19-28. doi: 10.1159/000493094. Epub 2019 Jan 10.

Results Reference

result

PubMed Identifier

24777384

Citation

Sankar T, Lipsman N, Lozano AM. Deep brain stimulation for disorders of memory and cognition. Neurotherapeutics. 2014 Jul;11(3):527-34. doi: 10.1007/s13311-014-0275-0.

Results Reference

result

PubMed Identifier

24798585

Citation

Kuhn J, Hardenacke K, Lenartz D, Gruendler T, Ullsperger M, Bartsch C, Mai JK, Zilles K, Bauer A, Matusch A, Schulz RJ, Noreik M, Buhrle CP, Maintz D, Woopen C, Haussermann P, Hellmich M, Klosterkotter J, Wiltfang J, Maarouf M, Freund HJ, Sturm V. Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia. Mol Psychiatry. 2015 Mar;20(3):353-60. doi: 10.1038/mp.2014.32. Epub 2014 May 6.

Results Reference

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PubMed Identifier

19506141

Citation

Freund HJ, Kuhn J, Lenartz D, Mai JK, Schnell T, Klosterkoetter J, Sturm V. Cognitive functions in a patient with Parkinson-dementia syndrome undergoing deep brain stimulation. Arch Neurol. 2009 Jun;66(6):781-5. doi: 10.1001/archneurol.2009.102. Erratum In: Arch Neurol. 2011 Apr;68(4):421.

Results Reference

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PubMed Identifier

33382126

Citation

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Results Reference

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PubMed Identifier

23943367

Citation

Muller ML, Bohnen NI. Cholinergic dysfunction in Parkinson's disease. Curr Neurol Neurosci Rep. 2013 Sep;13(9):377. doi: 10.1007/s11910-013-0377-9.

Results Reference

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PubMed Identifier

32334074

Citation

Gratwicke J, Zrinzo L, Kahan J, Peters A, Brechany U, McNichol A, Beigi M, Akram H, Hyam J, Oswal A, Day B, Mancini L, Thornton J, Yousry T, Crutch SJ, Taylor JP, McKeith I, Rochester L, Schott JM, Limousin P, Burn D, Rossor MN, Hariz M, Jahanshahi M, Foltynie T. Bilateral nucleus basalis of Meynert deep brain stimulation for dementia with Lewy bodies: A randomised clinical trial. Brain Stimul. 2020 Jul-Aug;13(4):1031-1039. doi: 10.1016/j.brs.2020.04.010. Epub 2020 Apr 22.

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Citation

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Citation

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Learn more about this trial

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

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