Deep Brain Stimulation of the nbM to Treat Mild Cognitive Impairment in Parkinson's Disease

Back to results

Primary Purpose

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

stimulation ON

stimulation OFF

About this trial

This is an interventional treatment trial for Parkinson's Disease

Eligibility Criteria

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

Inclusion Criteria:

Informed consent signed by the subject.
Parkinson's disease per UK Parkinson's Disease Society Brain Bank (Queens Square) criteria
Diagnosis of PD-MCI, amnestic subtype per MDS criteria (Level II assessment)
DBS candidate for GPi targeting per the consensus committee
50 - 75 years of age
Primary English speaking
Minimum of 10 years of education
Motorically and cognitively capable of completing evaluations and consent
Medically cleared for surgery and anesthesia
Subject must be on stable doses of any medication used to treat PD or cognition for 3 months prior to study entry
Female subjects with child-bearing potential have a negative serum pregnancy test prior to DBS surgery -

Exclusion Criteria:

Dementia per DSM-V criteria
Condition precluding MRI
History of supraspinal CNS disease other than PD
Medical condition or required medication compromising cognition
Alcohol use of more than 4 drinks per day
Currently uncontrolled moderate-severe depression (BDI>20)
History of suicide attempt in the year preceding study screening
History of schizophrenia, delusions, or currently uncontrolled visual hallucinations
Use of cholinesterase inhibitor
Subjects who require rTMS, ECT, diathermy, or repeat MRI procedures to treat a medical condition.
Subjects with a history of seizure disorder
Subjects who have made a suicide attempt within the prior year,
Subjects with any medical contraindications to undergoing DBS surgery (eg, infection, coagulopathy, or significant cardiac or other medical risk factors for surgery)
Subjects with an implanted stimulator such as a cardiac pacemaker, defibrillator, neurostimulator and cochlear implant
Subjects who are pregnant or nursing.

Sites / Locations

St. Joseph's Hospital and Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

nbM stimulation ON for 3 months (GPi also on)

nbM stimulation OFF for 3 months (GPi is on)

Arm Description

Subjects will undergo activation of GPi and nbM electrodes The GPi's will be stimulated to achieve improvement in motor function. There is a double blind evaluation of DBS-nbM stimulation. Subjects will be those with nbM stimulation ON for a period of 3 months (GPi also on). No usual treatment is withheld. PD drug doses will be stable unless disabling dyskinesias warrants a reduction of medication. After initial 3 months period of stimulation subject will undergo a repeat of neuropsychological testing and Motor Unified Parkinson's Disease Rating Scale (UPDRS) rating prior to switching group assignment (cross-over). There will be a 2 day wash-out period of nbM stimulation for all subjects (both the On and Off groups) in order to minimize subject bias. Then, the subjects will undergo additional brief neuropsychological testing to asses for carry over effects. The subjects will then be switched to the alternate nbM stimulation group (cross-over) from their previous 3 month period.

Subjects will undergo activation of GPi and nbM electrodes The GPi's will be stimulated to achieve improvement in motor function. There is a double blind evaluation of DBS-nbM stimulation. Subjects will be those with nbM stimulation OFF for a period of 3 months (GPi is on). No usual treatment is withheld. PD drug doses will be stable during blinded parts of the assessment unless disabling dyskinesias warrants a reduction of medication. After initial 3 months period of stimulation subject will undergo a repeat of neuropsychological testing and Motor UPDRS rating prior to switching group assignment (cross-over). There will be a 2 day wash-out period of nbM stimulation for all subjects (both the On and Off groups) in order to minimize subject bias. Then, the subjects will undergo additional brief neuropsychological testing to asses for carry over effects. The subjects will then be switched to the alternate nbM stimulation group (cross-over) from their previous 3 month period.

Outcomes

Primary Outcome Measures

Evaluate safety of DBS-nbM

Evaluate safety through collection of adverse events at weeks 4, 16, 28, 52 and months 24 and 36.

Secondary Outcome Measures

Stability or improvement of cognitive symptoms

Administration of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) administered at Week 52 and Months 24 and 36. A clinically meaningful change is indicated by a 4 point change in ADAS-Cog.

Full Information

NCT ID

NCT02924194

First Posted

September 30, 2016

Last Updated

September 20, 2021

Sponsor

St. Joseph's Hospital and Medical Center, Phoenix

Collaborators

Barrow Neurological Foundation

1. Study Identification

Unique Protocol Identification Number

NCT02924194

Brief Title

Deep Brain Stimulation of the nbM to Treat Mild Cognitive Impairment in Parkinson's Disease

Official Title

Deep Brain Stimulation (DBS) of the Nucleus Basalis of Meynert (nbM) to Treat Parkinson's Patients With Mild Cognitive Impairment, Amnestic Subtype

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Terminated

Why Stopped

The study was halted prematurely due to lack of interested participants.

Study Start Date

September 2016 (undefined)

Primary Completion Date

April 15, 2021 (Actual)

Study Completion Date

April 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Joseph's Hospital and Medical Center, Phoenix

Collaborators

Barrow Neurological Foundation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of deep brain stimulation of the nucleus basalis of Meynert (also called the "nbM") at improving memory in Parkinson's disease patients with mild cognitive impairments and memory difficulties. Patients with Parkinson's disease (PD) that are eligible for Deep Brain Stimulation (DBS) therapy for improvement of their motor symptoms and with evidence of mild cognitive impairments and memory difficulties will be enrolled.

Detailed Description

This is a prospective, double-blind (patient and neuropsychologist), randomized, cross-over study to evaluate the safety of deep brain stimulation of the nucleus basalis of Meynert (nbM) in Parkinson's disease (PD) patients with mild cognitive impairment (PD-MCI) who are undergoing globus pallidus internus (GPi) stimulation for their motor symptoms. Six patients with PD who are eligible for GPi DBS for improvement of their motor symptoms and who have a clinical diagnosis of PD-MCI (amnestic, single or multiple domain) per Movement Disorder Society (MDS) criteria will be enrolled and implanted with bilateral electrodes in in the nbM in addition to the globus pallidus internus (GPi). Conventional stereotactic implantation of the electrodes will be guided by intraoperative computerized tomography (CT) and magnetic resonance tomography (MRT).

6. Conditions and Keywords

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

Parkinson's Disease, Mild Cognitive Impairment

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

nbM stimulation ON for 3 months (GPi also on)

Arm Type

Experimental

Arm Description

Subjects will undergo activation of GPi and nbM electrodes The GPi's will be stimulated to achieve improvement in motor function. There is a double blind evaluation of DBS-nbM stimulation. Subjects will be those with nbM stimulation ON for a period of 3 months (GPi also on). No usual treatment is withheld. PD drug doses will be stable unless disabling dyskinesias warrants a reduction of medication. After initial 3 months period of stimulation subject will undergo a repeat of neuropsychological testing and Motor Unified Parkinson's Disease Rating Scale (UPDRS) rating prior to switching group assignment (cross-over). There will be a 2 day wash-out period of nbM stimulation for all subjects (both the On and Off groups) in order to minimize subject bias. Then, the subjects will undergo additional brief neuropsychological testing to asses for carry over effects. The subjects will then be switched to the alternate nbM stimulation group (cross-over) from their previous 3 month period.

Arm Title

nbM stimulation OFF for 3 months (GPi is on)

Arm Type

Experimental

Arm Description

Subjects will undergo activation of GPi and nbM electrodes The GPi's will be stimulated to achieve improvement in motor function. There is a double blind evaluation of DBS-nbM stimulation. Subjects will be those with nbM stimulation OFF for a period of 3 months (GPi is on). No usual treatment is withheld. PD drug doses will be stable during blinded parts of the assessment unless disabling dyskinesias warrants a reduction of medication. After initial 3 months period of stimulation subject will undergo a repeat of neuropsychological testing and Motor UPDRS rating prior to switching group assignment (cross-over). There will be a 2 day wash-out period of nbM stimulation for all subjects (both the On and Off groups) in order to minimize subject bias. Then, the subjects will undergo additional brief neuropsychological testing to asses for carry over effects. The subjects will then be switched to the alternate nbM stimulation group (cross-over) from their previous 3 month period.

Intervention Type

Device

Intervention Name(s)

stimulation ON

Intervention Description

The system used in the study includes the Model 37601 Activa PC stimulator, Model 3387 Lead and Model 37085 Extension, all manufactured and commercially available by Medtronic, Inc. Collectively, these devices will be referred to as "the DBS System". The DBS System is commercially available in the United States and was approved by FDA on July 31, 1997 under PMA P960009. It is indicated for deep brain stimulation for the treatment of symptoms of Parkinson's disease and essential tremor.

Intervention Type

Device

Intervention Name(s)

stimulation OFF

Intervention Description

The system used in the study includes the Model 37601 Activa PC stimulator, Model 3387 Lead and Model 37085 Extension, all manufactured and commercially available by Medtronic, Inc. Collectively, these devices will be referred to as "the DBS System". The DBS System is commercially available in the United States and was approved by FDA on July 31, 1997 under PMA P960009. It is indicated for deep brain stimulation for the treatment of symptoms of Parkinson's disease and essential tremor.

Primary Outcome Measure Information:

Title

Evaluate safety of DBS-nbM

Description

Evaluate safety through collection of adverse events at weeks 4, 16, 28, 52 and months 24 and 36.

Time Frame

Month 36

Secondary Outcome Measure Information:

Title

Stability or improvement of cognitive symptoms

Description

Administration of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) administered at Week 52 and Months 24 and 36. A clinically meaningful change is indicated by a 4 point change in ADAS-Cog.

Time Frame

Month 36

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Informed consent signed by the subject. Parkinson's disease per UK Parkinson's Disease Society Brain Bank (Queens Square) criteria Diagnosis of PD-MCI, amnestic subtype per MDS criteria (Level II assessment) DBS candidate for GPi targeting per the consensus committee 50 - 75 years of age Primary English speaking Minimum of 10 years of education Motorically and cognitively capable of completing evaluations and consent Medically cleared for surgery and anesthesia Subject must be on stable doses of any medication used to treat PD or cognition for 3 months prior to study entry Female subjects with child-bearing potential have a negative serum pregnancy test prior to DBS surgery - Exclusion Criteria: Dementia per DSM-V criteria Condition precluding MRI History of supraspinal CNS disease other than PD Medical condition or required medication compromising cognition Alcohol use of more than 4 drinks per day Currently uncontrolled moderate-severe depression (BDI>20) History of suicide attempt in the year preceding study screening History of schizophrenia, delusions, or currently uncontrolled visual hallucinations Use of cholinesterase inhibitor Subjects who require rTMS, ECT, diathermy, or repeat MRI procedures to treat a medical condition. Subjects with a history of seizure disorder Subjects who have made a suicide attempt within the prior year, Subjects with any medical contraindications to undergoing DBS surgery (eg, infection, coagulopathy, or significant cardiac or other medical risk factors for surgery) Subjects with an implanted stimulator such as a cardiac pacemaker, defibrillator, neurostimulator and cochlear implant Subjects who are pregnant or nursing.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Francisco A Ponce, MD

Organizational Affiliation

Barrow Brain and Spine

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Joseph's Hospital and Medical Center

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85205-6118

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

No

Parkinson's Disease, Mild Cognitive Impairment

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial