Combined STN and NBM Deep Brain Stimulation for Mild Cognitive Impairment in Parkinson's Disease

February 8, 2024 updated by: Helen M. Bronte-Stewart

Neurostimulation of the Nucleus Basalis of Meynert for the Cognitive-Motor Syndrome in Parkinson's Disease

The goal of this clinical trial is to evaluate the safety and tolerability of a novel deep brain stimulation (DBS) of the Subthalamic Nucleus (STN) and Nucleus Basalis of Meynert (NBM) to treat cognitive and cognitive-motor symptoms in individuals with Parkinson's disease. The main question it aims to answer is:

Is a combined deep brain stimulation approach targeting the STN and NBM with four DBS leads safe and tolerable for cognitive and cognitive-motor symptoms in individuals with Parkinson's disease with Mild Cognitive Impairment. Ten participants are anticipated to be enrolled.

Participants will undergo a modification of the traditional STN DBS approach for motor symptoms of PD. In addition to the two leads placed within the STN, two additional leads will be placed with the NBM for treatment of cognitive and cognitive-motor symptoms. Novel stimulation patterns will be used within the NBM to target cognitive and cognitive-motor symptoms using an investigational software. Participants will be followed over two years while receiving this therapy with assessments at baseline and every six months. Assessments will include a combination of neuropsychological evaluations, cognitive assessments, motor tasks (including gait/walking), and questionnaires to evaluate the treatment. Two different surgical trajectories will be used, with half the cohort randomized to each group. This will allow comparison of the impact of surgical trajectory on the intervention.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

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 Contact

Study Locations

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of Parkinson's disease (PD)
  • Approved (or planning on) for subthalamic nucleus (STN) deep brain stimulation (DBS)
  • Willingness to withdraw from clinical medication regimen when necessary for research visits
  • Ability to provide informed consent

Exclusion Criteria:

  • Dementia
  • Unstable medical, psychiatric conditions including significant untreated depression, history of suicidal attempt, or current suicide ideation
  • History of seizures
  • Pregnant
  • Requires MRI
  • Unable to walk 100 feet without an assistive device

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
Experimental: Vertical Nuclear Trajectory
Participants will receive combined STN + NBM DBS. The lead placed within the NBM will use a vertical trajectory targeting the nucleus itself.
Device: Combined STN+NBM DBS
This intervention is a 4-lead deep brain stimulation approach targeting the Subthalamic Nucleus (STN) and Nucleus Basalis of Meynert (NBM)
Experimental: Lateral NBM Bundle Trajectory
Participants will receive combined STN + NBM DBS. The lead placed within the NBM will use a lateral trajectory targeting the lateral efferent bundle from the NBM
Device: Combined STN+NBM DBS
This intervention is a 4-lead deep brain stimulation approach targeting the Subthalamic Nucleus (STN) and Nucleus Basalis of Meynert (NBM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: From baseline to 1 year into treatment
Any untoward medical occurrence that occurs during this study whether or not considered related to the study device, study procedures, or study requirements that is identified or worsens during the duration of the study
From baseline to 1 year into treatment
Swing Time Coefficient of Variation
Time Frame: From baseline to 1 year into treatment
Swing time variability will be measured using the dual force plates in the SIP task and IMUs for TBC. It is defined as the mean swing time coefficient of variation (CV) of both legs.
From baseline to 1 year into treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Time Freezing
Time Frame: From baseline to 1 year into treatment
Duration of freezing episodes during SIP will be measured using IMUs and force plates using a validated offline algorithm.
From baseline to 1 year into treatment
Stride Time Coefficient of Variation
Time Frame: From baseline to 1 year into treatment
Stride time coefficient of variation will be measured using the dual force plates in the SIP task and IMUs. Stride time coefficient of variation is defined as the mean stride time coefficient of variation (CV) of both legs. A greater stride time CV is indicative of less rhythmic gait/stepping.
From baseline to 1 year into treatment
Shank Angular Velocity
Time Frame: From baseline to 1 year into treatment
Shank angular velocity will be measured from IMUs work on the participant's leg/ankle. Reductions in this value are indicative of FOG and gait impairment.
From baseline to 1 year into treatment
Tapping Speed
Time Frame: From baseline to 1 year into treatment
The interstrike-interval of alternating tapping will be measured using an engineered piano keyboard. A higher interstrike-interval indicates slower tapping
From baseline to 1 year into treatment
Tapping Rhythmicity
Time Frame: From baseline to 1 year into treatment
The variability of the interstrike-interval of alternating tapping, as quantified by the coefficient of variation, will be measured using an engineered piano keyboard. A higher coefficient of variation indicates worse rhythmicity
From baseline to 1 year into treatment
MDS-UPDRS III Score
Time Frame: From baseline to 1 year into treatment
PD symptoms will be assessed clinically using the MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Section III. This is a motor examination to evaluate speech, facial expression, tremor at rest, action or postural tremor of hands, rigidity, finger taps, hand movements, rapid alternating movement of hands, leg agility, arising from chair, posture, gait, freezing of gait, posture, body bradykinesia, and postural stability. Each item is scored on a scale from 0 (normal) to 4 (severe), with the total possible score ranging from 0 to 132.
From baseline to 1 year into treatment
SAT Score
Time Frame: From baseline to 1 year into treatment
Each trial of the SAT will be categorized as a Hit (H), Miss (M), or False Alarm (FA). The SAT score is defined as ((H - FA) / [2× (H + FA) - (H + FA)2]), which ranges from - 1.0 (100% incorrect performance; all misses and false alarms) to +1.0 (100% correct performance; all hits and correct rejections).
From baseline to 1 year into treatment
Percent False Positives
Time Frame: From baseline to 1 year into treatment
The percent of false positives during the SAT.
From baseline to 1 year into treatment
Percent Misses
Time Frame: From baseline to 1 year into treatment
The percent of misses of total trials during the SAT
From baseline to 1 year into treatment
Average + standard deviation of response time
Time Frame: From baseline to 1 year into treatment
The average and standard deviation of the response time during the SAT.
From baseline to 1 year into treatment
Goal-directed focus of attention
Time Frame: From baseline to 1 year into treatment
Hit rate during the first minute in the no- distractor condition for the CTET.
From baseline to 1 year into treatment
Sustained attention
Time Frame: From baseline to 1 year into treatment
Hit rate change slope in no-distractor condition for the CTET.
From baseline to 1 year into treatment
Distractibility
Time Frame: From baseline to 1 year into treatment
Hit rate difference between no-distractor and distractor conditions for the CTET.
From baseline to 1 year into treatment
Parkinson's Disease - Cognitive Rating Scale (PD-CRS)
Time Frame: From baseline to 1 year into treatment
Cognitive scale composed of 9 tasks that assesses the full range of cognitive dysfunction in PD. It is a scale of 0 to 134, with 134 being the best score.
From baseline to 1 year into treatment
Montreal Cognitive Assessment (MoCA)
Time Frame: From baseline to 1 year into treatment
Total score to assess of this rapid screening test of different cognitive domains. It is a scale of 0 to 30, with 30 being the best score.
From baseline to 1 year into treatment
Trails A
Time Frame: From baseline to 1 year into treatment
The time it takes to complete the task and errors.
From baseline to 1 year into treatment
Trails B
Time Frame: From baseline to 1 year into treatment
The time it takes to complete the task and errors.
From baseline to 1 year into treatment
Symbol Digit Modalities (SDMT) Oral and Written
Time Frame: From baseline to 1 year into treatment
The summation of the number of correct substitutions within the 90 second interval.
From baseline to 1 year into treatment
visual puzzles from the Wechsler Adult Intelligence Scale-IV (WAIS-IV)
Time Frame: From baseline to 1 year into treatment
Percentile of performance on visual puzzles for participant's demographic.
From baseline to 1 year into treatment
Judgement of Line Orientation
Time Frame: From baseline to 1 year into treatment
Percentile of performance on judgement of line orientation for participant's demographic.
From baseline to 1 year into treatment
Patient Health Questionnaire-9 (PHQ-9)
Time Frame: From baseline to 1 year into treatment
Total score on questionnaire regarding participant's mood the last 2 weeks. The scale ranges from 0 to 27 with a score of 27 indicating the most severe symptoms.
From baseline to 1 year into treatment
General Anxiety Disorder-7 (GAD-7)
Time Frame: From baseline to 1 year into treatment
Total score on questionnaire regarding participant's anxiety the last two weeks.The scale ranges from 0 to 21 with a score of 21 indicating the most severe symptoms.
From baseline to 1 year into treatment
MDS-UPDRS I
Time Frame: From baseline to 1 year into treatment
Total score evaluating the non-motor aspects of experiences of daily living. It is a scale from 0 to 52 with 52 being the most severe symptoms.
From baseline to 1 year into treatment
MDS-UPDRS II
Time Frame: From baseline to 1 year into treatment
Total score evaluating the motor aspects of experiences of daily living. It is a scale from 0 to 52 with 52 being the most severe symptoms.
From baseline to 1 year into treatment
MDS-UPDRS IV
Time Frame: From baseline to 1 year into treatment
Total score of motor complications experienced by the participant. It is a scale from 0 to 24 with 24 being the most severe symptoms.
From baseline to 1 year into treatment
Neuropsychiatric Inventory (NPI)
Time Frame: From baseline to 1 year into treatment
Total score for symptom severity and distress via questionnaire. It is a scale from 0 to 60 with 60 indicating worse symptoms.
From baseline to 1 year into treatment
Parkinson's Disease Questionnaire-39 (PDQ-39)
Time Frame: From baseline to 1 year into treatment
Total score for Parkinson's disease-specific health related quality over the last month across 8 quality of life dimensions assessed via questionnaire. Score ranges from 0 to 100 with 100 indicating more symptoms and problems.
From baseline to 1 year into treatment
Caregiver Burden Assessment
Time Frame: From baseline to 1 year into treatment
Total score on caregiver self-report to assess the stress-levels of family caregivers. It is a scale from 0 to 88 with higher scores indicating greater or worse burden.
From baseline to 1 year into treatment

Collaborators and Investigators

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

Sponsor

Helen M. Bronte-Stewart

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Helen M Bronte-Stewart, MD MSE, Stanford University

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 (Estimated)

February 1, 2024

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

July 19, 2023

First Submitted That Met QC Criteria

July 27, 2023

First Posted (Actual)

August 1, 2023

Study Record Updates

Last Update Posted (Actual)

February 12, 2024

Last Update Submitted That Met QC Criteria

February 8, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 70608
  • UG3NS128150 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified data will be uploaded to the Data Archive for the BRAIN Initiative (DABI).

IPD Sharing Time Frame

The IPD is anticipated to be available in approximately three months after study completion

IPD Sharing Access Criteria

DABI is openly available

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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