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

NCT02924194 | Terminated DMC

• 1 other identifier: PHX-16-0141-30-06
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Evaluate safety of DBS-nbM

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

  Month 36

Secondary Outcomes (1)

• Stability or improvement of cognitive symptoms

  Month 36

Study Arms (2)

nbM stimulation ON for 3 months (GPi also on)

EXPERIMENTAL

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.

Device: stimulation ON

nbM stimulation OFF for 3 months (GPi is on)

EXPERIMENTAL

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.

Device: stimulation OFF

Interventions

stimulation ON DEVICE

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.

nbM stimulation ON for 3 months (GPi also on)

stimulation OFF DEVICE

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.

nbM stimulation OFF for 3 months (GPi is on)

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 -

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Joseph's Hospital and Medical Center, Phoenix: lead
• Barrow Neurological Foundation: collaborator

Study Sites (1)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85205-6118, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Francisco A Ponce, MD

  Barrow Brain and Spine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2016
• First Posted: October 5, 2016
• Study Start: September 1, 2016
• Primary Completion: April 15, 2021
• Study Completion: April 15, 2021
• Last Updated: September 21, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)