Back to resultsNucleus Basalis Deep Brain Stimulation for Thinking & Memory Problems in Parkinson's.
Primary Purpose
Dementia in Parkinson's Disease
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
NBM DBS
Sponsored by
About this trial
This is an interventional treatment trial for Dementia in Parkinson's Disease
Eligibility Criteria
Inclusion Criteria:
- All patients will meet Queen Square brain bank criteria for the diagnosis of PD and will have motor fluctuations (off periods and/or L-dopa induced dyskinesias) in response to medications that are known to improve with GPi DBS, and will be appropriate candidates for GPi DBS aside from the coexistence of cognitive impairment.
Patients will be aged between 35 and 80 years.
Patients will be able to give informed consent.
Patients will meet criteria for PD dementia. Patients will have a MMSE score between 26 and lower cutoff of 21 to restrict the sample to those with mild dementia and cognitive impairment. This will be equivalent to an age and education adjusted scaled score of greater than 5 and lower than 9 (mildly impaired range) on the Mattis Dementia Rating Scale-2.
Patients will have only minimal atrophy on pre-operative brain MRI scans.
Patients will be living at home and will have a carer living with them e.g. their spouse
Able to comply with trial protocol and willing to attend clinic necessary visits
Exclusion Criteria:
- Diagnosis or suspicion of other cause for parkinsonism or dementia.
Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.
Prior intra-cerebral surgical intervention for Parkinson's disease including Deep Brain stimulation, lesional surgery, growth factor administration, gene therapy or cell transplant.
Sites / Locations
- National Hospital for Neurology & Neurosurgery
Arms of the Study
Arm 1
Arm 2
Arm Type
Sham Comparator
Active Comparator
Arm Label
NBM DBS Off
NBM DBS On
Arm Description
NBM DBS switched off
NBM DBS Switched On
Outcomes
Primary Outcome Measures
Abbreviated cognitive battery
Differences between each item of the abbreviated cognitive battery scores between patients after 3 months ON stimulation and 3 months OFF stimulation.
CVLT-II,Verbal Fluency,Simple & Choice RT (CANTAB),Digit span,Posner's covert attention test
Secondary Outcome Measures
Minimental State Examination
DRS-2
Dementia Rating Scale-2
SRM (Faces)
Short Recognition Memory for faces
WAIS-III (Letter number sequencing, Arithmetic)
Wechsler Abbreviated Scale of Intelligence
FAST
Florida Apraxia Screening test
NPI
Neuropsychiatric Inventory
BDS
Blessed Dementia Scale
HAM-D
Hamilton Depression scale
MDS UPDRS
Movement Disorders Society - Unified Parkinson's disease Rating scale
PDQ39
Parkinson's disease quality of life questionnaire
GFQ
Gait and falls questioannaire
NMS Quest
Non Motor Symptoms Questionnaire
Full Information
NCT ID
NCT01701544
First Posted
October 3, 2012
Last Updated
October 28, 2016
Sponsor
University College, London
1. Study Identification
Unique Protocol Identification Number
NCT01701544
Brief Title
Nucleus Basalis Deep Brain Stimulation for Thinking & Memory Problems in Parkinson's.
Official Title
Double Blind, Randomised, Single Centre, Crossover Pilot Trial of Bilateral Nucleus Basalis of Meynert Deep Brain Stimulation to Improve Cognitive Deficits in Patients With Parkinson's Disease.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
We will perform a pilot study to evaluate the effectiveness of human NBM DBS at improving cognitive deficits in PD patients referred and eligible for conventional DBS treatment for coexisting motor impairments. Six patients with PD with both motor fluctuations and cognitive impairments (including but not restricted to deficits in attention and working memory) will have bilateral electrodes implanted to ensure that superficial contacts lie in the conventional motor GPi target, while the deepest electrical contacts lie in the NBM- (see figure 1). We will place electrodes using our conventional image guided, stereotactic frame-based procedure currently used in patients at NHNN. Patients will be randomised into 2 groups in a crossover trial design to have 3 month periods of NBM stimulation switched on or switched off separated by a 1 month washout period, following which the patient will cross over to have the opposite condition for a further 3 months- see timeline. At the end of the crossover period, all patients will be invited for continued follow up with stimulation switched on and will have neuropsychological evaluations at 6 monthly intervals. Patients will be given the option of receiving additional conventional stimulation to the motor GPi, through the higher contacts of each electrode, at the end of the crossover period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dementia in Parkinson's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NBM DBS Off
Arm Type
Sham Comparator
Arm Description
NBM DBS switched off
Arm Title
NBM DBS On
Arm Type
Active Comparator
Arm Description
NBM DBS Switched On
Intervention Type
Device
Intervention Name(s)
NBM DBS
Intervention Description
Deep Brain Stimulation targeting the Nucleus Basalis of Meynert
Primary Outcome Measure Information:
Title
Abbreviated cognitive battery
Description
Differences between each item of the abbreviated cognitive battery scores between patients after 3 months ON stimulation and 3 months OFF stimulation.
CVLT-II,Verbal Fluency,Simple & Choice RT (CANTAB),Digit span,Posner's covert attention test
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Minimental State Examination
Time Frame
6 months
Title
DRS-2
Description
Dementia Rating Scale-2
Time Frame
6 months
Title
SRM (Faces)
Description
Short Recognition Memory for faces
Time Frame
6 months
Title
WAIS-III (Letter number sequencing, Arithmetic)
Description
Wechsler Abbreviated Scale of Intelligence
Time Frame
6 months
Title
FAST
Description
Florida Apraxia Screening test
Time Frame
6 months
Title
NPI
Description
Neuropsychiatric Inventory
Time Frame
6 months
Title
BDS
Description
Blessed Dementia Scale
Time Frame
6 months
Title
HAM-D
Description
Hamilton Depression scale
Time Frame
6 months
Title
MDS UPDRS
Description
Movement Disorders Society - Unified Parkinson's disease Rating scale
Time Frame
6 months
Title
PDQ39
Description
Parkinson's disease quality of life questionnaire
Time Frame
6 months
Title
GFQ
Description
Gait and falls questioannaire
Time Frame
6 months
Title
NMS Quest
Description
Non Motor Symptoms Questionnaire
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All patients will meet Queen Square brain bank criteria for the diagnosis of PD and will have motor fluctuations (off periods and/or L-dopa induced dyskinesias) in response to medications that are known to improve with GPi DBS, and will be appropriate candidates for GPi DBS aside from the coexistence of cognitive impairment.
Patients will be aged between 35 and 80 years.
Patients will be able to give informed consent.
Patients will meet criteria for PD dementia. Patients will have a MMSE score between 26 and lower cutoff of 21 to restrict the sample to those with mild dementia and cognitive impairment. This will be equivalent to an age and education adjusted scaled score of greater than 5 and lower than 9 (mildly impaired range) on the Mattis Dementia Rating Scale-2.
Patients will have only minimal atrophy on pre-operative brain MRI scans.
Patients will be living at home and will have a carer living with them e.g. their spouse
Able to comply with trial protocol and willing to attend clinic necessary visits
Exclusion Criteria:
Diagnosis or suspicion of other cause for parkinsonism or dementia.
Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.
Prior intra-cerebral surgical intervention for Parkinson's disease including Deep Brain stimulation, lesional surgery, growth factor administration, gene therapy or cell transplant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Foltynie, PhD
Organizational Affiliation
UCL Institute of Neurology
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Hospital for Neurology & Neurosurgery
City
London
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom
12. IPD Sharing Statement
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
derived
Learn more about this trial
Nucleus Basalis Deep Brain Stimulation for Thinking & Memory Problems in Parkinson's.
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