Deep Brain Stimulation for Patients With Dementia With Lewy Bodies

Study Overview
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Brief Summary
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This trial aims to collect pilot data to explore whether bilateral deep brain stimulation (DBS) of the Nucleus Basalis of Meynert (NBM) has beneficial effects on memory and thinking impairments among individuals with Dementia with Lewy Bodies (DLB).

Detailed Description
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We will perform a pilot study to evaluate the effectiveness of human NBM DBS at improving cognitive deficits in DLB patients. Six patients with DLB with moderate cognitive impairments (including but not restricted to deficits in attention and working memory) will have bilateral DBS electrodes implanted to ensure that superficial contacts lie in the motor Globus Pallidum interna (GPi) target, while the deepest electrical contacts lie in the NBM. We will place electrodes using our conventional image-guided, stereotactic frame-based procedure. Once the surgical wounds have healed, patients will be randomised into 2 groups in a crossover trial design to have 6 week periods of NBM stimulation switched on or switched off separated by a 2 week washout period, following which the patient will cross over to have the opposite condition for a further 6 weeks. Outcome measures collected at the 6 weeks and 14 weeks timepoints will be compared according to whether each patient was ON or OFF stimulation at that timepoint. 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 if required for any coexisting Parkinsonian motor complications of DLB.

Official Title
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Double Blind, Randomised, Dual Centre, Crossover, Pilot Trial of Bilateral Nucleus Basalis of Meynert Deep Brain Stimulation to Improve Cognitive Deficits in Patients With Dementia With Lewy Bodies.

Conditions
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Dementia With Lewy Bodies

Intervention / Treatment
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* Procedure: Bilateral Nucleus Basalis Meynert DBS
* Procedure: Sham Nucleus Basalis Meynert DBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DLB Consortium Criteria for diagnosis Score between 2 & 12 on Clinician Assessment of Fluctuations scale MMSE score between 21 and 27 Appropriate Surgical candidates in terms of general health Aged between 50 & 80 Able to give Informed consent Living at home with Carer Able to comply with protocol On stable dosage of cholinesterase inhibitor Exclusion Criteria: Diagnosis of other cause for dementia Abnormality on brain imaging considered likely to compromise compliance with trial protocol. Prior intracerebral surgical intervention

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bilateral Nucleus Basalis Meynert DBS<br>6 week period of active NBM DBS | Procedure: Bilateral Nucleus Basalis Meynert DBS<br>* Low frequency stimulation applied using standard Deep brain stimualtion hardware.<br>* Other names: Active Deep Brain Stimulation;|
| Sham Comparator: Sham Nucleus Basalis Meynert DBS<br>6 week period of Sham DBS | Procedure: Sham Nucleus Basalis Meynert DBS<br>* DBS system switched off.<br>* Other names: Sham DBS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hopkins Verbal Learning test |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Verbal Fluency |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Simple & Choice Reaction time task |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Wechsler Adult Intelligence scale (WAIS IV) Digit Span |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Posner's Covert Attention test |  | Comparing ON v OFF at 6 weeks & 14 weeks according to stimulation status | 
| Clinician's Assessment of Fluctuations scale |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimental State Examination (MMSE) |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Dementia Rating Scale (DRS-2) |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Wechsler Abbreviated Scale of Intelligence (WASI) |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Short Recognition Memory |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Wechsler Adult Intelligence Scale IV -Letter, Number sequencing |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Trail Making test |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Stroop test |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Wechsler Adult Intelligence Scale IV - Symbol search |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Judgement of Line Orientation |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| North East Visual Hallucinations Interview |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Neuropsychiatric Inventory |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Florida Apraxia Screening test |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Clinical Global Impression Scale |  | Comparing ON v OFF at 6 weeks & 14 weeks according to stimulation status | 
| Hamilton Depression scale |  | Comparing ON v OFF at 6 weeks & 14 weeks according to stimulation status | 
| Hamilton Anxiety Scale |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Starkstein Apathy Rating scale |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Movement Disorders Society- Unified Parkinson's Disease Rating Scale |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Freezing of Gait- questionnaire |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Scales for outcome in Parkinson's disease (SCOPA - AUT) |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Quality of Life- Alzheimer's Disease |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Mayo Fluctuations Composite Scale |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Blessed Dementia scale |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Carer Strain Index |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status | 
| Short Form 36 |  | Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status |