Clinical trial NCT02263937: Deep Brain Stimulation for Patients With Dementia With Lewy Bodies
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dementia With Lewy Bodies
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2014-10-13
Enrollment: 6
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Hopkins Verbal Learning test
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Verbal Fluency
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Simple & Choice Reaction time task
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Wechsler Adult Intelligence scale (WAIS IV) Digit Span
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Posner's Covert Attention test
timeFrame: Comparing ON v OFF at 6 weeks & 14 weeks according to stimulation status
measure: Clinician's Assessment of Fluctuations scale
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
Secondary outcomes:
measure: Minimental State Examination (MMSE)
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Dementia Rating Scale (DRS-2)
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Wechsler Abbreviated Scale of Intelligence (WASI)
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Short Recognition Memory
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Wechsler Adult Intelligence Scale IV -Letter, Number sequencing
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Trail Making test
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Stroop test
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Wechsler Adult Intelligence Scale IV - Symbol search
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Judgement of Line Orientation
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: North East Visual Hallucinations Interview
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Neuropsychiatric Inventory
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Florida Apraxia Screening test
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Clinical Global Impression Scale
timeFrame: Comparing ON v OFF at 6 weeks & 14 weeks according to stimulation status
measure: Hamilton Depression scale
timeFrame: Comparing ON v OFF at 6 weeks & 14 weeks according to stimulation status
measure: Hamilton Anxiety Scale
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Starkstein Apathy Rating scale
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Movement Disorders Society- Unified Parkinson's Disease Rating Scale
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Freezing of Gait- questionnaire
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Scales for outcome in Parkinson's disease (SCOPA - AUT)
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Quality of Life- Alzheimer's Disease
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Mayo Fluctuations Composite Scale
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Blessed Dementia scale
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Carer Strain Index
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
measure: Short Form 36
timeFrame: Comparing ON v OFF stimulation at 6 weeks & 14 weeks according to stimulation status
Other outcomes:
measure: Adverse Events
timeFrame: Throughout trial period
Locations:
city: London
country: United Kingdom
facility: UCL Institute of Neurology
city: Newcastle
country: United Kingdom
facility: University of Newcastle
Study officials:
affiliation: UCL Institute of Neurology
name: Thomas Foltynie, MB BS MRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gratwicke J, Zrinzo L, Kahan J, Peters A, Brechany U, McNichol A, Beigi M, Akram H, Hyam J, Oswal A, Day B, Mancini L, Thornton J, Yousry T, Crutch SJ, Taylor JP, McKeith I, Rochester L, Schott JM, Limousin P, Burn D, Rossor MN, Hariz M, Jahanshahi M, Foltynie T. Bilateral nucleus basalis of Meynert deep brain stimulation for dementia with Lewy bodies: A randomised clinical trial. Brain Stimul. 2020 Jul-Aug;13(4):1031-1039. doi: 10.1016/j.brs.2020.04.010. Epub 2020 Apr 22.