Clinical trial NCT01701544: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Dementia in Parkinson's Disease
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2012-10-05
Enrollment: 6
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Abbreviated cognitive battery
timeFrame: 6 months
Secondary outcomes:
measure: Minimental State Examination
timeFrame: 6 months
measure: DRS-2
timeFrame: 6 months
measure: SRM (Faces)
timeFrame: 6 months
measure: WAIS-III (Letter number sequencing, Arithmetic)
timeFrame: 6 months
measure: FAST
timeFrame: 6 months
measure: NPI
timeFrame: 6 months
measure: BDS
timeFrame: 6 months
measure: HAM-D
timeFrame: 6 months
measure: MDS UPDRS
timeFrame: 6 months
measure: PDQ39
timeFrame: 6 months
measure: GFQ
timeFrame: 6 months
measure: NMS Quest
timeFrame: 6 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: National Hospital for Neurology & Neurosurgery
Study officials:
affiliation: UCL Institute of Neurology
name: Thomas Foltynie, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.