Nucleus Basalis Deep Brain Stimulation for Thinking & Memory Problems in Parkinson's.

NCT ID: NCT01701544

Last Updated: 2016-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2015-12-31

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.

Conditions

Dementia in Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

NBM DBS Off

NBM DBS switched off

Group Type: SHAM_COMPARATOR

NBM DBS

Intervention Type: DEVICE

Deep Brain Stimulation targeting the Nucleus Basalis of Meynert

NBM DBS On

NBM DBS Switched On

Group Type: ACTIVE_COMPARATOR

NBM DBS

Intervention Type: DEVICE

Deep Brain Stimulation targeting the Nucleus Basalis of Meynert

Interventions

NBM DBS

Deep Brain Stimulation targeting the Nucleus Basalis of Meynert

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Foltynie, PhD

Role: PRINCIPAL_INVESTIGATOR

UCL Institute of Neurology

Locations

National Hospital for Neurology & Neurosurgery

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 29255885 (View on PubMed)

Other Identifiers

11/0516

Identifier Type: -

Identifier Source: org_study_id