Clinical trial NCT03959124: Deep Brain Stimulation for Alzheimer's Disease
Official title: The Effect of Deep Brain Stimulation on Memory Network and Neurological Function of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Alzheimer Disease
Dementia, Alzheimer Type
Deep Brain Stimulation
Keywords: magnetic resonance image
Lead sponsor: Buddhist Tzu Chi General Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Tiantan Hospital
First posted: 2019-05-22
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and preliminary efficacy of nucleus basalis of Meynert (NBM)-DBS in Alzheimer's disease (AD) is proved in a recent phase 1 clinical trial, yet, the mechanism still unknown.

Objective: 1. To compare the brain structure and functional circuits between a) AD patients with optimal drug treatment (ODT) plus NBM-DBS, b) AD with ODT and c) normal age-and sex-matched control. 2. To evaluate the clinical effectiveness of NBM-DBS in AD patients 60-75 year-old. 3. To evaluate the abnormal functional circuitry response to acute and chronic NBM-DBS in AD.

Methods: A total of 30 subjects (10 subjects of AD with ODT plus NBM-DBS; 10 subjects of AD with ODT and 10 subjects of normal age-and sex-matched subjects) will be enrolled in this prospective, with normal control, Phase II study. Study tools will include clinical rating batteries, structure and functional imaging of magnetic resonance (MR) and positron emission tomography (PET), and electroencephalogram (EEG).

Expected Results: NBM-DBS will be proved to be an safe and effective treatment modality in AD patients 60-75 year-old. Through multi-modal images and EEG analysis, the possible action mechanisms of NBM-DBS on memory circuit will be discussed. The study results may shed a light on this helpless neurodegenerative disease of dementia.


Eligibility criteria: Inclusion Criteria:

For groups (AD with/ without DBS)

1. Confirmed Alzheimer's dementia diagnosis
2. Regular medications taking for at least 3 months
3. Clinical Dementia Rating: 0.5 - 2
4. Mini Mental Status Examination: ≦ 26
5. Amyloid PET: positive
6. Informed consent signed by patients or families

For normal control group

1. No cognitive impairment (Mini Mental Status Examination)
2. Amyloid PET: negative
3. Informed consent signed by patients and families

Exclusion Criteria:

For groups (AD with/ without DBS)

1. Structural lesions identified by Magnetic resonance imaging (ex: stroke, brain surgery)
2. Other neurodegenerative/ neuropsychiatric diseases
3. Systemic medical diseases with cognitive impairment (ex: anemia, thyroid disease)
4. Can't have regular follow-up visit

For normal control group

1. Structural lesions identified by Magnetic resonance imaging (ex: stroke, brain surgery)
2. Dementia/ neurodegenerative/ neuropsychiatric diseases
3. Systemic medical diseases with cognitive impairment (ex: anemia, thyroid disease)
4. Can't have regular follow-up visit

Primary outcomes:
measure: Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
timeFrame: One year
Secondary outcomes:
Other outcomes:
Locations:
city: Hualien City
country: Taiwan
facility: Buddhist Tzu Chi General Hospital
Study officials:
affiliation: Buddhist Tzu Chi General Hospital
name: Shin-Yuan Chen, MD.
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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citation: Kuhn J, Hardenacke K, Shubina E, Lenartz D, Visser-Vandewalle V, Zilles K, Sturm V, Freund HJ. Deep Brain Stimulation of the Nucleus Basalis of Meynert in Early Stage of Alzheimer's Dementia. Brain Stimul. 2015 Jul-Aug;8(4):838-9. doi: 10.1016/j.brs.2015.04.002. Epub 2015 Apr 18. No abstract available.
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citation: Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587.