Deep Brain Stimulation for Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

The Effect of Deep Brain Stimulation on Memory Network and Neurological Function of Alzheimer's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03959124
• Other study ID #: IRB106-68-A
• Status: Recruiting
• Phase: N/A
• Start date: April 6, 2020
• Est. completion date: September 30, 2021

Study information

• Verified date: June 2020
• Source: Buddhist Tzu Chi General Hospital
• Contact: Shin-Yuan Chen, MD.
• Phone: +886-3-8561825
• Email: william.sychen[@]msa.hinet.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 30, 2021
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Deep Brain Stimulation
• Dementia, Alzheimer Type

Intervention

Device:
• Deep brain stimulation
Brain stimulation electrodes at parameters 2.0~4.5 V;60 µs;20 Hz

Drug:
• Best medical treatment for Alzheimer's disease
Alzheimer's disease patients take medications including Exelon (Rivastigmine Tartrate), Witgen (Memantine) for at least 3 months without plan of dosage adjustment

Locations

Country	Name	City	State
Taiwan	Buddhist Tzu Chi General Hospital	Hualien City

Sponsors (2)

Lead Sponsor	Collaborator
Buddhist Tzu Chi General Hospital	Beijing Tiantan Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (6)

Canter RG, Penney J, Tsai LH. The road to restoring neural circuits for the treatment of Alzheimer's disease. Nature. 2016 Nov 10;539(7628):187-196. doi: 10.1038/nature20412. Review. — View 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. — View 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. Erratum in: Nature. 2018 Oct;562(7725):E1. — View Citation

Kuhn J, Hardenacke K, Lenartz D, Gruendler T, Ullsperger M, Bartsch C, Mai JK, Zilles K, Bauer A, Matusch A, Schulz RJ, Noreik M, Bührle CP, Maintz D, Woopen C, Häussermann P, Hellmich M, Klosterkötter J, Wiltfang J, Maarouf M, Freund HJ, Sturm V. Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia. Mol Psychiatry. 2015 Mar;20(3):353-60. doi: 10.1038/mp.2014.32. Epub 2014 May 6. — View 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. — View Citation

Kumbhare D, Palys V, Toms J, Wickramasinghe CS, Amarasinghe K, Manic M, Hughes E, Holloway KL. Nucleus Basalis of Meynert Stimulation for Dementia: Theoretical and Technical Considerations. Front Neurosci. 2018 Sep 3;12:614. doi: 10.3389/fnins.2018.00614. eCollection 2018. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)	Change from baseline in Alzheimer's Disease Assessment Scale-cognitive subscale; Total scores range from 0-70. Higher scores (= 18) indicate worse cognitive function. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities.	One year