A Trial to Test Intermittent Deep Brain Stimulation of Nucleus Basalis of Meynert to Treat Alzheimers.

Official title

Cognitive Brain Aging Reversal From Deep Brain Stimulation for Alzheimer's Dementia: a Clinical Trial.

Overview

The purpose of this study is to test a new procedure to treat Alzheimer's disease. The procedure is called intermittent Deep Brain Stimulation (DBS) of the nucleus basalis of Meynert. There will be up to six participants enrolled at Wellstar MCG Memory Clinic. There will be another six participants similarly enrolled to act as a control group that does not receive DBS. This second group will document the course of progression of Alzheimer's disease under the normal standard of care. The main goal of the study is to determine if DBS can sustain or improve cognition in Alzheimer's disease for at least two years. Participant data, with identifying information removed, may be shared with online repositories for comparison with trials with similar subjects.

Interventions

• Device Intermittent deep brain stimulation of the nucleus basalis of Meynert
  Subjects will receive intermittent deep brain stimulation of the nucleus basalis of Meynert for 50 minutes each day.

Primary outcome measures

• Dementia Rating Scales [Time frame: Two years after intervention onset]
• Alzheimer's Disease Assessment Scale, Cognitive Subscale [Time frame: Two years of intervention]

Secondary outcome measures (4)

• PET scans for beta amyloid [Time frame: Two years after study onset.]
• Anxiety scales [Time frame: Two years of intervention]
• Beta amyloid PET imaging, Centiloid scale. [Time frame: Two years of intervention]
• PHQ-9 questionaire [Time frame: Two years of intervention]

Eligibility criteria

Inclusion criteria

• Age:65 minimum

• Age:85 maximum
• Probable, early-stage Alzheimer's Disease, as defined by NIA-AA 2018 criteria and positive PET for beta amyloid,
• no Lewy-Body-dementia or other form of dementia
• Clinical Dementia Rating (CDR) global score of 0.5-1.0 with a CBR-sb score from 2 to 6.
• MMSE ≥ 21
• stable psychopharmacological medication equivalent to 10 mg/day donepezil or less for at least 60 days
• valid informed consent
• an available caregiver willing to participate
• subject is living at home and likely to remain at home for the study duration
• Geriatric Depression Scale of 5 or less
• Columbia Suicide Severity Rating Scale "No" on questions 3 through 5
• Neuropsychiatric Inventory (NPI-Q) under 2 on 'Delusions', 'Hallucinations' or 'Agitation/Aggression' subscales

Exclusion criteria

• • clinical co-morbidity interfering with study (e.g. head trauma requiring medical treatment in the 2 years prior, brain tumor, subdural hematoma, or other clinically significant space-occupying lesion on brain CT or MRI), or other implant precluding high field MRI scans.

• current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit, or past medical history prior suicidal attempts or suicidal crises
• Another concurrent CNS condition (ie, stroke, Parkinson's disease, Lewy-Body dementia or other form of dementia, other evidence of significant structural brain pathology).
• Medical history of seizure disorder including epilepsy
• Terminal illness associated with expected survival of <30 months
• Subjects with one of these other forms of dementia in the DSM-5 heading of Neurocognitive Disorders: Lewy body disease, Frontotemporal lobar degeneration, Vascular disease, Traumatic brain injury, HIV infection, Prion disease, Parkinson's disease, Huntington's disease, or due to multiple etiologies
• Subjects with unstable medical and neurological conditions at the discretion of the Principle Investigator

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Wellstar MCG Hospital, Neurology Memory Clinic — Augusta

Publications

• Sasikumar S, Cohn M, Youm A, Duncan K, Boogers A, Strafella AP, Blake DT, Fasano A. Rethinking NBM DBS: Intermittent stimulation improves sustained attention in Parkinson's disease. Brain Stimul. 2023 Nov-Dec;16(6):1643-1645. doi: 10.1016/j.brs.2023.10.014. Epub 2023 Nov 5. No abstract available. PMID 37935282
• Kumro J, Tripathi A, Lei Y, Sword J, Callahan P, Terry A, Lu XY, Kirov SA, Pillai A, Blake DT. Chronic basal forebrain activation improves spatial memory, boosts neurotrophin receptor expression, and lowers BACE1 and Abeta42 levels in the cerebral cortex in mice. Cereb Cortex. 2023 Jun 8;33(12):7627-7641. doi: 10.1093/cercor/bhad066. PMID 36939283
• Pennington KR, Debs L, Chung S, Bava J, Garin CM, Vale FL, Bick SK, Englot DJ, Terry AV Jr, Constantinidis C, Blake DT. Basal forebrain activation improves working memory in senescent monkeys. Brain Stimul. 2025 Mar-Apr;18(2):185-194. doi: 10.1016/j.brs.2025.02.002. Epub 2025 Feb 7. PMID 39924100
• Liu R, Crawford J, Callahan PM, Terry AV Jr, Constantinidis C, Blake DT. Intermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys. Curr Biol. 2017 Sep 11;27(17):2640-2646.e4. doi: 10.1016/j.cub.2017.07.021. Epub 2017 Aug 17. PMID 28823679

Identifiers

NCT: NCT07218081 · 2300118-2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗