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

NCT07218081 | Recruiting Phase 1 DMC FDA Device

• 1 other identifier: 2300118-2
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Dementia (AD)

Keywords

deep brain stimulation; alzheimer's; nucleus basalis of Meynert

Outcome Measures

Primary Outcomes (2)

• Dementia Rating Scales

  Subjects will be evaluated using the Clinical Dementia Rating Sum of Boxes scale. The investigators seeks for half of the intervention arm participants to have better (lower) or equal scale scores two years after intervention onset than they had at onset. This scale ranges from 0 to 18, and subjects will score from 2 to 6 at study entry.

  Two years after intervention onset

• Alzheimer's Disease Assessment Scale, Cognitive Subscale

  The investigators seeks for scores on the Alzheimer's Disease Assessment Scale, Cognitive Subscale, to be equal or lower in half of the participants two years after the intervention begins compared to their value at study onset. This scale ranges from 0 to 85, and subjects at onset will likely have scores between 13 and 30.

  Two years of intervention

Secondary Outcomes (4)

• PET scans for beta amyloid

  Two years after study onset.

• Anxiety scales

  Two years of intervention

• Beta amyloid PET imaging, Centiloid scale.

  Two years of intervention

• PHQ-9 questionaire

  Two years of intervention

Study Arms (2)

Intermittent deep brain stimulation of the nucleus basalis of Meynert

EXPERIMENTAL

Subjects will receive intermittent deep brain stimulation of the nucleus basalis of Meynert for 50 minutes each day. Assessments will be performed at onset, after four weeks of intervention, and each six months through two years.

Device: Intermittent deep brain stimulation of the nucleus basalis of Meynert

Control group

NO INTERVENTION

Subjects will have matching eligility criteria as those in the experimental arm, but will receive no intervention. Assessments will be performed at study onset, and each six months through two years after onset.

Interventions

Intermittent deep brain stimulation of the nucleus basalis of Meynert DEVICE

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

Intermittent deep brain stimulation of the nucleus basalis of Meynert

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Augusta University: lead

Study Sites (1)

Wellstar MCG Hospital, Neurology Memory Clinic

Augusta, Georgia, 30912, United States

RECRUITING

Related Publications (4)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

David T Blake, PhD

CONTACT

415-515-2659; dblake@augusta.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor David T. Blake

Model Details: Six subjects will receive open label intermittent deep brain stimulation of the nucleus basalis of Meynert for 50 minutes daily. Six control subjects will document expected progression under normal standard of care.

Study Record Dates

• First Submitted: September 29, 2025
• First Posted: October 20, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be shared upon publication and will be available indefinitely.
• Access Criteria: Access will be open.

Locations

US (1)