Novel Brain Stimulation Treatment for Neuropsychiatric Symptoms in Alzheimer's Disease

NCT06835283 | Recruiting FDA Device

• 1 other identifier: H-56426
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this pilot study is to test a combination of two non-invasive brain stimulation methods, called iTBS (intermittent theta burst stimulation) and tDCS (transcranial direct current stimulation), in people with Alzheimer's Disease (AD) and related dementias (ADRD). This study will also explore whether the combined treatment shows promise for reducing neuropsychiatric symptoms like mood swings, apathy, and agitation, and will evaluate the impact of the treatment on caregivers. The main questions the study aims to answer are:

• Attend nine in-person visits over three months.
• Complete one week of in-clinic brain stimulation sessions (iTBS) followed by four weeks of daily at-home brain stimulation sessions (tDCS).
• Take part in brain scans, questionnaires, and brain activity tests before and after the treatment. This pilot study is a first step to assess whether this combined treatment approach is practical and whether it has potential to improve symptoms, laying the groundwork for larger studies in the future.

Conditions

Alzheimer&Amp;#39;s Disease-related Dementia; Alzheimer Disease; rTMS Stimulation

Keywords

Alzheimer's Disease; tDCS; iTBS; brain stimulation; mood swings

Outcome Measures

Primary Outcomes (2)

• Feasibility of iTBS-tDCS treatment in ADRD patients

  The feasibility of providing sequential iTBS-tDCS treatment to ADRD patients with neuropsychiatric symptoms is a primary focus. Feasibility will be assessed mainly through rates of by recruitment, retention and adherence. Recruitment rate is the number of enrolled patients divided by the total number of patients who initially approached the study or had interest in it. Retention rate is the percentage of patients who complete the entire study out of the initial enrolled participants, and then adherence rate is the number of completed iTBS and tDCS sessions divided by the total prescribed treatment sessions. Since feasibility is being evaluated as the primary aim instead of efficacy, there is no randomization or probability of group assignment. Each and every subject will undergo the same treatment stimulation process, as they will all have 1 week of in-clinic iTBS sessions and then four weeks of at-home tDCS sessions.

  From enrollment until the end of treatment at 5 weeks

• Tolerability of iTBS-tDCS treatment in ADRD patients

  The tolerability of providing sequential iTBS-tDCS treatment to ADRD patients with neuropsychiatric symptoms. Tolerability will be evaluated based on the frequency and severity of adverse events reported during the intervention period. These findings will inform the design and implementation of a larger clinical trial.

  From enrollment until the end of treatment at 5 weeks

Secondary Outcomes (3)

• Neuropsychiatric Symptoms

  From enrollment until the end of treatment at 5 weeks

• Caregiver burden

  At baseline (week 0) and post-treatment (week 6)

• Brain connectivity through MRI

  At baseline visit (week 0) and post-treatment (week 6)

Study Arms (1)

Brain Stimulation

OTHER

Participants will receive a combination of two non-invasive brain stimulation treatments. During the first week, iTBS sessions will be administered in-clinic for five consecutive days, using magnetic pulses to target brain areas associated with neuropsychiatric symptoms. This is followed by four weeks of daily, self-administered tDCS at home, delivering a low electrical current to modulate brain activity. Participants will complete brain scans and questionnaires at various points to evaluate changes in the brain and symptom severity.

Device: Brain Stimulation

Interventions

Brain Stimulation DEVICE

This intervention is distinct because it combines two non-invasive brain stimulation techniques, intermittent theta burst stimulation (iTBS) and transcranial direct current stimulation (tDCS), in a sequential manner. Unlike studies that evaluate these techniques individually, this study explores their combined and complementary effects, with iTBS priming the brain to enhance the subsequent impact of tDCS. The sequential design leverages different mechanisms of action: iTBS delivers magnetic pulses to targeted brain areas to modulate neural activity, while tDCS applies a low electrical current for sustained modulation. This approach specifically targets neuropsychiatric symptoms (e.g., mood swings, apathy, and agitation) in individuals with Alzheimer's Disease and related dementias (ADRD), a population often underserved by traditional interventions. The study also evaluates the feasibility of at-home tDCS administration, making it unique in combining clinical and caregiver-managed treat

Brain Stimulation

Eligibility Criteria

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

You may qualify if:

• veteran between the ages of 60 to 85
• clinical diagnosis of mild to moderate Alzheimer's disease or related dementia
• clinically significant neuropsychiatric symptoms (NPS) evidenced by a score ≥ 2 in at least one domain of the Neuropsychiatric Inventory Questionnaire
• mild to moderate cognitive impairment demonstrated by a Mini-Mental State Examination (MMSE) score of 15-23
• have a caregiver who is able and willing to escort the patient to/from clinic visits, answer questionnaires, and assist in the implementation of treatment sessions at home
• if taking psychotropic medications, demonstrate stability for at least 4 weeks of treatment

You may not qualify if:

• any contraindication for MRI
• any contraindication for iTBS/tDCS including but not limited to seizure disorder, severe cardiovascular disease, history of brain surgery, or stroke involving the cerebral cortex near area of stimulation
• current alcohol or substance use disorder determined by QuickSCID (nicotine allowed; mild cannabis and alcohol use is allowed)
• neuropsychiatric symptoms (NPS) that are severe enough to preclude the intervention from being delivered safely and effectively, particularly agitation or aggression.
• \) any unstable coexisting medical condition that in the opinion of the principal investigator(s) interferes with the treatment protocol or increase the likelihood of adverse events.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Michael E. DeBakey VA Medical Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Ahn H, Sorkpor S, Miao H, Zhong C, Jorge R, Park L, Abdi S, Cho RY. Home-based self-administered transcranial direct current stimulation in older adults with knee osteoarthritis pain: An open-label study. J Clin Neurosci. 2019 Aug;66:61-65. doi: 10.1016/j.jocn.2019.05.023. Epub 2019 May 29.

  PMID: 31153751 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Central Study Contacts

Lane Witkowski Research Coordinator

CONTACT

206-419-1261; Lane.Witkowski@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Model Details: This study investigates a novel approach to managing neuropsychiatric symptoms in Alzheimer's Disease and related dementias using a sequential brain stimulation model. The study combines two techniques: intermittent theta burst stimulation (iTBS) and transcranial direct current stimulation (tDCS). The process begins with in-clinic iTBS sessions to "prime" the brain, potentially enhancing its plasticity and receptiveness to subsequent treatments. This is followed by four weeks of at-home tDCS sessions, administered with caregiver assistance. The sequential use of these treatment methods is based on research suggesting that combining techniques may amplify therapeutic effects. The study aims to evaluate both the feasibility of this approach and its potential effects on symptoms and brain function, providing insights for future larger clinical trials.

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: February 19, 2025
• Study Start: August 11, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: October 22, 2025

Record last verified: 2025-08

Locations

US (1)