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

Not Applicable

Not yet recruiting

• Conditions: Alzheimer's Disease-related Dementia; Alzheimer Disease; RTMS Stimulation

• Registration Number: NCT06835283
• Lead Sponsor: Baylor College of Medicine

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:

1. Is the combined brain stimulation treatment practical and well-tolerated?

2. Do preliminary results suggest that this treatment could help manage neuropsychiatric symptoms and support a larger study?

Participants will:

* 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.

Detailed Description

This study is designed to explore a new way to manage behavioral and emotional symptoms in people with Alzheimer's Disease (AD) and related dementias (ADRD). Many people with these conditions experience mood swings, apathy, or agitation, which can be difficult to treat with current medications due to limited effectiveness and side effects. This research is testing whether two types of brain stimulation, called iTBS (intermittent theta burst stimulation) and tDCS (transcranial direct current stimulation), can be combined to provide a non-invasive and potentially effective treatment for these symptoms.

Brain stimulation is already used in other areas of medicine and involves applying gentle magnetic or electrical stimulation to the brain. iTBS uses short bursts of magnetic pulses, while tDCS uses a low electrical current. Both methods are painless, safe, and do not require surgery. This study is the first to look at combining these two techniques for people with AD/ADRD, based on findings from other research that suggest the combination might have stronger effects than either method alone.

Since this is a pilot study, the focus is on understanding whether the treatment process is practical for both patients and caregivers. This includes evaluating how easy it is for participants to attend the clinic sessions, whether caregivers can successfully administer the at-home treatments, and whether the overall process is manageable for families. In addition to these practical questions, researchers will also collect preliminary data to see if the treatment helps improve behavioral symptoms and measure any changes in the brain using scans and brain activity tests.

Participants will spend one week receiving treatments in a clinic and four weeks using a portable device for at-home sessions. Researchers will closely monitor participants throughout the study to ensure safety and will follow up to see if any improvements last after the treatment ends.

The study is an important step in understanding whether this new approach has potential to help people with AD/ADRD and whether it should be studied further in larger trials. It also aims to identify how to make the treatment process as smooth and effective as possible for patients and caregivers.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-13
• Study Start: 2025-02
• Study First Submitted QC: 2025-02-17
• Last Update Submitted: 2025-02-17
• Study First Posted: 2025-02-19
• Last Update Posted: 2025-02-19
• Primary Completion: 2026-02
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

1. any contraindication for MRI
2. 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
3. current alcohol or substance use disorder determined by QuickSCID (nicotine allowed; mild cannabis and alcohol use is allowed)
4. neuropsychiatric symptoms (NPS) that are severe enough to preclude the intervention from being delivered safely and effectively, particularly agitation or aggression.

6. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Feasibility of iTBS-tDCS treatment in ADRD patients	From enrollment until the end of treatment at 5 weeks	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.
Tolerability of iTBS-tDCS treatment in ADRD patients	From enrollment until the end of treatment at 5 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Neuropsychiatric Symptoms	From enrollment until the end of treatment at 5 weeks	We will gather preliminary data on the potential effects of iTBS-tDCS on neuropsychiatric symptoms in individuals with Alzheimer's Disease and related dementias, as determined by changes in standardized neuropsychiatric symptom questionnaires pre- and post-treatment.
Caregiver burden	At baseline (week 0) and post-treatment (week 6)	We will also explore the potential impact of the treatment on caregiver burden using caregiver-reported outcomes collected before and after the intervention. The total score of caregiver burden will involve the sum of the responses to all items on the Zarit Burden Interview assessment, and these scores are rated on a Likert scale of 0-4. This total score quantifies the level of caregiver burden, as high scores will indicate greater burden. Descriptive statistics; such as mean, median, and standard deviation-will summarize the overall caregiver burden within the study sample. Other factors associated with determining caregiver burden include inferential statistical methods like multiple regression analysis or ANOVA, as these will be used to examine connections between ZBI scores and variables such as patient cognitive function, treatment compliance, and demographic factors.
Brain connectivity through MRI	At baseline visit (week 0) and post-treatment (week 6)	We can observe potential changes in brain connectivity through functional MRI scans conducted pre- and post-treatment, to inform hypotheses for future studies. The MRI will be used to obtain baseline images and neuromodulation-induced changes of brain structure as well as functional connectivity, particularly in the default mode and salience networks.