Cognitive Effects of Theta-burst Stimulation (TBS) in Suspected Non-Alzheimer Disease Pathophysiology (SNAP)

Not Applicable

• Conditions: Suspected Non-Alzheimer Disease Pathophysiology (SNAP)
• Interventions: Device: active and active TBS; Device: sham and active TBS

• Registration Number: NCT05440110
• Lead Sponsor: Chang Gung Memorial Hospital

Brief Summary

This is a pilot study to identify a homogeneous cohort of pathologically specific dementia with SNAP for clinical trial of brain stimulation.

Detailed Description

The investigators apply the NIA-AA criteria to identify the individuals of biomarker-defined SNAP endophenotype. This is a prospective, randomized controlled clinical trial for the first two weeks, followed by an open-label trial for the next two weeks, and combined functional neuroimaging study of 18F-FDG-PET to further explore the potential mechanisms. A total of 20 SNAP dementia patients will be recruited for consecutive two years, and be subjected to iTBS for 5 daily interventions per week for four consecutive weeks. Cognitive evaluation will be performed before and immediately after TBS intervention, and 8 weeks after TBS. Data on functional neuroimaging will be also collected before and after TBS protocol.

Study Timeline

• Study First Submitted: 2022-06-27
• Study First Submitted QC: 2022-06-27
• Study First Posted: 2022-06-30
• Study Start: 2022-10-18
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-12
• Last Update Posted: 2025-02-14
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

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

Inclusion Criteria

1. Subjects aged 50-90 year.
2. Patients meet NIA-AA research criteria for suspected non-Alzheimer disease pathophysiology (SNAP) (Petersen, Smith et al. 1999; Jack, Bennett et al. 2018), and DSM-5 criteria for major neurocognitive disorder of dementia (Regier, Narrow et al. 2013).
3. Amyloid PET should ever be performed.
4. The CDR of subjects can be 0.5-2.

Exclusion Criteria

1. Any subject has a definite diagnosis of epilepsy or history of seizure attack.
2. Current or past history of clinically significant neurological insults affecting brain structure or function like completed stroke, head injury or brain tumor. (cerebrovascular disorders, hydrocephalus and intra-cranial mass, documented by MRI; a history of traumatic brain injury or another neurological disease).
3. Any subject has clinically significant or unstable medical diseases including metabolic, renal, liver, lung or cardiovascular disorders including metabolic, renal, liver, lung or cardiovascular disorders.
4. Any subject has current alcohol or other substances abuse and/ or dependence within the recent one year, or prolonged history of major psychiatric disorder like schizophrenia, bipolar disorder, and previously prolonged substances abuse.
5. Any females who is pregnant or lactating.
6. General MRI, TMS and/or PET exclusion criteria including subjects who had received brain aneurysm surgery, or implanted pacemaker, mechanical valves, cochlear implant or other metal devices/ objects that are not MR compatible in the body.

Withdrawal criteria

1. Complications onset after intervention that affect efficacy and safety judgments.
2. New onset or progression of disease that may affect outcomes.
3. Use of other therapies or drugs during the intervention period to change cognitive functions.
4. Any subjects who are recognized as high risk of adverse effects by principle investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
active and active	active and active TBS	The patients will be subjected to TBS for 5 daily interventions per week for four consecutive weeks.
sham and active	sham and active TBS	The patients will be subjected to TBS for 5 daily interventions per week for the first two weeks, followed by an open-label trial for the next two weeks.

Primary Outcome Measures

Name	Time	Method
The changes of Mini-Mental State Examination (MMSE) total scores	baseline (T0) and immediately after 2 weeks of TBS (T2), and 4 weeks of TBS (T4), and 8-week follow-up after TBS (T12)	The changes of Mini-Mental State Examination (MMSE) total scores (score range from 0 to 30, higher values represent a better cognitive outcome)
The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores	baseline (T0) and immediately after 2 weeks of TBS (T2), and 4 weeks of TBS (T4), and 8-week follow-up after TBS (T12)	The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores (score range from 0 to 70, higher score indicates a worse cognitive outcome)

Secondary Outcome Measures

Name	Time	Method
The standard uptake values changes of FDG-PET	baseline (T0) and immediately after 2 weeks of TBS (T2), and 4 weeks of TBS (T4)	The standard uptake values (SUV) changes of cerebral glucose metabolism using 18F-FDG-PET

Trial Locations

Locations (1)

Chang Gung Memorial Hospital; 🇨🇳 Taoyuan, Guishan, Taiwan