Cognitive Effects and Potential Mechanisms of TBS in Subjects With MCI

Biomarker-based Prediction of Cognitive Effects and Potential Mechanisms of Theta-burst Stimulation (TBS) in Subjects With Mild Cognitive Impairment (MCI)

This study aims to examine the effects and potential mechanisms of theta-burst stimulation (TBS) on cognitive function in individuals with mild cognitive impairment (MCI).

Study Overview

• Status: Enrolling by invitation
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Device: TBS for Amyloid-positive MCI; Device: TBS for Amyloid-negative MCI

Detailed Description

The investigators apply the NIA-AA criteria to subtype different endophenotypes of biomarker-defined MCI individuals. This is a prospective, open-label clinical trial, and combined functional neuroimaging study of 18F-FDG-PET to further explore the potential mechanisms. A total of 80 MCI patients will be consecutively recruited and be subjected to iTBS for 5 daily interventions per week for two 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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan District, Taiwan
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects aged 50-90 year
2. Subjects meet Petersen's criteria for mild cognitive impairment (Petersen, Smith et al. 1999)
3. The CDR of MCI patients can be 0-0.5
4. Amyloid PET should ever be performed

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.
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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Amyloid-positive MCI; The subjects will receive active stimulation of standard intermittent TBS (iTBS) protocol.	Device: TBS for Amyloid-positive MCI; The investigators will perform standard intermittent TBS (iTBS) parameters to left DLPFC of every patient in the study. The frequency parameters of TBS are 3-pulse 50-Hz bursts, every 200 ms at 5 Hz, and the intensity is 90% of active motor threshold. A single session of iTBS contains 2 s of TBS repeated every 10 s for 20 times. In this study, The investigators will give two sessions of iTBS separated by 15 min.
Active Comparator: Amyloid-negative MCI; The subjects will receive active stimulation of standard intermittent TBS (iTBS) protocol.	Device: TBS for Amyloid-negative MCI; The investigators will perform standard intermittent TBS (iTBS) parameters to left DLPFC of every patient in the study. The frequency parameters of TBS are 3-pulse 50-Hz bursts, every 200 ms at 5 Hz, and the intensity is 90% of active motor threshold. A single session of iTBS contains 2 s of TBS repeated every 10 s for 20 times. In this study, The investigators will give two sessions of iTBS separated by 15 min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-Mental State Examination ( MMSE )	Change from baseline Mini-Mental State Examination total scores immediately after TBS intervention	Baseline and immediately after 2 weeks of TBS and 8-week follow-up after TBS
Montreal Cognitive Assessment	Change from baseline Montreal Cognitive Assessment total scores immediately after TBS intervention	Baseline and immediately after 2 weeks of TBS and 8-week follow-up after TBS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The standard uptake values changes of FDG-PET	The standard uptake values (SUV) changes of cerebral glucose metabolism using 18F-FDG-PET	Before and immediately after TBS intervention

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: KUAN YI WU, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: July 5, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Mild Cognitive Impairment; theta-burst stimulation; repetitive transcranial magnetic stimulation (rTMS)
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 202102037A3A0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No