Personalized Intermittent Theta Burst Stimulation for Cognitive Impairment Related to Cerebral Small Vessel Disease

NCT07891650 | Not Yet Recruiting

• 1 other identifier: 2026393001
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate whether personalized intermittent theta burst stimulation (iTBS), a form of noninvasive transcranial magnetic stimulation, can safely improve cognitive function in people with cognitive impairment related to cerebral small vessel disease. The study will enroll 160 adults aged 45-85 years with mild cognitive impairment or mild vascular dementia related to cerebral small vessel disease. Participants will be randomly assigned in equal numbers to receive active iTBS or sham stimulation. Brain magnetic resonance imaging (MRI) will be used to identify an individualized stimulation target in the left prefrontal cortex. Sham stimulation will mimic the treatment experience without delivering effective magnetic stimulation. Participants and outcome assessors will not know which treatment participants receive. Treatment will last 24 weeks. Participants will receive four stimulation sessions per day for five consecutive days during the first week, followed by four sessions on one day each week during weeks 2-24. Cognitive assessments will be performed before treatment, during treatment, at the end of treatment, and three months after treatment ends. The main outcome is the change in Montreal Cognitive Assessment (MoCA) score from baseline to week 24. Brain MRI, electroencephalography (EEG), and adverse event monitoring will be used to examine changes in brain function and treatment safety.

Conditions

Cerebral Small Vessel Disease; Vascular Cognitive Impairment

Keywords

Transcranial Magnetic Stimulation; Intermittent Theta Burst Stimulation; Neuronavigation; Dorsolateral Prefrontal Cortex; Resting-State Functional MRI

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Week 24

  The Montreal Cognitive Assessment (MoCA) assesses global cognitive function. Total scores range from 0 to 30, with higher scores indicating better cognitive function. Change will be calculated as the week 24 total score minus the baseline total score. A positive change indicates improvement.

  Baseline and week 24 (end of treatment)

Secondary Outcomes (9)

• Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Three Months After Treatment

  Baseline and three months after completion of the 24-week treatment period

• Change From Baseline in Mini-Mental State Examination (MMSE) Total Score

  Baseline, week 24 (end of treatment), and three months after completion of treatment

• Change From Baseline in Clinical Dementia Rating (CDR) Global Score

  Baseline, week 24 (end of treatment), and three months after completion of treatment

• Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score

  Baseline, week 24 (end of treatment), and three months after completion of treatment

• Change From Baseline in Activities of Daily Living (ADL) Score

  Baseline, week 24 (end of treatment), and three months after completion of treatment

Other Outcomes (2)

• Change From Baseline in Resting-State and Task-Related Electroencephalographic Measures

  Baseline, week 1 (end of induction), week 24 (end of treatment), and three months after completion of treatment

• Change From Baseline in Multimodal Magnetic Resonance Imaging Measures

  Baseline, week 24 (end of treatment), and three months after completion of treatment

Study Arms (2)

Active Personalized Intermittent Theta Burst Stimulation

EXPERIMENTAL

Participants will receive active personalized intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex, with the target individualized using resting-state functional MRI and neuronavigation. Treatment will last 24 weeks: four sessions per day for five consecutive days in week 1, followed by four sessions on one treatment day each week during weeks 2-24. Each session will deliver 1,800 pulses at 80-100% of the resting motor threshold, adjusted according to tolerability, with 50-60 minutes between sessions.

Device: Active Personalized Intermittent Theta Burst Stimulation

Sham Personalized Intermittent Theta Burst Stimulation

SHAM COMPARATOR

Participants will receive sham stimulation at the individualized left dorsolateral prefrontal cortex target using a dedicated sham coil or sham mode. Sham stimulation will mimic the sounds, vibration, and procedures of active treatment without delivering effective magnetic stimulation. The schedule will match the active group: four sessions per day for five consecutive days in week 1, followed by four sessions on one treatment day each week during weeks 2-24, with 50-60 minutes between sessions.

Device: Sham Personalized Intermittent Theta Burst Stimulation

Interventions

Active Personalized Intermittent Theta Burst Stimulation DEVICE

Active intermittent theta burst stimulation (iTBS) will target the individualized left dorsolateral prefrontal cortex site selected using resting-state functional MRI connectivity with the frontoparietal network and neuronavigation. Intensity will be 80-100% of the resting motor threshold, adjusted for tolerability. Each session will deliver 1,800 pulses using three-pulse bursts at 50 Hz, repeated at 5 Hz, with 2-second stimulation trains and 8-second intervals. Four sessions will be administered per treatment day, with 50-60 minutes between sessions. Treatment will occur on five consecutive days in week 1 and on one day per week during weeks 2-24, totaling 112 sessions.

Active Personalized Intermittent Theta Burst Stimulation

Sham Personalized Intermittent Theta Burst Stimulation DEVICE

Sham stimulation will target the same individualized left dorsolateral prefrontal cortex site using a dedicated sham coil or sham mode. It will mimic the sounds, vibration, and procedures of active treatment without delivering effective magnetic stimulation. The treatment schedule will match the active intervention: four sessions per treatment day, with 50-60 minutes between sessions, on five consecutive days in week 1 and on one day per week during weeks 2-24, totaling 112 sessions.

Sham Personalized Intermittent Theta Burst Stimulation

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 45-85 years, of either sex.
• Cognitive decline in memory or another cognitive domain, reported by the participant or an informant, lasting at least three months; brain MRI evidence of cerebral small vessel disease (CSVD); and a diagnosis of CSVD-related vascular cognitive impairment.
• Vascular mild cognitive impairment or mild vascular dementia. Vascular mild cognitive impairment is defined as impairment in one or more cognitive domains with largely preserved independence in daily activities. Mild vascular dementia is defined as cognitive impairment that mildly affects instrumental activities of daily living or activities of daily living, while the participant remains able to complete study assessments and treatment.
• Neuropsychological evidence of cognitive impairment: Mini-Mental State Examination (MMSE) score ≥18 and \<28, with a lower threshold of ≥16 for participants with primary school education; Clinical Dementia Rating (CDR) score of 0.5 or 1; or cognitive impairment determined after adjustment for educational attainment.
• Relatively stable overall functional status, with a modified Rankin Scale (mRS) score ≤2.
• Brain MRI findings consistent with CSVD, meeting at least one of the following:
• Multiple supratentorial small subcortical infarcts, with or without white matter lesions.
• Moderate-to-severe white matter hyperintensities, with a Fazekas score ≥2, with or without lacunar infarcts.
• Other CSVD-related imaging findings, such as cerebral microbleeds or enlarged perivascular spaces.
• No acute cerebrovascular event, including acute cerebral infarction, intracerebral hemorrhage, or transient ischemic attack, within the preceding three months.
• No or only mild hippocampal/medial temporal lobe atrophy, with a medial temporal atrophy (MTA) score of 0-1.
• Written informed consent voluntarily provided by the participant or their legally authorized representative.

You may not qualify if:

• Cognitive impairment primarily explained by another disease, including Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, Parkinson's disease-related cognitive impairment, normal pressure hydrocephalus, brain tumor, demyelinating disease, encephalitis, epilepsy, or severe traumatic brain injury.
• Large cortical infarction, watershed infarction, strategic infarction, intracerebral hemorrhage, hydrocephalus, or another brain lesion sufficient to explain the cognitive impairment.
• Impaired consciousness from any cause.
• Severe depression, a psychotic disorder, or another severe psychiatric disorder.
• Severe systemic disease or a metabolic abnormality that may cause cognitive impairment, such as severe hepatic or renal dysfunction, thyroid dysfunction, vitamin B12 or folate deficiency, severe anemia, or active infection.
• A history of alcohol or drug abuse or dependence.
• A contraindication to intermittent theta burst stimulation (iTBS), including a history of seizures, a first-degree relative with epilepsy, intracranial metal implants, a cardiac pacemaker, a cochlear implant, a deep brain stimulator, a vagus nerve stimulator, or another implanted electronic or metallic medical device.
• A contraindication to MRI or inability to complete MRI examinations, such as metal implants or claustrophobia.
• Transcranial magnetic stimulation or another neuromodulation treatment within the preceding three months.
• Pregnancy, breastfeeding, or plans to become pregnant during the study.
• Current participation in another interventional clinical study.
• Any other condition that, in the investigator's judgment, makes the individual unsuitable for participation.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead
• Ministry of Science and Technology of the People´s Republic of China: collaborator
• National Natural Science Foundation of China: collaborator

Study Sites (3)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050+, China

Location

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, 100053, China

Location

Beijing Geriatric Hospital

Beijing, Beijing Municipality, 100095, China

Location

MeSH Terms

Conditions

Cerebral Small Vessel Diseases

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Yi Tang, MD, PhD

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aonan Li

CONTACT

+86 13661339557; liaonan8696@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants, clinical outcome assessors, data collection personnel, and statistical analysts will remain blinded to treatment assignment. Stimulation operators will know the assigned treatment mode but will not participate in efficacy assessments or statistical analyses. Sham stimulation will mimic the sounds, vibration, and procedures of active treatment without delivering effective magnetic stimulation. Participants will be asked to guess their treatment assignment at the end of treatment to assess masking.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, randomized, sham-controlled, parallel-group study. A total of 160 participants will be assigned in a 1:1 ratio to active personalized intermittent theta burst stimulation (iTBS) or sham stimulation, with 80 participants per group. Stratified block randomization will account for white matter hyperintensity burden and cognitive impairment severity. Both groups will follow the same 24-week treatment schedule, followed by a three-month post-treatment follow-up.

Study Record Dates

• First Submitted: October 18, 2026
• First Posted: October 23, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 23, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)