Cerebral Small Vessel DiseaseNCT07891650
Personalized Intermittent Theta Burst Stimulation for Cognitive Impairment Related to Cerebral Small Vessel Disease
A study testing Active Personalized Intermittent Theta Burst Stimulation in people with Cerebral Small Vessel Disease and Vascular Cognitive Impairment, run by Xuanwu Hospital, Beijing at 3 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 85 years
- Conditions the study is for
- Cerebral Small Vessel Disease, Vascular Cognitive Impairment
- What is being tested?
- Active Personalized Intermittent Theta Burst Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 3 sitesChina
- Study dates
- Oct 2026to Dec 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, 100050+
Yongbo Zhang, MD, PhD, +86 13552909549, ybzhangcn@sina.com
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, 100053
Aonan Li, MD, +86 13661339557, liaonan8696@126.com
Yi Tang, MD, PhD
Beijing Geriatric Hospital
Beijing, Beijing Municipality, 100095
Jihui Lv, MD, +86 13520094838, lvjihui@139.com
About this study
Official title: Personalized Intermittent Theta Burst Stimulation for Cognitive Impairment Related to Cerebral Small Vessel Disease: A Randomized, Double-Blind, Sham-Controlled Clinical Trial
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.
- Being tested
- Active Personalized Intermittent Theta Burst Stimulation, Sham Personalized Intermittent Theta Burst Stimulation
- Keywords
- Transcranial Magnetic Stimulation, Intermittent Theta Burst Stimulation, Neuronavigation, Dorsolateral Prefrontal Cortex, Resting-State Functional MRI
- Medical subject headings
- Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Personalized Intermittent Theta Burst StimulationDevice
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.
Sham Personalized Intermittent Theta Burst StimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Sham Personalized Intermittent Theta Burst Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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 three-month post-treatment follow-up total score minus the baseline total score. A positive change indicates improvement.
Measured: Baseline and three months after completion of the 24-week treatment period
Change From Baseline in Mini-Mental State Examination (MMSE) Total Score
The Mini-Mental State Examination (MMSE) assesses global cognitive function. Total scores range from 0 to 30, with higher scores indicating better cognitive function. Changes will be calculated separately as the total score at each post-baseline assessment minus the baseline total score. Positive changes indicate improvement.
Measured: Baseline, week 24 (end of treatment), and three months after completion of treatment
Change From Baseline in Clinical Dementia Rating (CDR) Global Score
The Clinical Dementia Rating (CDR) global score assesses the severity of cognitive and functional impairment. Possible scores are 0, 0.5, 1, 2, and 3, with higher scores indicating greater impairment. Changes will be calculated separately as the global score at each post-baseline assessment minus the baseline global score. Negative changes indicate improvement.
Measured: 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
The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is calculated by summing ratings across six cognitive and functional domains. Scores range from 0 to 18, with higher scores indicating greater impairment. Changes will be calculated separately as the score at each post-baseline assessment minus the baseline score. Negative changes indicate improvement.
Measured: Baseline, week 24 (end of treatment), and three months after completion of treatment
Change From Baseline in Activities of Daily Living (ADL) Score
Activities of daily living will be assessed using the ADL scale. Changes will be calculated separately as the score at each post-baseline assessment minus the baseline score.
Measured: Baseline, week 24 (end of treatment), and three months after completion of treatment
Change From Baseline in Auditory Verbal Learning Test (AVLT) Scores
Verbal learning and memory will be assessed using the Auditory Verbal Learning Test (AVLT). Changes will be calculated separately as each prespecified AVLT score at each post-baseline assessment minus its corresponding baseline score.
Measured: Baseline, week 24 (end of treatment), and three months after completion of treatment
Change From Baseline in Trail Making Test (TMT) Performance
Performance on the Trail Making Test (TMT) will be assessed. Changes will be calculated separately as the prespecified performance measure at each post-baseline assessment minus its corresponding baseline measure.
Measured: Baseline, week 24 (end of treatment), and three months after completion of treatment
Change From Baseline in Digit Span Test (DST) Scores
Attention and working memory will be assessed using the Digit Span Test (DST). Changes will be calculated separately as each prespecified score at each post-baseline assessment minus its corresponding baseline score.
Measured: Baseline, week 24 (end of treatment), and three months after completion of treatment
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score
Neuropsychiatric symptoms will be assessed using the Neuropsychiatric Inventory (NPI). Changes will be calculated separately as the total score at each post-baseline assessment minus the baseline total score. Higher scores indicate more severe neuropsychiatric symptoms; negative changes indicate improvement.
Measured: Baseline, week 24 (end of treatment), and three months after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionSep 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Small Vessel DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuanwu Hospital, Beijing
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Technology of the People´s Republic of China, National Natural Science Foundation of China
- Responsible party
- Sponsor
- Investigators
- Yi Tang, MD, PhD, Principal investigator, Xuanwu Hospital, Beijing
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07891650
- Sponsor's protocol ID
- 2026393001
- Status last verified
- Oct 2026
- First submitted
- 18 Oct 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is currently no plan to share individual participant data with other researchers.