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

Trial details

Who runs it

Xuanwu Hospital, Beijing

Trial code

NCT07891650

Record updated

23 October 2026

Original description

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 full original descriptionShow less

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.

Inclusion: 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.

Exclusion: A contraindication to MRI or inability to complete MRI examinations, such as metal implants or claustrophobia; 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; 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; Any other condition that, in the investigator's judgment, makes the individual unsuitable for participation; Impaired consciousness from any cause; 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.

ClinicalTrials.gov NCT07891650