Intermittent theta-burst brain stimulation to improve thinking in people with small vessel brain disease

Intermittent Theta Burst Stimulation on Cognitive Impairment of Cerebral Small Vessel Disease

This trial will try intermittent theta-burst stimulation (a form of noninvasive brain stimulation) to see if it helps cognition in people aged 45–80 with vascular cognitive impairment from cerebral small vessel disease.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 58 (estimated)
• Ages: 45 Years to 80 Years
• Sex: All
• Sponsor: Beijing Tiantan Hospital (Academic / other)
• Locations: 1 site (Beijing)
• Trial ID: NCT06579664 on ClinicalTrials.gov

What this trial studies

This is a randomized, single-center, double-blind, sham-controlled parallel trial enrolling about 58 patients with imaging-confirmed cerebral small vessel disease and mild vascular cognitive impairment. Participants receive either active intermittent theta-burst stimulation (iTBS) or sham iTBS guided by Personalized Brain Function Sector mapping derived from resting-state fMRI. The study measures safety, feasibility, and changes in cognitive performance (MoCA range for eligibility was 10–22) after a course of treatments. The trial excludes very recent stroke and other standard contraindications to TMS or MRI.

Who should consider this trial

Good fit: Ideal candidates are people aged 45–80 with imaging evidence of cerebral small vessel disease, mild vascular cognitive impairment (MoCA 10–22), independent daily function (mRS ≤2), and stable medications for at least four weeks.

Not a fit: Patients with more advanced dementia, recent stroke (within 30 days), significant disability (mRS >2), contraindications to MRI or TMS, or cognitive impairment from nonvascular causes are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, iTBS guided by individualized brain-network mapping could improve memory and other cognitive functions and offer a noninvasive treatment option for vascular cognitive impairment from small vessel disease.

How similar studies have performed: Repetitive TMS and intermittent TBS have shown benefits in depression, Parkinson's disease, and some post-stroke cognitive work, but using iTBS guided by personalized resting-state fMRI specifically for CSVD-related cognitive impairment is a novel and largely untested approach.

Eligibility criteria

Inclusion Criteria：

1. Age 45-80 years old, with no limitation on sex.
2. Clinical evidence of CVSD as evidenced by one or more of:

   * White matter hyperintensity with Fazekas score ≥2
   * a lacunar stroke syndrome (e.g. pure motor stroke, pure sensory stroke, sensorimotor stroke, ataxic hemiparesis, or clumsy hand dysarthria syndrome) with a corresponding acute lacunar infarct on diffusion weighted imaging (DWl) for cases imaged (clinically) within 3 weeks of stroke or anatomically compatible lacunar infarct on fluid attenuated inversion recovery (FLAIR)/T1 MRI for cases imaged later after stroke (diameter≤1.5cm).
3. Independence of daily life (modified Rankin Scale score ≤2).
4. Mild vascular cognitive impairment (memory and/or other cognitive domain abnormalities lasting for at least 3 months) with a MoCA score of 10-22.
5. Routine, consistent medication for 4 weeks or more.

Exclusion Criteria:

1. History of stroke within previous 30 days, including cerebral infarction (diameter \>15mm), cerebral hemorrhage, subarachnoid hemorrhage;
2. History of cerebral cortex infarction.
3. History of cerebrovascular malformation or aneurysmal subarachnoid hemorrhage, or discovery of an untreated aneurysm \> 3mm.
4. Carotid or vertebral artery stenosis \> 50% measured on North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.
5. Possible amyloid cerebrovascular disease with at least 2 lobar hemorrhagic lesions (i.e., intracranial hemorrhage, cerebral microbleeds (CMB), cortical superficial siderosis, or convexal subarachnoid hemorrhage) measured on Boston Criteria 2.0; Or at least one lobar hemorrhagic lesion and at least one white matter feature (severe enlarged perivascular space in the centrum semiovale or multiple punctate white matter hyperintensities) without deep hemorrhagic lesion (cerebral hemorrhage or CMB) on T2\* weighted MRI.
6. Recorded diagnosis of neurodegenerative diseases (e.g. Alzheimer's disease and Parkinson's disease).
7. Definite non-vasogenic white matter lesions (e.g. multiple sclerosis, cortical dysplasia in adults, metabolic encephalopathy).
8. Other psychiatric disorders diagnosed measured on the Diagnostic and Statistical Manual of Mental Disorders - V (DSM-V) diagnostic criteria; Or apparent suicidal intent.
9. Unable to tolerate MRI or contraindication to MRI (e.g., claustrophobia).
10. T1 or T2 weighted MRI shows focal brain injury.
11. Patients or first-degree relatives with a history of seizures.
12. Implanted pacemakers, vagus nerve stimulators, deep brain stimulators, or other metal medical devices.
13. Received transcranial magnetic stimulation therapy within previous 3 months.
14. Severe organic diseases with expected survival time \<5 years, such as malignant tumor.
15. Women of child bearing potential, pregnant or breastfeeding.
16. Individual who have difficulty communicating verbally to the extent that they are unable to communicate, understand or follow instructions normally, and are unable to cooperate with treatment and evaluation.
17. Combined with alcohol and drug abuse history.
18. Unable to be cooperative and complete the follow-up due to geographical or other reasons.
19. Participated in other clinical trials.

Where this trial is running

Beijing

• Beijing Tiantan Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Weiqi Chen

Conditions Cerebral Small Vessel Diseases; Cognitive Impairment; Intermittent Theta-Burst Stimulation; Personalized Brain Function Sector