Clinical trial NCT06579664: Intermittent Theta Burst Stimulation on Cognitive Impairment of Cerebral Small Vessel Disease
Official title: Intermittent Theta Burst Stimulation on Cognitive Impairment of Cerebral Small Vessel Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cerebral Small Vessel Diseases
Cognitive Impairment
Keywords: Cerebral Small Vessel Diseases
Cognitive Impairment
Intermittent Theta-Burst Stimulation
Personalized Brain Function Sector
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2024-08-30
Enrollment: 58
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial was a randomized, single-center, double-blind, sham-controlled parallel trial. Participants were randomly assigned to receive iTBS stimulation or sham stimulation for 3 weeks in 1:1 ratio.
Primary purpose: TREATMENT

Brief summary: The cerebral small vessel diseases (CVSD) can cause severe and lasting damage to cognition function while the current available treatment of vascular cognitive impairment (VCI) is limited. The purpose of this study is to explore the feasibility, safety, and efficacy of intermittent Theta Burst Stimulation (iTBS) on cognitive impairment of cerebral small vessel disease.

Detailed description: The cerebral small vessel diseases(CSVD) refers to any pathologic process that damages small end arteries, arterioles, venules, and brain capillaries. CVSD can cause severe and lasting damage to cognition function while the current available treatment of vascular cognitive impairment (VCI) is limited. Repetitive transcranial magnetic stimulation, a noninvasive neuromodulation treatment, has been proven effective for various neurological diseases such as depression, Parkinson's disease, poststroke movement disorders, and cognitive impairment. Theta-burst stimulation (TBS) has recently attracted broad attention as a form of accelerated repetitive transcranial magnetic stimulation that is more effective in achieving similar or higher therapeutic effects than conventional repetitive transcranial magnetic stimulation. The intermittent TBS (iTBS) has been considered to enhance cortical excitability. Personalized Brain Function Sector (pBFS) is a method that accurately delineate whole-brain personalized functional networks utilizing resting-state functional magnetic resonance imaging (MRI). The purpose of this study is to explore the efficacy and safety of iTBS under the guidance of pBFS in improving cognitive function in patients with CSVD.

This trial was a randomized, single-center, double-blind, sham-controlled parallel trial. The trial planned to enroll 58 patients with clinical evidence of CVSD and cognitive impairment, aged 45-85 years.

Participants were randomly assigned to receive iTBS stimulation or sham stimulation for 3 weeks in 1:1 ratio.

iTBS group: iTBS stimulation to the left dorsolateral prefrontal cortex (DLPFC), 1800 pulses /session, 4 sessions /day, as well as standard treatment and management according to the related guidelines.

sham iTBS group: mimicked iTBS stimulation at the same stimulation parameters, dose, and duration as the iTBS group with a sham coil, as well as standard treatment and management according to the related guidelines.

Follow up: Face to face interviews will be made on baseline, 15±7 days after randomization and 90±7 days after iTBS intervention.

The score of Montreal Cognitive Assessment Scale (MoCA) 90 days after iTBS intervention will be tested by the t-test or the Wilcoxon rank-sum test. The change of MoCA between baseline and 90 days after iTBS intervention will be tested by the two-sample t-test or the Mann-Whitney U test.

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.

Primary outcomes:
measure: Change from baseline in Montreal Cognitive Assessment Scale
timeFrame: at 90±7days after iTBS therapy
Secondary outcomes:
measure: Change from baseline in Mini-mental State Examination
timeFrame: at 90±7days after iTBS therapy
measure: Change from baseline in verbal fluency test
timeFrame: at 90±7days after iTBS therapy
measure: Change from baseline in trail making test
timeFrame: at 90±7days after iTBS therapy
measure: Change from baseline in Stroop Test
timeFrame: at 90±7days after iTBS therapy
measure: Change from baseline in digital span test
timeFrame: at 90±7days after iTBS therapy
measure: Change from baseline in Hamilton Anxiety Scale
timeFrame: at 15±7days and 90±7days after iTBS therapy
measure: Change from baseline in Hamilton Depression Scale
timeFrame: at 15±7days and 90±7days after iTBS therapy
measure: Change from baseline in Pittsburgh sleep quality index
timeFrame: at 15±7days and 90±7days after iTBS therapy
measure: Change from baseline in The Short Physical Performance Battery(SPPB)
timeFrame: at 15±7days and 90±7days after iTBS therapy
measure: Change from baseline in The 5-level EuroQol five Dimensions Questionnaire
timeFrame: at 15±7days and 90±7days after iTBS therapy
measure: Change from baseline in 6 meter walk test
timeFrame: at 15±7days and 90±7days after iTBS therapy
measure: Change from baseline in step-by-step walk test
timeFrame: at 15±7days and 90±7days after iTBS therapy
measure: Change from baseline in 3-dimensional gait analysis (3D-IGA)
timeFrame: at 15±7days and 90±7days after iTBS therapy
Other outcomes:
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