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.
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.
Study Type
Participants in active group will receive iTBS stimulation in 50-Hz triplets at 5 Hz for 600 seconds per session (2 seconds on and 8 seconds off) at 90% of their resting motor threshold to the left dorsolateral prefrontal cortex (DLPFC).Each intervention day includes 4 sessions (1800 pulses/session) of stimulation delivering a total of 7200 active pulses. This treatment protocol will be conducted 15 consecutive days.
Participants in the sham group will receive sham iTBS stimulation, which will use the same stimulation parameters, dosage, and duration as the active group, but will employ a sham coil. The sham coil is identical in appearance to the real stimulus coil and simulate the sound of a real stimulus, but do not produce a real stimulus.
Beijing Tiantan Hospital
Beijing, China
RECRUITINGChange from baseline in Montreal Cognitive Assessment Scale
Montreal Cognitive Assessment Scale (Beijing Edition) scores from 0 to 30. A higher score indicates better cognitive function.
Time frame: at 90±7days after iTBS therapy
Change from baseline in Mini-mental State Examination
Mini-mental State Examination (MMSE) scores from 0 to 30. A higher score indicates better cognitive function.
Time frame: at 90±7days after iTBS therapy
Change from baseline in verbal fluency test
Scoring of verbal fluency test (VFT) is based on the number of words produced by the participants from a category in a given time. A higher score indicates better cognitive function.
Time frame: at 90±7days after iTBS therapy
Change from baseline in trail making test
Scoring of color trial test (CTT) is based on time taken to complete the test and the number of wrong answers. Shorter the test time and less the mistakes, the better the outcome.
Time frame: at 90±7days after iTBS therapy
Change from baseline in Stroop Test
Scoring of Stroop Test is based on time taken to complete the test and the number of wrong answers. Shorter the test time and less the mistakes, the better the outcome.
Time frame: at 90±7days after iTBS therapy
Change from baseline in digital span test
Digital span test scores from 0 to 24. A higher score indicates better cognitive function.
Time frame: at 90±7days after iTBS therapy
Change from baseline in Hamilton Anxiety Scale
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INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
58
Hamilton Anxiety Scale (HAMA) scores from 0 to 56. A lower score indicates better emotional state.
Time frame: at 15±7days and 90±7days after iTBS therapy
Change from baseline in Hamilton Depression Scale
Hamilton Depression Scale (HAMD) scores from 0 to 68. A lower score indicates better emotional state.
Time frame: at 15±7days and 90±7days after iTBS therapy
Change from baseline in Pittsburgh sleep quality index
Pittsburgh sleep quality index (PSQI) scores from 0 to 21. A lower score indicates better sleep quality.
Time frame: at 15±7days and 90±7days after iTBS therapy
Change from baseline in The Short Physical Performance Battery(SPPB)
SPPB scores from 0 to 12. A higher score indicates better motor ability.
Time frame: at 15±7days and 90±7days after iTBS therapy
Change from baseline in The 5-level EuroQol five Dimensions Questionnaire
The 5-level EuroQol five Dimensions Questionnaire (EQ-5D-5L) scores from 0 to 25. A lower score indicates better life quality.
Time frame: at 15±7days and 90±7days after iTBS therapy
Change from baseline in 6 meter walk test
Scoring of 6 meter walk test is based on time taken to complete the test. A lower score indicates better motor ability.
Time frame: at 15±7days and 90±7days after iTBS therapy
Change from baseline in step-by-step walk test
Step-by-step walk test scores from 0 to 8. A lower score indicates better motor ability.
Time frame: at 15±7days and 90±7days after iTBS therapy
Change from baseline in 3-dimensional gait analysis (3D-IGA)
Gait features can be assessed with 3D-IGA providing rhythm, pace, phases, joint angle and other quantitative indicators.
Time frame: at 15±7days and 90±7days after iTBS therapy