Real-World Efficacy and Safety of Zishenyizhi Pill for Cognitive Impairment Associated With Cerebral Small Vessel Disease: Protocol for a Multicenter Prospective Observational Study
Bibliographic record
Abstract
BACKGROUND: Cerebral small vessel disease (CSVD) is a leading cause of vascular cognitive impairment, contributing to 36% to 67% of vascular dementia cases. Current therapies, primarily cholinesterase inhibitors, offer limited efficacy and significant adverse effects. Traditional Chinese medicine, particularly the zishenyizhi pill, which is a multiherb formulation targeting yin deficiency and blood stasis, has shown promise in preliminary studies but lacks robust clinical validation. OBJECTIVE: We designed this study to evaluate the real-world efficacy and safety of zishenyizhi pill combined with conventional Western therapy for CSVD-related cognitive impairment. METHODS: This multicenter, prospective, nonrandomized controlled trial enrolled 246 patients from 4 institutions in Hunan province, China. Participants were stratified into 2 groups: the intervention group received zishenyizhi pill plus standard Western therapy, whereas the control group received conventional integrated Chinese-Western therapy. Cognitive outcomes (Montreal Cognitive Assessment, Mini-Mental State Examination, Vascular Dementia Assessment Scale cognitive subscale, and Trail Making Test parts A and B), traditional Chinese medicine syndrome scores, and safety parameters were assessed over 12 weeks. RESULTS: Participant recruitment is scheduled to commence in April 2025, with an anticipated enrollment of 246 participants by December 2026. At present, patient recruitment is underway, and preliminary analysis of medical record data is being conducted. Final data collection is expected to conclude by April 2027, with results projected for publication in September 2027. CONCLUSIONS: The anticipated findings suggest that zishenyizhi pill may improve multiple cognitive domains in patients with cognitive impairment associated with CSVD while demonstrating a favorable safety profile. If validated, zishenyizhi pill could serve as a safe and effective adjunctive therapy for CSVD-related cognitive dysfunction. TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry ITMCTR2025000553; https://itmctr.ccebtcm.org.cn/mgt/project/view/-4790836881284495026. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/77661.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.034 | 0.024 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.005 | 0.004 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.004 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.004 | 0.004 |
| Insufficient payload (model declined to judge) | 0.019 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".