Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial

Jing Shi, Mingqing Wei, Jingnian Ni, Feng Sun, Li Sun, Junfu Wang, Tao Yu, Kai Wang, Peiyuan Lv, Yunfu Wang, Yulian Zhang, Xuguang Gao, Xuanzhao Gao, Benyan Luo, Shanping Mao, Baorong Zhang, Xiangyang Ren, Fengchun Yu, Wenli Hu, Ping Yin, Nanjin Wu, Xianfeng Liu, Qi Bi, Yongyan Wang, Jinzhou Tian, CHASE Study Group, Jing Shi, Mingqing Wei, Jingnian Ni, Feng Sun, Li Sun, Junfu Wang, Tao Yu, Kai Wang, Peiyuan Lv, Yunfu Wang, Yulian Zhang, Xuguang Gao, Xuanzhao Gao, Benyan Luo, Shanping Mao, Baorong Zhang, Xiangyang Ren, Fengchun Yu, Wenli Hu, Ping Yin, Nanjin Wu, Xianfeng Liu, Qi Bi, Yongyan Wang, Jinzhou Tian, CHASE Study Group

Abstract

Background and purpose: Tianzhi granule (TZ) is usually used for patients with vascular dementia (VaD) in China. The aim was to assess the effect of TZ by a randomized clinical trial (RCT).

Methods: A 24-week RCT was conducted in 16 centres. Participants were grouped into TZ, donepezil or placebo. The co-primary outcomes were the Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog) and Clinician's Interview-based Impression of Change-plus caregiver information (CIBIC-plus).

Results: A total of 543 patients with mild to moderate VaD were enrolled, of whom 242 took TZ granules, 241 took donepezil, and 60 took placebo. The least-squares mean changes from baseline and 95% CI were 6.20 (5.31, 7.09) (TZ group), 6.53 (5.63, 7.42) (donepezil group) and 3.47 (1.76, 5.19) (placebo group), both TZ and donepezil showed small but significantly improvement compared with placebo group. The percent of improvement on the global impression which was measured by CIBIC-plus was 73.71% in TZ and 58.18% in placebo, there was significant different between TZ and placebo group (P = 0.004). No significant differences were observed between TZ and donepezil. No significant differences of adverse events were found.

Conclusions: TZ and donepezil could bring symptomatic benefit for mild to moderate VaD. Trial registration The protocol had retrospectively registered at clinical trial.gov, Unique identifier: NCT02453932, date of registration: May 27, 2015; https://www.clinicaltrials.gov/ct2/show/NCT02453932?term=NCT02453932&rank=1.

Keywords: Behavioral and psychological symptoms of dementia; Herbal medicine; Randomized controlled trial; Tianzhi granule; Vascular dementia.

Conflict of interest statement

XF Liu, F Sun are employees of Zhongjing Wanxi Pharmaceutical Co., Ltd, Zhongjing Wanxi Pharmaceutical Co., Ltd supplied the study drugs for this clinical trial, other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The study flow diagram. ITT Intent-to-treat
Fig. 2
Fig. 2
The primary efficacy measures at endpoint (ITT-LOCF analysis). a VADAS-cog mean change from baseline score in three groups. VADAS-cog Vascular Dementia Assessment Scale-Cognitive Subscale (VADAS-cog). p < 0.05 Tianzhi vs placebo in the mean change after 24 weeks’ treatment, p < 0.05 donepezil vs placebo in the mean change after 24 weeks’ treatment, p > 0.05 Tianzhi vs donepezil. ITT intent-to-treat, LOCF last observation carried forward, PPS per protocol set. b CIBIC-plus at endpoint (week 24) in three groups. CIBIC-plus Clinician Interview-Based Impression of Change scale Clinician’s Interview-Based Impression of Change–plus version. Overall treatment p < 0.01. p < 0.01 Tianzhi vs placebo, p < 0.01 donepezil vs placebo, p > 0.05 donepezil vs Tianzhi
Fig. 3
Fig. 3
Mean change of secondary efficacy measures from baseline in three groups (ITT-LOCF analysis). a Mean change of NPI from baseline in three groups. b Mean change of MMSE from baseline in three groups. MMSE Mini-mental state examination, NPI Neuropsychiatric Inventory. p < 0.05 Tianzhi vs placebo in the mean change after 24 weeks’ treatment, p < 0.05 donepezil vs placebo in the mean change after 24 weeks’ treatment, p > 0.05 Tianzhi vs donepezil. ITT intent-to-treat, LOCF last observation carried forward, PPS per protocol set

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