Xiaoketongbi Formula vs pregabalin for painful diabetic neuropathy: A single‐center, randomized, single‐blind, double‐dummy, and parallel controlled clinical trial

Abstract

Background We assessed the efficacy and safety of the Xiaoketongbi Formula (XF) vs. pregabalin in patients with painful diabetic neuropathy (PDN). Methods Patients with PDN (n = 68) were included in a single‐center, randomized, single‐blind, double‐dummy, parallel controlled clinical trial. The primary outcome was the change in the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI‐DPN). Secondary outcomes evaluated included the reduction of BPI‐DPN >50%, changes in the numeric rating scale‐11 (NRS‐11) score for pain, Daily Sleep Interference Diary (DSID), Patient Global Impression of Change (PGIC), nerve conduction velocity (NCV), and adverse events. Results After 10 weeks of treatment, the BPI‐DPN score reduced from 42.44 ± 17.56 to 26.47 ± 22.22 and from 52.03 ± 14.30 to 37.85 ± 17.23 in the XF and pregabalin group ( P s < 0.001), respectively. The difference in the absolute change in BPI‐DPN score between both groups was −1.79 (95% CI: −9.09, 5.50; p = 0.625). In the XF and pregabalin groups, 44.1% (15/34) and 20.6% (7/34) of patients reported a BPI‐DPN reduction >50% ( p = 0.038), respectively. There were no significant differences between groups in NRS‐11 and DSID ( P s > 0.05). A significantly greater number of patients in the XF group felt “significantly improved” or “improved” than in the pregabalin group (35.3% (12/34) vs. 11.8% (4/34), p = 0.045). The absolute change in motor nerve conduction velocity of the right median nerve was significantly different between both groups (XF group 0.7 ± 2.3 vs. pregabalin group −2.2 ± 4.1, p = 0.004). No serious adverse events were reported in either group. Conclusions XF is equivalent to pregabalin in reducing pain symptoms and improves the quality of life in patients with PDN. In addition, XF has the potential to improve nerve function by increasing NCV.

The reporting quality of randomized controlled trials in Chinese herbal medicine (CHM) formulas for diabetes based on the consort statement and its extension for CHM formulas

“…The mean adherence of the included RCTs to the CONSORT statement was 53.56% (SD 17.98%, min-max 19.35%–92.19%): 44 (61.11%) RCTs had adherence below 60% ( Tang et al, 2021 ; Zhu et al, 2022 ; Shi et al, 2022 ; Qiao et al, 2022 ; Zhan et al, 2021 ; Liu et al, 2020 ; Tassadaq and Wahid, 2019 ; Cui et al, 2019 ; Zhao et al, 2018 ; Xiao et al, 2018 ; Tian et al, 2017 ; Tang et al, 2018 ; Zhao et al, 2016 ; Wu et al, 2016 ; Zhang et al, 2015 ; Xu et al, 2014 ; Guangcan and Ligong, 2015 ; Luo et al, 2015 ; Liu H. et al, 2015 ; Lian et al, 2015a ; Zhao et al, 2014 ; Watanabe et al, 2014 ; Ma et al, 2013 ; Fang et al, 2013 ; Chen et al, 2012 ; Li F. et al, 2011 ; You et al, 2009 ; Luo et al, 2009 ; Zhang et al, 2008 ; Leung et al, 2008 ; Wei and Xie, 2007 ; Xue et al, 2006 ; Chen and Wang, 2005 ; Wang and Wang, 2005 ; Huang et al, 2004 ; Nagaki et al, 2003 ; Wu et al, 2000 ; Ren, 2000 ; Li et al, 2000 ; Li and Wang, 1999 ; Gao Y et al, 1998 ; Wang et al, 1997 ; Zhu et al, 1992 ), and only 4 (5.56%) had adherence above 80% ( Lian et al, 2015b ; Li et al, 2015 ; Huang et al, 2019 ; Lu et al, 2022 ). The reporting quality of the CONSORT statement tended to increase over time based on the publication year ( Figure 2A ).…”

“…The mean CHM Formula extension reporting compliance for the included RCTs was 45.71% (SD 11.15%, min-max 25%–72.73%): 39 (54.17%) of these RCTs had an adherence rate lower than 50% ( Hale et al, 1989 ; Zhu et al, 1992 ; Wang et al, 1997 ; Li and Wang, 1999 ; Ren, 2000 ; Nagaki et al, 2003 ; Huang et al, 2004 ; Chen and Wang, 2005 ; Wang and Wang, 2005 ; Xue et al, 2006 ; Leung et al, 2008 ; Zhang et al, 2008 ; Chao et al, 2009 ; Li S. et al, 2011 ; Li F. et al, 2011 ; Leung et al, 2012 ; Grant et al, 2013 ; Ji et al, 2013 ; Ma et al, 2013 ; Tong et al, 2013 ; Tsai et al, 2013 ; Ko et al, 2014 ; Xu et al, 2014 ; Lian et al, 2015a ; Lian et al, 2015b ; Li et al, 2015 ; Zhang et al, 2015 ; Hu et al, 2016a ; Hu et al, 2016b ; Wu et al, 2016 ; Yang et al, 2016 ; Tian et al, 2017 ; Liu et al, 2018 ; Tong et al, 2018 ; Cui et al, 2019 ; Shi et al, 2019 ; Tassadaq and Wahid, 2019 ; Lu et al, 2022 ; Zhang et al, 2022 ). The improving trend of reporting quality of the CHM formula extension over time was not as significant as the CONSORT statement ( Figure 2B ).…”

“…Less than 10% of the RCTs reported all 7 items: title (1a), abstract (1b), keyword (1c), introduction (2b), participants (4a), interventions for CHM Formula ( Lee et al, 2022 ), and generalizability ( Lu et al, 2022 ). Among these included trials, 49 (68.06%) RCTs did not report outcome measures with TCM patterns ( Shi et al, 2019 ; Zhu et al, 2022 ; Zhang et al, 2022 ; Shi et al, 2022 ; Lu et al, 2022 ; Zhang Y. et al, 2019 ; Tassadaq and Wahid, 2019 ; Cui et al, 2019 ; Zhao et al, 2018 ; Tong et al, 2018 ; Tian et al, 2017 ; Tang et al, 2018 ; Liu et al, 2018 ; Zhao et al, 2016 ; Yang et al, 2016 ; Wu et al, 2016 ; Hu et al, 2016a ; Hu et al, 2016b ; Qiang et al, 2016 ; Chui et al, 2016 ; Zhang et al, 2015 ; Xu et al, 2014 ; Qiang et al, 2015 ; Luo et al, 2015 ; Liu H. et al, 2015 ; Lian et al, 2015a ; Lian et al, 2015b ; Ko et al, 2014 ; Tu et al, 2013 ; Tsai et al, 2013 ; Tong et al, 2013 ; Ma et al, 2013 ; Grant et al, 2013 ; Leung et al, 2012 ; Chen et al, 2012 ; Li S. et al, 2011 ; Li F. et al, 2011 ; Chao et al, 2009 ; Zhang et al, 2008 ; Leung et al, 2008 ; Xue et al, 2006 ; Chen and Wang, 2005 ; Wang and Wang, 2005 ), while 67 (93.06%) RCTs did not explore the applicability of trial findings to different TCM patterns ( Fang et al, 2013 ; Grant et al, 2013 ; Ji et al, 2013 ; Ma et al, 2013 ; Tong et al, 2013 ; Tsai et al, 2013 ; Tu et al, 2013 ; Ko et al, 2014 …”

“…Frontiers (Hale et al, 1989;Grant et al, 2013;Tu et al, 2013;Ko et al, 2014;Watanabe et al, 2014;Li et al, 2015;Luo et al, 2015;Qiang et al, 2016;Zhao et al, 2016;Tang et al, 2018;Tong et al, 2018;Yu et al, 2018;Lu et al, 2022;Zhang et al, 2022) for the primary outcome. In addition, the median sample size was 95 (IQR 62-149.25) and the median number of authors was 6 (IQR 4-10.75) in the included RCTs.…”

Advances of traditional Chinese medicine preclinical mechanisms and clinical studies on diabetic peripheral neuropathy

“…No serious adverse effects were reported during the trial indicating the safety of XF (Lu et al. 2022 ).…”