Zishenpingchan granules for the treatment of Parkinson＇s disease：a randomized,double-blind,placebo-controlled clinical trial

Levodopa preparations remain the preferred drug for Parkinson＇s disease.However,long-term use of levodopa may lead to a series of motor complications.Previous studies have shown that the combination of levodopa and Zishenpingchan granules（consisting of Radix Rehmanniae preparata,Lycium barbarum,Herba Taxilli,Rhizoma Gastrodiae,Stiff Silkorm,Curcuma phaeocaulis,Radix Paeoniae Alba,Rhizoma Arisaematis,Scorpio and Centipede） can markedly improve dyskinesia and delay the progression of Parkinson＇s disease,with especially dramatic improvements of non-motor symptoms.However,the efficacy of this combination has not been confirmed by randomized controlled trials.The current study was approved by the Hospital Ethics Committee and was registered in the Chinese Clinical Trial Register（registration number：Chi CTR-INR-1701194）.From December 2014 to December 2016,128 patients（72 males and 56 females,mean age of 65.78 ± 6.34 years） with Parkinson＇s disease were recruited from the Department of Neurology of Longhua Hospital and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine in China.Patients were equally allocated into treatment and control groups.In addition to treatment with dopamine,patients in treatment and control groups were given Zishenpingchan granules or placebo,respectively,for 24 weeks.Therapeutic efficacy was assessed using the Unified Parkinson＇s Disease Rating Scale,on-off phenomenon,Hoehn-Yahr grade,Scales for Outcomes in Parkinson＇s disease–Autonomic,Parkinson＇s disease sleep scale,Hamilton Anxiety Scale,Hamilton Depression Scale,Mini-Mental State Examination,and the Parkinson＇s Disease Quality of Life Questionnaire.Artificial neural networks were used to determine weights at which to scale these parameters.Our results demonstrated that Zishenpingchan granules significantly reduced the occurrence of motor complications,and were useful for mitigating dyskinesia and non-motor symptoms of Parkinson＇s disease.This combination of Chinese and Western medicine has the potential to reduce levodopa dosages,and no obvious side effects were found.These findings indicate that Zishenpingchan granules can mitigate symptoms of Parkinson＇s disease,reduce toxic side effects of dopaminergic agents,and exert synergistic and detoxifying effects.

Efficacy and safety of Tianqi Pingchan Granule,a compound Chinese herbal medicine,for levodopa-induced dyskinesia in Parkinson’s disease:A randomized double-blind placebo-controlled trial

Background Patients with Parkinson’s disease(PD)undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia(LID).Amantadine is the main drug recommended for the treatment of LID by current guidelines,but it is far from meeting clinical needs.Tianqi Pingchan Granule(TPG),a compound Chinese herbal medicine,has been developed to relieve symptom of LID.Objective This randomized controlled trial evaluated the efficacy and safety of the combination of TPG and amantadine for LID.Design,setting,participants and interventions This is a randomized double-blind placebo-controlled trial,conducted from January 2020 to August 2021 at 6 sites in Jiangsu,Zhejiang and Shanghai,China.One hundred PD patients with≥0.5 h of LID were randomly assigned to either the TPG plus amantadine group(TPG group)or the placebo plus amantadine group(placebo group),and treated for a period of 12 weeks.To ensure unbiased results,all study participants,investigators and sponsors were unaware of group allocations.Additionally,the data analysts remained blinded until the analysis was finalized.Main outcome measures The primary outcome was assessed using the Unified Dyskinesia Rating Scale(UDysRS)(Range 0–104).The key secondary end point was improvement of motor and non-motor symptoms.Safety analyses included all enrolled patients.Results One hundred patients were enrolled and randomized into the two treatment groups.The changes in UDysRS at week 12 were–11.02 for the TPG group and–4.19 for the placebo group(treatment difference–6.83[–10.53 to–3.12];P=0.0004).Adverse events were reported for 2 of 50 patients(4.0%)in each of the groups.Conclusion This study indicated that a 12-week treatment of amantadine plus TPG effectively reduced UDysRS scores and was well tolerated,demonstrating the efficacy and safety of TPG for the treatment of LID in PD.

Pingchan granule for depressive symptoms in parkinson’s disease:A randomized,double-blind,placebo-controlled trial

Background:Depression in Parkinson’s disease(dPD)is closely related to quality of life.Current studies have suggested that Pingchan Granule(PCG)might be effective for treating dPD.Objective:This study determines the efficacy of PCG for depressive symptoms in Parkinson’s disease(PD).Design,setting,participants and interventions:This was a randomized,double-blind,placebo-controlled trial,conducted in Longhua Hospital,Shanghai,China.Patients diagnosed with idiopathic PD and clinically significant depressive symptoms(defined by a 24-item Hamilton Rating Scale for Depression[HAM-D]score≥8)were included in this study,randomly assigned to PCG or placebo group in a 1:1 ratio and followed for 24 weeks.Main outcome measures:The primary outcome was the change from baseline to week 24 in HAM-D score among the set of patients who completed the study following the treatment protocol(per-protocol set).Secondary outcomes included changes in scores on the Unified Parkinson’s Disease Rating Scale(UPDRS)part 2(UPDRS-Ⅱ),UPDRS part 3(UPDRS-Ⅲ),Parkinson’s Disease Sleep Scale(PDSS)and Hamilton Rating Scale for Anxiety(HAM-A),between baseline and week 24.Results:Eighty-six patients were enrolled,and 85 patients were included in the per-protocol set.HAM-D scores decreased by an adjusted mean of 11.77(standard error SE 0.25)in the PCG group and 3.86(SE0.25)in the placebo group(between-group difference=7.91,95%confidence interval[7.22,8.80],P<0.001),in the multivariable linear regression.Improvements in scores on the UPDRS-II,UPDRS-III,PDSS,and HAM-A scales were also observed.Conclusion:Treatment with PCG was well tolerated and improved depressive symptoms and motor and other non-motor symptoms in PD.Trial registration:Chinese Clinical Trial Register:ChiCTR-INR-17011949.