Efficacy and Safety of Guilingji Capsules(龟龄集胶囊)for Treating Mild-to-Moderate Cognitive Impairment:Study Protocol for A Randomized,Double-Blind,Positive-Controlled,Multicenter and Noninferiority Trial

Background:The incidence of cognitive impairment(CI)is gradually increasing,which has attracted more attention from medical researchers worldwide.Definitive mechanisms of pathogenesis remain elusive,and there are few medications that have been proven effective for CI.The utilization of Chinese herbal medicine has shown positive therapeutic effects for a broad spectrum of diseases,including CI.Objective:The purpose of this study is to evaluate the safety and efficacy of Guilingji Capsules(GLJC,龟龄集胶囊)in treating mild-to-moderate CI with Shen(Kidney)and marrow deficiency syndrome.Methods:This is a randomized,double-blind,positive-controlled,multicenter clinical trial with a noninferiority design that included 348 participants randomly divided into an experimental arm and an active comparator arm.Individuals in the experimental arm(174 cases)took 0.6 g of GLJC once a day and 19.2 mg of Gingko biloba extract mimetic 3 times a day.Individuals in the active comparator arm(174 cases)took 0.6 g of GLJC mimetic once a day and 19.2 mg of Gingko biloba extract in tablet form 3 times a day.The intervention period included two sessions over 24 weeks.The primary outcome be the effectiveness of GLJC on cognitive improvement after 24 weeks of treatment,which was defined as an increase in the Mini Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA)Scale.The secondary outcomes were improvement in independence,daily living ability,and Chinese medicine(CM)syndrome,which were measured with the Alzheimer’s disease Rating Scale-Cognitive Project(ADAS-Cog),Clinical Dementia Rating(CDR)Total Score,Activities of Daily Living(ADL)Total Score and the Chinese Medicine Symptom Scale(CM-SS),respectively.Serum acetylcholine,acetylcholinesterase,bax and bcl-2 were monitored to explore the mechanism of GLJC on CI.In addition,safety measures,including vital signs,electrocardiography,laboratory indicators(full blood count,kidney and liver function tests,routine urine test and routine stool test)and adverse events,were also recorded.Discussion:The purpose of this trial is to evaluate the efficacy and safety of GLJC in patients with mild-to-moderate CI with kidney and marrow deficiency syndrome.If successful,the results would provide a viable treatment for patients with mild-to-moderate CI.

Guilingji capsule(龟龄集胶囊)for Alzheimer's disease:secondary analysis of a randomized non-inferiority controlled trial

OBJECTIVE:To investigate the effectiveness and safety of Guilingji capsule(龟龄集胶囊,GLJC)in treatment of Alzheimer's disease(AD)patients with kidney-marrow deficiency pattern(KMDP)compared with gingko extract tablets.METHODS:This is a secondary analysis of a large-scale multicenter randomized non-inferiority clinical trial.A total of 120 AD patients with KMDP were enrolled in this study.The participants were randomly categorized into two groups:(a)GLJC group(n=60)and(b)gingko group(n=60).The GLJC group was treated with GLJC and gingko extract mimetic tablets,whereas the gingko group received gingko extract tablets and mimetic GLJC.The data on the Mini-Mental State Examination(MMSE),Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-Cog),Activities of Daily Living(ADL),and Chinese Medicine Symptom Scale(CM-SS)was evaluated at 0,12,and 24 weeks of treatment.The serum levels of acetylcholine(Ach),acetylcholinesterase(AchE),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in the participants were measured before and after 24 weeks of treatment.The safety was based on the incidence of adverse events.RESULTS:Both interventions significantly increased the MMSE scores of the participants and decreased their ADAS-Cog,ADL,and CM-SS scores(P<0.01).Compared with the gingko group,the GLJC group had a higher effective rate of improvement in the symptoms of“amnesia”and“dull expression and slow thinking”at the 12th week and 24th week(P<0.05,P<0.01).In the GLJC group,serum Bcl-2 levels were significantly increased at the 24th week(P<0.05).Serum Bax and AchE levels of the two groups were significantly decreased at the 24th week(P<0.01).No treatmentrelated adverse events were reported in the two groups.CONCLUSIONS:GLJC is equivalent to the gingko extract tablets in terms of improving cognitive function and the quality of life in AD patients with KMDP and has good clinical efficacy and safety.When it comes to improving TCM symptoms and anti-aging,GLJC is even more advantageous.