Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial

Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.

Efficacy of acupuncture and moxibustion in treating Bell’s palsy: a multicenter randomized controlled trial in China

Background Bell’s palsy involves acute facial paralysis due to inflammation of the facial nerve. Acupuncture and moxibustion (acu-moxi) is beneficial in treating facial palsy. In order to verify the efficacy of acu-moxi on Bell’s palsy, a randomized single-blind, multicenter clinical trial was performed.Methods A total of 480 patients from four clinical centers were involved in this trial, of whom 439 completed the trial and 41 did not. All patients were randomly assigned to either the control group or to one of two treatment groups. The control group was treated with prednisone, vitamin B_1, vitamin B_ 12, and dibazole; the treatment groups were treated either with acu-moxi alone or in combination with prednisone, Vitamin B_1, vitamin B_ 12, and dibazole. Symptoms and signs, the House-Brackmann scale, and facial disability index (FDI) scores were assessed and determined both pre- and post-treatment to evaluate the effectiveness of the treatment methods.Results The characteristics of the control and two treatment groups were comparable without statistically significant differences before treatment. There were significant differences between the control and treatment groups after treatment (χ2=15.265, P=0.018). According to evaluations based on the House-Brackmann scale and FDI scores, the effectiveness of treatment in the two treatment groups was better than in the control group and was most effective in patients receiving acu-moxi treatment alone (Z=-2.827, P=0.005). Conclusion The efficacy of acu-moxi treatment for Bell’s palsy is verified scientifically.

Multicenter randomly controlled trial on acupoint injection therapy with Chinese herbal medicines for oculomotor paralysis

Objective To evaluate the clinical effect of acupoint injection therapy for paralysis of oculomotor nerve with Chinese herbal medicines. Methods A total number of 456 patients from 3 centers with paralysis of oculomotor nerve were randomly divided into an acupoint injection group and a control group with 228 cases each. Patients in the acupoint injection group were treated with injection of Chinese herbal medicines to Jingming （晴明 BL 1）, Yangbai （阳白GB 14}, Sibai （四白 ST 24 Tongziliao （瞳子髎 GB I） on the affected side, and Ganshu （肝俞 BL 18） on both sides, Compound Angelica Injection was the main drug, and the corresponding acupoints and other injection drugs were also used according to differentiation of syndrome. Patients in the control group were treated with common western medicine. The treatment was given once a day, 10 times constituted one course with 3 days of interval. After 3 courses, the effect was assessed. TCM syndrome score, eyeball movement degree, the sizes of oculi rimae and pupil of the two groups were recorded before and after treatment. Results The effective rate of acupoint injection group was 91.7% （209/228）, and that of the control group was 73.6% （168/228）. There was statistical significance in comparing the difference between the two groups （P〈0.05）. TCM syndrome scores of the two groups after the treatment became less obviously than those before the treatment （P〈0.01, P〈0.05）, the score of acupoint injection group was more reduced than that of the control group （P〈0.05）. Eyeball movement degree and oculi rimae were enlarged and the pupil reduced in the affected eye in both groups after the treatment Call P〈0.05）. The musculus rectus medialis for the eyeball movement in the acupoint injection group was more improved than that of the control group, and the oculi rimae was bigger in the acupoint injection group than that in the control group （both P〈0.05）. Conclusion Acupoint injection therapy with Chinese herbal medicines has assured effect on the treatment of oculomotor paralysis.

Treatment of HBV Cirrhosis with Fuzheng Huayu Tablet(扶正化瘀片)and Entecavir:Design of a Randomized,Double-Blind,Parallel and Multicenter Clinical Trial

Background Antiviral therapy can lead to regression of fibrosis in chronic hepatitis B(CHB),but it has a limited effect on cirrhosis.Chinese medicines(CMs),particularly Fuzheng Huayu Tablet(扶正化瘀片,FZHY),have an antifibrotic effect in patients with CHB.Objective To observe the safety and efficacy of adjunctive FZHY in patients with hepatitis B virus(HBV)cirrhosis,this study was designed as a randomized,placebo-controlled,double-blind,parallel assignment,multicenter trial at 20 centers in China.The total 700 naive patients will be enrolled with compensate cirrhosis due to HBV,and randomly assigned into 2 groups,receiving entecavir(0.5 mg,daily)and FZHY placebo(1.6 g,3 times a day),or entecavir(0.5 mg,daily)and FZHY(1.6 g,3 times a day),respectively.The primary endpoint was histological improvement at week 48.The secondary outcome is the decline values of liver fibrosis using the noninvasive methods from baseline to week 48 in each arm of the study.Adverse events such as stomach upset,headache,fatigue,dizziness,nausea will be strictly recorded.Discussion Through this study,we hope to generate a solid evidence for the therapeutic strategy of HBV cirrhosis with a combination of anti-viral such as ETV and anti-fibrotic herbal product such as FZHY.Protocol version:Version 1.3,Date:2014.12.4.Trial registration number:NCT02241590.

Designing and implementing multicenter clinical randomized controlled trials on moxibustion with large samples

Implementing clinical trials with large multicenter samples is an important way to scientifically evaluate and demonstrate the curative effect of moxibustion.At present,clinical trials on moxibustion with large multicenter samples are prospering in China.It is necessary for research units to have good research professionals and technical platforms as well as a highly standardized and scientifically feasible methodology of research.Taking tasks in the ongoing national 973 project and in the sci-tech support program of the "11th 5-year plan",for example,this research captures the characteristics of moxibustion,carries out deep analysis and introduces specific methods and the important significance of clinical research tasks on moxibustion in designing multicenter plans,implementing experiments,supervising quality and strengthening compliance.

Treatment of Psoriasis Vulgaris with Medicated Thread Moxibustion of Zhuang Medicine:A Multicenter Randomized,Parallel Controlled Trial

Objective:To explore the efficacy and safety of Zhuang medicine medicated thread moxibustion(ZMTM)on psoriasis vulgaris.Methods:A multicenter,randomized,parallel controlled clinical trial was designed.A total of 241 outpatients with psoriasis vulgaris were randomly divided into a control group(120 cases)and a treatment group(121 cases)using a central block randomization from June 2015 to May 2018.The control group was treated with Western medicines alone including pidotimod dispersible tablets,vitamin B compound tablets,and compound cod liver oil-zinc oxide ointment.The treatment group was treated with ZMTM every 2 days combined with Western medicines.The two groups received continuous intervention for 30 days.The primary outcome was Psoriasis Area and Severity Index(PASI),and the secondary outcomes included Itch Rating Scale,Dermatology Quality of Life Index(DLQI),Hamilton Anxiety Rating Scale(HAMA),as well as PASI response rate.Meanwhile,adverse events were evaluated during the whole clinical trial.Follow-up was carried out 30 days after treatment.Results:There were 5 cases of shedding in this trial.In intention-to-treat analysis,236 cases were included and each group contained 118 cases.On the 30th and 60th days,PASI scores of patients in each group were significantly lower than that at baseline(P<0.01)and the PASI score reduction of the treatment group was greater than that of the control group(P<0.01).Itch Rating Scale,DLQI,and HAMA scale were decreased in both groups after treatment,and the treatment group showed a better therapeutic effect(P<0.01).The response rates of PASI 50 and 75 were significantly higher than those in the control group[81.4%(96/118),43.2%(51/118)vs.41.5%(49/118),11.0%(13/118),respectively,P<0.05].During follow-up,the improvements in scores of PASI,Itch Rating Scale,DLQI,and HAMA of the treatment group were significantly greater than those of the control group(P<0.01).The response rates of PASI 50 and 75 in the treatment group were significantly higher than those in the control group,respectively(both P<0.05).No obvious adverse reaction was found in either group.Conclusion:ZMTM combined with Western medicines showed a better therapeutic effect in the treatment of psoriasis vulgaris without obvious adverse reaction.(Trial Registration No.ChiCTR-IOR-16008159)

Efficacy and safety of Xinfeng capsule in patients with rheumatoid arthritis:a multi-center parallel-group double-blind randomized controlled trial

OBJECTIVE:To evaluate the efficacy and safety of Xinfeng capsule in patients suffering rheumatoid arthritis(RA).METHODS:A multi-center parallel-group designed,double-blind,randomized,controlled trial was conducted.Totally 304 RA patients were assigned to two groups:one group was administered Xinfeng capsule(XFC) plus the placebo of leflunomide and the other given leflunomide(LEF) plus the placebo of XFC for twelve weeks.The clinical and laboratory parameters were compared at baseline and fourth,eighth,and twelfth weeks.RESULTS:After twelve-week treatment,patients in two groups all showed some trend of effectiveness when compared in terms of American Rheumatism Association(ACR) recommended 20%,50%,70%improvement criteria,but it was insignificant.The validity in ameliorate modified disease activity score(DAS28) and laboratory indexes as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),rheumatoid factor(RF) were also found no difference.The score of health assessment questionnaire(HAQ),self-rating anxiety scale(SAS),self-rating depression scale(SDS) and quality of life questionnaire with rheumatoid arthritis(RAQOL)both lower than the first week and the changes showed no difference.However,the score of SDS dropped more in XFC group than in the other.A total of 147 adverse reaction cases were reported,which shows no difference between the two groups.The most common adverse reactions were hepatic impairment,anemia,leukocytopenia,epigastric discomfort and phalacrosis.CONCLUSION:XFC demonstrated better improvement in the scores of SDS and compared with those of LEF group.