A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble Yeast Beta-Glucan to Improve the Immune Defense System

Purpose: In a placebo-controlled, double-blind, randomized clinical trial, the effect of an insoluble yeast beta-glucan preparation on the incidences of common colds and its effect on common cold symptoms were compared to placebo. Methods: 100 healthy participants with recurring infections were randomly assigned to receive either placebo or yeast beta-glucan (Yestimun?;n = 50 each group) over a period of 26 weeks. The subjects had to document each common cold episode in a diary, and rate 6 predefined infections symptoms on a 3-point rating scale during an infection period, resulting in an infection score. The common cold episodes were confirmed by the investigators. Results: A total of 171 common cold episodes were documented. Of these, 76 were experienced by 38 subjects in the beta-glucan group and 96 were experienced by 48 subjects in the placebo group (p = 0.406). The beta-glucan group had significantly more subjects without incidences of common cold than the placebo group (15.6% vs 2.0%;p = 0.019). During the most intense infection season (first 13 weeks of the study), the beta-glucan group had significantly less infections compared to placebo (p = 0.02). Beta-glucan significantly reduced the typical cold symptoms (“sore throat and/or difficulty swallowing”, “hoarseness and/or cough” and “runny nose”) as opposed to placebo. Conclusion: The present study demonstrates a prophylactic effect of yeast beta-glucan on the occurrence of common colds as opposed to placebo. In addition, when these episodes occurred, they were from the beginning less pronounced and subsided faster.

Immunomodulatory Activities of a Concentrated Fruit and Vegetable Juice Tested in a Randomized,Placebo-Controlled,Double-Blind Clinical Trial in Healthy Volunteers

22 healthy volunteers were included in a randomized, placebo-controlled pilot study in order to investigate immunomodulatory effects of a concentrated juice, containing the ingredients of a total of 80 different fruits, vegetables, herbs, mushrooms, oils, and others (Cellagon aurum?, “CA”). 11 subjects received the concentrated juice while 11 were allocated to the placebo group. Stimulated whole-blood cultures were used to assess any treatment-related changes in the response of leukocytes towards experimental immune cell activation. For each of the individuals, 5 cultures were performed either immediately before, during, or 3 days after termination of the 7 weeks treatment. Leukocyte activities were determined by measuring cytokine levels in the supernatants at the end of the 48 h of stimulation (induced by the addition of LPS + SE-B + anti-CD28 antibodies). Despite the relatively small number of volunteers, multiplexed cytokine assays revealed a typical T-cell signature of cytokines that were increased significantly in the course of CA treatment compared to placebo (GM-CSF, IFNγ, IL-4, IL-10, IL-17, TNFβ, all p 0.05). These preliminary results suggest that CA is able to support leukocyte activation, in particular that of T-lymphocytes.

Effect of <i>Lactobacillus brevis</i>SBC8803 on Gamma-Glutamyl Transferase in Japanese Habitual Drinkers: A Double-Blind, Placebo-Controlled Study

A randomized, double-blind, placebo-controlled clinical trial in Japanese habitual drinkers was conducted to evaluate the efficacy of Lactobacillus brevis SBC8803 to alleviate adverse effect of alcohol. Subjects who drank habitually and had moderately higher levels of gamma-glutamyl transferase (GGT) (50 - 100 IU/L) were enrolled. The levels of transaminases in these subjects were almost within normal levels (aspartate transaminase (AST) <30 IU/L and alanine transaminase (ALT) <40 IU/L). Either the capsules containing placebo (n = 23) or 130 mg (4.0 × 1010 colony-forming units) of live L. brevis SBC8803 (n = 22) per day were administered for the continuous eight weeks (56 days). During the period, the subjects both in test group and placebo groups have kept each drinking behavior as usual. Regarding lipid metabolism, triacylglycerol (TG) levels in the male test group significantly decreased at week 4 as compared with week 0. Biomarkers of hepatocytes-damage;AST and ALT levels showed no significant differences between the pla- cebo and test groups at both weeks 4 and 8. Oxidative stress marker;GGT at weeks 4 was significantly lower in the test group than that in the placebo group (p = 0.017), but not at weeks 8. However, taking a reduced rate of GGT at weeks 8 comparing with that at week 0, that in the test group showed larger value comparing with that in the placebo group. These data about TG and GGT suggest that, although efficacy of L. brevis SBC8803 is limited in this study, intake of the probiotic may alleviate alcoholic influence in lipid metabolism and oxidative stress.

Tolerability of a Proprietary Larch Arabinogalactan Extract: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial in Healthy Subjects

In a placebo-controlled, double-blind, randomized clinical trial, the tolerability of a proprietary larch arabinogalactan preparation (ResistAidTM) was investigated. METHODS: 199 healthy participants were randomly assigned to receive either placebo (n = 98) or an arabinogalactan preparation (n = 101) over a period of 12 weeks. As safety parameters the total number of adverse events, changes in various biochemical and laboratory parameters as well as the global evaluation of tolerability by investigator and subjects compared to placebo were evaluated. RESULTS: In total 16 adverse events were observed in 16 subjects, with no difference between the arabinogalactan and the placebo group (p = 0.935). There were no differences in the mean changes of the measured biochemical and laboratory parameters. The tolerability of the arabinogalactan extract was rated as “very good” or “good” by the investigators for 99% of the subjects and by 98% subjects in self-assessment with no statistical differences to placebo. CONCLUSION: The measured parameters as well as the evaluation of the tolerability by the investigators and the subjects demonstrate a very good tolerance profile of the proprietary arabinogalactan extract with no differences to placebo when taken for 12 weeks.

Xi-Feng-Hua-Shi granules for diarrhea-predominant irritable bowel syndrome:protocol for a randomized,double-blind,placebo-controlled multi-center clinical trial

Background:Irritable bowel syndrome(IBS)is a common functional bowel disorder that can severely affect the quality of life of patients.Limited drugs have been reported for modern medical IBS treatment.The advantages of traditional Chinese medicine(TCM)treatment are gradually becoming prominent.Xi-Feng-Hua-Shi granules have been clinically used for diarrhea-predominant IBS(IBS-D)treatment for many years in TCM practice.Thus,this study aimed to further verify the effectiveness and safety of Xi-Feng-Hua-Shi(XFHS)granules in IBS-D treatment through a randomized,double-blind,placebo-controlled multi-center clinical trial and provide high-quality evidence for its effectiveness and safety in treatment,as well as provide a basis for clinical rational drug use and explore new clinical IBS-D treatment plans.Methods:A randomized,double-blind,placebo-controlled multi-center clinical trial will be performed in 23 hospitals.A total of 300 participants will be randomly divided into the experimental group(prescribed with XFHS granules)and the control group(prescribed with the placebo granules),with 150 participants in each group.The appearance,shape,color,and taste of the placebo granules are the same as those of XFHS granules.All participants will receive a 4-week treatment and a 6-month follow-up.The primary outcome is the overall clinical efficacy;the secondary outcomes are the IBS-Symptom Severity Score(IBS-SSS),TCM Syndrome Evaluation,and the IBS-Quality of Life(IBS-QoL)score,mental state assessment,and recurrence rate.Outcome measures(including primary and secondary outcome measures)are collected at baseline,as well as 2,4,16,and 28 weeks post-intervention.Discussion:This randomized,placebo-controlled,multi-center trial may provide high-quality evidence for the clinical XFHS granule efficacy in IBS-D treatment.Additionally,this study will conduct safety evaluations to provide a basis for clinical rational drug use.

Efficacy of Curcumin on Cognitive Function Scores in Women with Premenstrual Syndrome and Dysmenorrhea: A Triple-Blind, Placebo-Controlled Clinical Trial

Objective: To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome(PMS) and dysmenorrhea. Methods: A randomized, triple-blind, placebocontrolled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days(7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups. Results: Administration of curcumin was associated with a significant increase in memory score(P=0.002), inhibitory control and selective attention(P=0.020), and total cognitive ability task(P=0.024). In addition, significant increments were found in scores of memory(3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively;P=0.035), inhibitory control and selective attention(3.0±3.7 vs. 0.4±3.7;P=0.027) and total cognitive abilities(8.3±12.3 vs. 2.2±12.4;P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial. Conclusion: Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention.(Registration No. IRCT20191112045424N1, available at: https://www.irct.ir)

Effectiveness and Safety of Umbilicus Treatment with Modified Dinggui Powder(加味丁桂散)in Patients with Chronic Nonbacterial Prostatitis:A Randomized,Double-Blind,Placebo-Controlled Clinical Trial

Objective:To evaluate the effectiveness and safety of Chinese herbal external umbilicus treatment with Modified Dinggui Powder(加味丁桂散,MDGP)in patients with chronic nonbacterial prostatitis(CNP).Methods:A randomized,double-blind,placebo-controlled clinical trial was conducted among 72 patients with CNP.Participants were randomly allocated to a treatment group and a placebo group using computer software in a 1:1 ratio,and received either MDGP external umbilicus treatment(MDGP group,36 cases)or placebo(control group,36 cases)at acupoints Shenque(CV 8),twice a week for 4 weeks.In addtion,patients all received herbal medicine treatment twice a day for 4 weeks.The primary outcome was the US National Institutes of Health Chronic Prostatitis Symptom Scores Index(NIH-CPSI)with a questionnaire at weeks 2 and 4.The secondary outcomes including prostatic fluid examination(white blood cells and lecithin bodies),the clinical efficacy evaluation,and the adverse events were also assessed during the entire trial.Results:The NIH-CPSI scores regarding pain or discomfort scores showed greater improvement in the MDGP group than placebo control group at weeks 2(P=0.001)and week 4(P=0.004),respectively.NIH-CPSI scores of symptom severity,total scores and leukocytes number in the prostatic fluid in the MDGP group were significantly improved(P<0.05).There was no statistical difference in the urinary symptoms,quality of life,lecithin and other scores between two groups(P>0.05).The clinical effective rate was 73.53%(25/34)in the MDGP group,which was significally higher than the placebo control group with 48.39%(25/31,P<0.05).Patients were blinded successfully,and no serious adverse effects were found during the trial.Conclusion:A 4-week course of umbilicus treatment with modified Dinggui Powder seems to relieve pain and symptom severity effectively and increase the amount of leukocytes number in patients with CNP(Trial registration No.ChiCTRI 800014687).

Evaluation of the Potential Inhibitory Activity of A Combination of L.Acidophilus,L.Rhamnosus and L.Sporogenes on Helicobacter Pylori：A Randomized Double-Blind Placebo-Controlled Clinical Trial

Objective： To investigate whether three strains of probiotics, L. acidophilus, L. rhamnosus, and L. sporogenes, had significant inhibitive effects on Helicobacter pylori（H. pylori）. Methods： This is a 4-week, randomly assigned, parallel-group, doubled-blind, and placebo-controlled study. Fifty patients with a positive H. pylori infection urea breath test（△UBT） result 〉 10% and without ulcer symptoms were randomized into a treatment group and a placebo group by a computer generated allocation sheet with 1：1. These subjects took one capsule of probiotics or placebo twice daily. The primary measurement was the change in △UBT values. Results： The △UBT values during the 4-week treatment period and the 2-week follow-up period were not significantly different between the treatment group and the placebo group, indicating that the inhibitive effects on H. pylori were comparable between both groups. The monocyte count（%） was 5.77±1.11 in the treatment group versus 5.09±1.12 in the placebo group（P=0.044）, and the basophile count was 0.55±0.32 in the treatment group versus 0.36±0.23 in the placebo group（P=0.024） at week 2 of the treatment period, both of which reached statistical significance. The monocyte count was 5.75±1.26 in the treatment group and 4.72±0.99 in the placebo group at the end of the follow-up period（P=0.003）. Conclusions： There was no significant inhibitive effects of the three probiotic strains（L. acidophilus, L. rhamnosus, and L. sporogenes） on H. pylori. Probiotics can not play the same role as antibiotics in the eradication of H. pylori, the role of probiotics is likely to be important as adjuvant to the triple or quadruple therapy for H. pylori, especially in resistance cases.

Phase Ⅱb trial of in vivo electroporation mediated dualplasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.

Losartan to prevent hyperenzymemia after endoscopic retrograde cholangiopan-creatography: A randomized clinical trial

AIM: To study if the angiotensin II receptor blockers (ARB) losartan counteracts pancreatic hyperenzymemia as measured 24 h after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A triple-blind and placebo-controlled randomized clinical trial was performed at two Swedish hospitals in 2006-2008. Patients over 18 years of age undergoing ERCP, excluding those with current pancreatitis, current use of ARB, and severe disease, such as sepsis, liver and renal failure. One oral dose of 50 mg losartan or placebo was given one hour before ERCP. The relative risk of hyperenzymemia 24 h after ERCP was estimated using multivariable logistic regression, and expressed as odds ratio with 95% confidence intervals (CIs), including adjustment for potential remaining confounding. RESULTS: Among 76 participating patients, 38 were randomized to the losartan and the placebo group, respectively. The incidence rates of hyperenzymemia and acute pancreatitis among all 76 participating patients were 21% and 12%, respectively. Hyperenzymemia was detected in 9 and 7 patients in the losartan and placebo group, respectively. There were no major differences between the comparison groups regarding cannulation difficulty, findings, or proportion of patients requiring drainage of the bile ducts. There were, however, more pancreatic duct injections, a greater extent of pancreatography, and more biliary sphincterotomies in the losartan group than in the placebo group. Losartan was not associated with risk of hyperenzymemia compared to the placebo group after multi-varible logistic regression analysis (odds ratio 1.6, 95%CI 0.3-7.8). CONCLUSION: In this randomized trial 50 mg losartan given orally had no prophylactic effect on development of hyperenzymemia after ERCP.

USE OF CHRONOLITHOTHERAPY FOR BETTER INDIVIDUAL HEALTHCARE AND WELFARE

Man＇s innate clocks functioning allows to understand WHEN and WHY therapies are efficient. Vigil chronotypes determination and respect allows to avoid scholars＇ failure. Performances depend on chronotypes and time changes. Both minimal and maxima/durations of night sleep cycles result from interactions between endogenous and exogenous clocks. Our ecoexotope is structured by solar, lunar and terrestrial rhythms which are synchronisers for endophysiotope clocks. Man night sleep changes depend on lunar cycles entrainment. Sleep analyses point to circa-annual solar rhythms used as controls to evidence circa-monthly lunar ones. To evidence physiological responses individual longitudinal records are used. To evidence lithotherapeutic effects, stimuli responses are tested according to a double-blind placebo-controlled survey. WHAT mineral to chose？, WHY？, HOW to treat？, WHEN？ Compared with controls, jadeite or nephrite enhances night sleep quality with a 15 fold decrease of awakenings and urinations. The highest placebo effect was below 4 fold increase. Depending on minerals and trace elements, properties change. The mineral crystal structure is evidenced to have an action. The contact area with the skin is a limiting factor. Placebo effects are greater during the day phase. Red jasper treatment enhances the number and intensity of diurnal physical working. Minerals act in a dose-dependent manner and in synergy. Hematite sole gives a placebo effect, but increases the effect of serpentinite by a 15 fold value. Within a clocks network, the latency phase of the whole is shorter than the shortest latency phase of each clock, enhancing the system reactivity.

A PROSPECTIVE STUDY TO EVALUATE THE SAFETY AND EFFICACY USING REMOVING BLOOD STASIS HERBALS FOR PATIENTS WITH INTRACRANIAL HEMORRHAGE OF HYPERACUTE STAGE AND RELATIVE FACTORS OF HEMATOMA ENLARGEMENT(A MULTICENTER PROSPECTIVE RANDOMIZED DOUBLE-BLIND PLACEBO

The aim was to investigate whether using a removing blood stasis method in hyperacute intracranial hemorrhage stage can lead to hematoma enlargement and its clinical efficacy.A multicenter retrospective randomized double-blind placebo-controlled clinical study.We recruited patients aged 18 years or older and presenting at less than 6 h from symptom onset in 8 research centers.All the patients