Gyejigachulbutang (Gui-Zhi-Jia-Shu-Fu-Tang, Keishikajutsubuto, TJ-18) in Degenerative Knee Osteoarthritis Patients: Lessons and Responders from a Multicenter Randomized Placebo-Controlled Double-Blind Clinical Trial

Background. Gyejigachulbutang (GUI-ZHI-JIA-SHU-FU-TANG, GCB) is an herbal formula widely prescribed in traditional East Asian medicine practice for arthritis and muscle pain. We evaluated the efficacy and safety of GCB for degenerative knee osteoarthritis (KOA). Methods. Eighty patients with KOA were randomly assigned to the GCB group or the placebo group in a 1 : 1 ratio in two Korean medicine hospitals. Patients took GCB or placebo three times a day for 4 weeks. Primary outcome was the change in the visual analogue scale (VAS) score for knee pain from baseline to 4th week. Secondary outcomes were the change in the VAS score from baseline to 2nd week and 8th week, Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC), European Quality of Life Five Dimensions questionnaire (EQ-5D), and safety. Results. There was no significant difference between the compared indicators of the GCB and placebo groups. However, in subgroup analysis, GCB was effective for subjects with a BMI lower than 25 kg/m2. The dose of pain medication was significantly lower in the GCB group than in the placebo group after four weeks ( p = 0.016 ). There were no serious adverse events in the GCB group. Conclusions. GCB was not effective in primary outcome analysis. In exploratory subgroup analysis, GCB might be effective for individuals with BMI lower than 25 kg/m2 for the treatment of degenerative KOA. GCB may also help reduce the consumption of pain medication. Furthermore, research is required for our hypothesis. This trial is registered with KCT0003024.

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L-Carnitine supplementation ameliorates serum tumor necrosis factor-alpha and matrix metalloproteinase-3 in knee osteoarthritis women

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v12i1.30417 ◽

2017 ◽

Vol 12 (1) ◽

pp. 28 ◽

Cited By ~ 3

Author(s):

Reza Mahdavi ◽

Sousan Kolahi ◽

Vahideh Ebrahimzadeh Attari ◽

Aida Malek Mahdavi

Keyword(s):

Placebo Group ◽

Knee Osteoarthritis ◽

Global Assessment ◽

Intervention Group ◽

Controlled Study ◽

Carnitine Supplementation ◽

Double Blind ◽

Necrosis Factor Alpha ◽

Matrix Metalloproteinase 3 ◽

Significant Difference

<p class="Abstract">Seventy-two females with mild to moderate knee osteoarthritis were included in this randomized double-blind placebo-controlled study. Patients in the intervention group (n=36) received L-carnitine supplement (750 mg/day) for two months. L-Carnitine supplementation led to decrease in serum TNF-α and MMP-3 levels significantly in comparison with the baseline (p<0.001 and p<0.001, respectively) and placebo group (p<0.001 and p=0.03, respectively). In addition, physician’s global assessment of the severity of osteoarthritis decreased significantly in the L-carnitine group (p<0.001) and placebo group (p=0.012) after supplementation. At the end of the study, a significant difference was observed between the two groups for mean physician’s global assessment of the severity of osteoarthritis (p<0.001), adjusted for baseline values and duration of osteoarthritis. L-Carnitine supplementation has beneficial effects in reducing inflammatory biomarkers in knee osteoarthritis patients which subsequently leads to the alleviation of disease symptoms.</p>

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Effects of Glucosamine-Chondroitin Sulfate, Glucosamine-Chondroitin Sulfate-Methylsulfonylmethane, or Placebo in Patients with First and Second Grade of Knee Osteoarthritis

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967114s00216 ◽

2014 ◽

Vol 2 (11_suppl3) ◽

pp. 2325967114S0021

Author(s):

Erick Wonggokusuma ◽

Bambang Setyohadi ◽

Carles Siagian ◽

Andri M.T. Lubis

Keyword(s):

Placebo Group ◽

Knee Osteoarthritis ◽

Chondroitin Sulfate ◽

Womac Score ◽

Mean Difference ◽

Second Grade ◽

Controlled Clinical Trial ◽

Knee Oa ◽

Vas Score ◽

Significant Difference

Objectives: Combination of glucosamine-chondroitin sulfate is often prescribed for patients with first and second grade Kellgren-Lawrence osteoarthritis (OA). Numerous studies have reported significant efficacy of this supplement and also their combinations with methylsulfonylmethane (MSM) for the treatment of OA. However, controversies emerged regarding the effectiveness of these supplements. This current study evaluated the efficacy of glucosamine-chondroitin sulfate and glucosamine-chondroitin sulfate-MSM on improvement of patients with first and second grade knee OA. Methods: This study was a double blind, randomized controlled clinical trial on 147 patients with first and second grade (Kellgren-Lawrence) of knee OA. Subjects were allocated by permuted block randomization to three groups, either glucosamine-chondroitin sulfate (GC) (n=49), or glucosamine-chondroitin sulfate-MSM (GCM) (n=48), or placebo (n=50). The GC group received 1500 mg glucosamine + 1200 mg chondroitin sulfate + 500 mg saccharum lactis; GCM group received 1500 mg glucosamine + 1200 mg chondroitin sulfate + 500 mg MSM; while placebo group received three matching capsules of saccharum lactis. These drugs were administered once a day for three consecutive months. VAS and WOMAC score were measured at the baseline, then at 12th week after treatment. Data was analysed by using t-independent test. Results: At week 12, WOMAC score in placebo group was significantly higher than that in GCM group (mean difference 7.15, CI 12.06-2.23, p=0.005), and it was also higher in GC group compared to GCM group (mean difference 8.17, CI 13.49-2.84, p=0.003). Whereas VAS score at week 12 in placebo group was significantly higher compared to that in GC group (mean difference 0.18, CI 1.18-0.19, p=0.007) and to that in GCM group (mean difference 0.86, CI 1.37-0.35, p=0.001). However, there was no significant difference of WOMAC score at week 12 between placebo and GC groups (p=0.681), and of VAS score between GC and GCM groups (p=0.497). Conclusion: Combinations of glucosamine-chondroitin sulfate and glucosamine-chondroitin sulfate-MSM did not improve WOMAC and VAS scores in patients with grade I and II of knee osteoarthritis, when compared with placebo.

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Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

Nutrients ◽

10.3390/nu13072238 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2238

Author(s):

Xiaomei Zhang ◽

Shanbin Chen ◽

Ming Zhang ◽

Fazheng Ren ◽

Yimei Ren ◽

...

Keyword(s):

Mental Illness ◽

Placebo Group ◽

Rating Scale ◽

Controlled Trial ◽

Fermented Milk ◽

Daily Consumption ◽

Double Blind ◽

Tnf Α ◽

Significant Difference ◽

Factor Α

Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (108 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8–12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.

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Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial

Stroke and Vascular Neurology ◽

10.1136/svn-2021-000942 ◽

2021 ◽

pp. svn-2021-000942

Author(s):

Jingyi Liu ◽

Ximing Nie ◽

Hongqiu Gu ◽

Qi Zhou ◽

Haixin Sun ◽

...

Keyword(s):

Placebo Group ◽

Tranexamic Acid ◽

Intracerebral Haemorrhage ◽

Intracranial Haemorrhage ◽

Primary Outcome ◽

Controlled Trial ◽

Intracerebral Haematoma ◽

Spot Sign ◽

Double Blind ◽

Risk Of Death

BackgroundStudies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion.MethodsWe did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days.ResultsOf the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency.ConclusionsAmong patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

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Randomised Double-Blind Trial of Combination Antibiotic Therapy in Rheumatoid Arthritis

International Journal of Rheumatology ◽

10.1155/2011/585497 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Angela Smith ◽

Caroline Doré ◽

Peter Charles ◽

Alena Vallance ◽

Tara Potier ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Placebo Group ◽

Active Treatment ◽

Active Rheumatoid Arthritis ◽

Controlled Trial ◽

Primary Outcome Measure ◽

Good Evidence ◽

Double Blind ◽

Acr20 Response ◽

Significant Difference

Objective. A combination of intravenous clindamycin and oral tetracycline has been used for many years as a treatment for active rheumatoid arthritis (RA), despite the absence of good evidence for its efficacy. A single-blind pilot study of this therapy suggested that a double-blind placebo-controlled trial was warranted.Methods. Patients with active RA were randomised in a 2 : 1 ratio to receive active treatment or placebo for 25 weeks. The active treatment consisted of intravenous clindamycin in a reducing regime, and oral tetracycline twice daily three times a week. 50 patients were to be recruited. The primary outcome measure was the proportion of patients achieving an ACR20 response.Results. An interim statistical analysis was performed after 20 patients had completed the study. Two patients in the active group achieved an ACR20 response, with none in the placebo group (NS). There was a better ESR20 response in the placebo group (P=.02). There were no other significant differences between the groups. The results indicated that it was unlikely that a significant difference in ACR20 response would emerge if the remaining 30 patients were recruited. The trial was therefore halted.Conclusion. This antibiotic regime is unlikely to be a valuable therapy for active rheumatoid arthritis.

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The Effects of Propolis Extract Administration on HIV Patients Receiving ARV

The Indonesian Biomedical Journal ◽

10.18585/inabj.v13i1.1381 ◽

2021 ◽

Vol 13 (1) ◽

pp. 75-83

Author(s):

Erwin Astha Triyono ◽

Sarah Firdausa ◽

Heru Prasetyo ◽

Joni Susanto ◽

James Hutagalung ◽

...

Keyword(s):

Quality Of Life ◽

Placebo Group ◽

Clinical Symptoms ◽

Cd4 Count ◽

Controlled Clinical Trial ◽

Human Immune System ◽

Hiv Patients ◽

Double Blind ◽

Significant Difference

BACKGROUND: Human immunodeficiency virus (HIV) is an infectious disease that targets the human immune system by attacking cluster of differentiation (CD)4 cells. The use of propolis in HIV patients is expected to be safe and beneficial in terms of increasing endurance and immunity by its role in increasing CD4 level. This study aimed to analyze the influence of propolis supplementation in increasing the CD4 level in anti-retroviral (ARV)-treated HIV patients.METHODS: Double-blind randomized controlled clinical trial was conducted in 50 HIV patients who took regular ARV therapy. The subjects were divided into two groups, one group was treated with ARV and propolis, while another one was given ARV and placebo. The CD4 cell count was measured during pre-treatment, in the 3rd month, in the 6th month after treatment. The level of hemoglobin, leukocyte, and platelets were also measured. The SF-12 questionnaire was used to evaluate quality of life of the subject.RESULTS: Out of 50 subjects, 43 subjects completed the study, which were 19 subjects from the propolis group and 24 subjects from the placebo group. After 3-month of treatment, there was a statistically significant difference in the incrwase of CD 44 level in propolis group, while the increment was not significant in the placebo group. After 6-month treatment, the increase of CD4 level was occurred in both groups, propolis and placebo, however the increment was not statistically significant. The levels of hemoglobin, leukocyte, and platelets were not altered by the treatment and remained normal throughout the study. The quality of life was improved during the study; however, it was also not statistically significant. Mild adverse events occurred in 3 subjects which were relieved after the treatment stopped.CONCLUSION: Based on the result of this study, the administration of propolis on HIV patients receiving ARV bring significant difference in the increase of CD4 in propolis group from baseline to 3 month after the treatment. While in placebo group, this increment was not significant. At the end of study, CD4 count continued to rise up, however the increase was not statistically significant. There are no hemoglobin, leukocyte, platelets, and quality of life abnormalities. Therefore, it is necesary to do further research with a spesific CD4 count. However, it may be beneficial in relieving the clinical symptoms and quality of life of patient living with HIV.KEYWORDS: CD4, ARV, HIV, propolis

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Efficacy and Safety of PEGPH20 in Pancreatic Cancer: A Systematic Review and Meta-Analysis

Current Cancer Therapy Reviews ◽

10.2174/1573394717666210616152341 ◽

2021 ◽

Vol 17 ◽

Author(s):

Vinod Solipuram ◽

Harish Gopalakrishna ◽

Gayatri Naira ◽

Akhila Mohan

Keyword(s):

Pancreatic Cancer ◽

Placebo Group ◽

Febrile Neutropenia ◽

Adverse Events ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Thromboembolic Events ◽

Serious Adverse Events ◽

Significant Difference

Introduction: Pancreatic cancer is an aggressive tumor that had an estimated 57,600 new cases and 47,050 deaths in 2020 in the US alone. Recent studies have targeted tumor microenvironment (TME) for better delivery of systemic chemotherapy like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles was identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR=0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), however, there was statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there is an increased incidence of serious adverse events with the use of PEGPH20 compared to standard therapies.

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A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial for Evaluation of the Efficacy and Safety of DKB114 on Reduction of Uric Acid in Serum

Nutrients ◽

10.3390/nu12123794 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3794

Author(s):

Yu Hwa Park ◽

Do Hoon Kim ◽

Jung Suk Lee ◽

Hyun Il Jeong ◽

Kye Wan Lee ◽

...

Keyword(s):

Clinical Trial ◽

Uric Acid ◽

Placebo Group ◽

Serum Uric Acid ◽

Controlled Study ◽

Efficacy And Safety ◽

Food Ingredient ◽

Double Blind ◽

Double Blind Placebo ◽

Significant Difference

This study sought to investigate the antihyperuricemia efficacy and safety of DKB114 (a mixture of Chrysanthemum indicum Linn flower extract and Cinnamomum cassia extract) to evaluate its potential as a dietary supplement ingredient. This clinical trial was a randomized, 12-week, double-blind, placebo-controlled study. A total of 80 subjects (40 subjects with an intake of DKB114 and 40 subjects with that of placebo) who had asymptomatic hyperuricemia (7.0–9.0 mg/dL with serum uric acid) was randomly assigned. No significant difference between the DKB114 and placebo groups was observed in the amount of uric acid in serum after six weeks of intake. However, after 12 weeks of intake, the uric acid level in serum of subjects in the DKB114 group decreased by 0.58 ± 0.86 mg/dL and was 7.37 ± 0.92 mg/dL, whereas that in the placebo group decreased by 0.02 ± 0.93 mg/dL and was 7.67 ± 0.89 mg/dL, a significant difference (p = 0.0229). In the analysis of C-reactive protein (CRP) change, after 12 weeks of administration, the DKB114 group showed an increase of 0.05 ± 0.27 mg/dL (p = 0.3187), while the placebo group showed an increase of 0.10 ± 0.21 mg/dL (p = 0.0324), a statistically significant difference (p = 0.0443). In the analysis of amount of change in apoprotein B, after 12 weeks of administration, the DKB114 group decreased by 4.75 ± 16.69 mg/dL (p = 0.1175), and the placebo group increased by 3.13 ± 12.64 mg/dL (p = 0.2187), a statistically significant difference between the administration groups (p = 0.0189). In the clinical pathology test, vital signs and weight measurement, and electrocardiogram test conducted for safety evaluation, no clinically significant difference was found between the ingestion groups, confirming the safety of DKB114. Therefore, it may have potential as a treatment for hyperuricemia and gout. We suggest that DKB114 as a beneficial and safe food ingredient for individuals with high serum uric acid. Trial registration (CRIS.NIH. go. Kr): KCT0002840.

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Efficacy of Phenazone in the Treatment of Acute Migraine Attacks: A Double-Blind, Placebo-Controlled, Randomized Study

Cephalalgia ◽

10.1111/j.1468-2982.2004.00764.x ◽

2004 ◽

Vol 24 (10) ◽

pp. 888-893 ◽

Cited By ~ 15

Author(s):

H Göbel ◽

A Heinze ◽

U Niederberger ◽

T Witt ◽

V Zumbroich

Keyword(s):

Adverse Events ◽

Randomized Study ◽

Controlled Study ◽

Acute Migraine ◽

Serious Adverse Events ◽

Double Blind ◽

Double Blind Placebo ◽

Number Of Patients ◽

Significant Difference ◽

Main Target

In this study we compared the efficacy of 1000 mg phenazone with that of placebo in the treatment of acute migraine attacks in a randomized double-blind, placebo-controlled study of 208 patients. The main target criterion was the number of patients with a pain reduction from severe or moderate to slight or no pain 2 h after taking the pain medication. The percentage of patients satisfying the main target criterion was 48.6% for phenazone and 27.2% ( P < 0.05) for placebo. Freedom from pain after 2 h was reported by 27.6% with phenazone treatment and 13.6% ( P < 0.05) with placebo. Compared with placebo, the phenazone treatment also resulted in a significant improvement in the associated migraine symptoms of nausea, phonophobia and photophobia. Of patients treated with phenazone 11.4%, and 5.8% of those treated with placebo reported adverse events. There was no significant difference between the groups with regard to numbers of patients with adverse events. No serious adverse events occurred. The results show that phenazone at a dosage of 1000 mg is effective and well tolerated in the treatment of acute migraine attacks.

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Role of Anti-oxidants in the Treatment of Vitiligo

Nepal Journal of Dermatology Venereology & Leprology ◽

10.3126/njdvl.v17i1.23132 ◽

2019 ◽

Vol 17 (1) ◽

pp. 49-57

Author(s):

Amit Kumar ◽

Sudha Agrawal ◽

Tapan Kumar Dhali ◽

Shankar Kumr Majhi

Keyword(s):

Oxidative Stress ◽

Placebo Group ◽

Vitamin E ◽

Primary Outcome ◽

Antioxidant Supplementation ◽

Significant Difference ◽

Anti Oxidant ◽

And Oxidative Stress

Introduction: The role of free radicals and oxidative damage in the pathophysiology of vitiligo has been documented in recent studies. Antioxidant supplementation has been reported to be useful in the treatment of vitiligo. Objective: To evaluate the role of oral antioxidants supplementation therapy in the treatment of vitiligo by assessing the onset of repigmentation and oxidative stress. Materials and Methods: A total of 80 cases of vitiligo randomized into two groups: antioxidant and placebo comprising 40 patients each and were followed up for 8 weeks for the assessment of onset of repigmentation of vitiliginous lesions as primary outcome. The activities of Malondialdehyde (MDA), Vitamin C, and Vitamin E in serum and of Catalase (CAT) in erythrocytes of patients at baseline and at end of eight weeks were also assessed by using the spectrophotometric assay. Results: The onset of repigmentation was noted significantly earlier among the anti-oxidant group as compared to the placebo group (p=0.015). At the baseline, between the two groups, no significant difference was found in the different biochemical parameters. However, at the end of 2 months the level of MDA (p<0.001) was found to be significantly lower and that of Vitamin E (p<0.001) and CAT (p=0.005) was significantly higher among the anti-oxidants group as compared to the placebo group. Conclusion: Antioxidant supplementation carried a better response in terms of early onset of repigmentation and significant decrease in the oxidative stress, in the short follow up of two months.

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