Dataset Information

Biocurcumin as Radiosensitiser for Cervical Cancer Study (BRACES): A Double-Blind Randomised Placebo-Controlled Trial.

ABSTRACT: Cervical cancer is a leading cause of death among women worldwide, particularly in Indonesia. The main treatment of advanced-stage cervical cancer is radiation; however, the outcomes do not meet the required expectations. [1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione] has been reported in several studies for its potency in cancer therapy. This study aims to investigate the clinical and molecular [(malondialdehyde (MDA) and NF-?B levels] effects, apoptotic index, and safety of Biocurcumin (BCM-95) as a radiosensitiser in cervical cancer. In this double-blind placebo randomised-controlled trial, we randomised 121 patients into 2 groups (BCM-95 or placebo). MDA and their NF-?B levels and apoptotic index were measured before and after administering 24?Gy of radiation. MDA was identified using Wills' method, whereas NF-?B was identified via ELISA. The apoptotic index was identified using TUNEL and DAPI staining. The clinical response was classified based on the RECIST. MDA levels before radiation were similar between both groups in per protocol and intention-to-treat (ITT) analyses (p = 0.53 and p = 0.16, respectively). After radiation, MDA levels increased in both groups with no significant differences in per protocol and ITT analyses (p = 0.52 and p = 0.18, respectively). NF-?B levels before radiation were similar between the two groups in per protocol and ITT analyses (p = 0.92 and p = 0.98, respectively). After radiation, the BCM-95 group showed an increase in the NF-?B levels compared with the placebo group in per protocol analysis but not in ITT analysis (p = 0.018 and p = 0.42, respectively). The BCM-95 group had a higher apoptotic index before radiation in per protocol analysis but not in ITT analysis (p = 0.01 and p = 0.61, respectively). After radiation, the apoptotic index remained higher in the BCM-95 group in per protocol analysis but not in ITT analysis (p = 0.04 and p = 0.91, respectively). There was no significant difference in complete response between the groups (per protocol, p = 0.61; ITT analysis, p = 0.90). Although BCM-95 can regulate ROS, NF-?B, and apoptosis in human cervical cancer, it is not significant. Therefore, BCM-95 does not improve clinical response to radiation treatment.

SUBMITTER: Purbadi S

PROVIDER: S-EPMC7275233 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Biocurcumin as Radiosensitiser for Cervical Cancer Study (BRACES): A Double-Blind Randomised Placebo-Controlled Trial.

Purbadi Sigit S Rustamadji Primariadewi P Prijanti Ani R AR Sekarutami Sri M SM Sutrisna Bambang B Suyatna Franciscus D FD Andrijono

Evidence-based complementary and alternative medicine : eCAM 20200528

Cervical cancer is a leading cause of death among women worldwide, particularly in Indonesia. The main treatment of advanced-stage cervical cancer is radiation; however, the outcomes do not meet the required expectations. [1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione] has been reported in several studies for its potency in cancer therapy. This study aims to investigate the clinical and molecular [(malondialdehyde (MDA) and NF-<i>κ</i>B levels] effects, apoptotic index, and safety o ...[more]

PMID: 32565848

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Project description:ObjectiveTo assess the efficacy and safety of varenicline (a licensed cigarette smoking cessation aid) in helping users of smokeless tobacco to quit.DesignDouble blind, placebo controlled, parallel group, multicentre, randomised controlled trial.SettingMedical clinics (mostly primary care) in Norway and Sweden.ParticipantsMen and women aged ≥18 who used smokeless tobacco at least eight times a day, with no abstinence period over three months within one year before screening, who wanted to quit all tobacco use. Participants were excluded if they used any other form of tobacco (except smokeless tobacco) or medication to stop smoking within three months of screening or had any pre-existing medical or psychiatric condition.InterventionsVarenicline 1 mg twice daily (titrated during the first week) or placebo for 12 weeks, with 14 weeks' follow-up after treatment.Main outcome measuresThe primary end point was the four week continuous abstinence rate at the end of treatment (weeks 9-12) confirmed with cotinine concentration. A secondary end point was continuous abstinence rate for weeks 9-26. Safety and tolerability were also evaluated.Results431 participants (213 varenicline; 218 placebo) were randomised and received at least one dose of study drug. Participants' demographics and baseline use of smokeless tobacco were similar (89% (189) and 90% (196), respectively, were men; mean age in both groups was 43.9; participants used smokeless tobacco products about 15 times a day, and about 80% first used smokeless tobacco within 30 minutes after awakening). Continuous abstinence rate at week 9-12 was higher in the varenicline group than the placebo group (59% (125) v 39% (85); relative risk 1.60, 95% confidence interval 1.32 to 1.87, P<0.001; risk difference 20%; number needed to treat 5). The advantage of varenicline over placebo persisted through 14 weeks of follow-up (continuous abstinence rate at week 9-26 was 45% (95) v 34% (73); relative risk 1.42, 1.08 to 1.79, P=0.012; risk difference 11%; number needed to treat 9). The most common adverse events in the varenicline group compared with the placebo group were nausea (35% (74) v 6% (14)), fatigue (10% (22) v 7% (15)), headache (10% (22) v 9% (20)), and sleep disorder (10% (22) v 7% (15)). Few adverse events led to discontinuation of treatment (9% (19) and 4% (9), respectively), and serious adverse events occurred in two (1%) and three (1%) participants, respectively.ConclusionVarenicline can help people to give up smokeless tobacco and has an acceptable safety profile. The response rate in the placebo group in this study was high, suggesting a population less resistant to treatment than smokers.Trial registrationNCT00717093.

Project description:BackgroundTuberous Sclerosis Complex (TSC) is a genetic disorder characterised by the development of benign tumours secondary to loss of inhibitory regulation of the mTOR (mechanistic Target of Rapamycin) intracellular growth pathway. Metformin inhibits the mTOR pathway. We investigated whether metformin would reduce growth of hamartomas associated with tuberous sclerosis complex.MethodsIn this multicentre randomized, double-blind, placebo-controlled trial, patients with a clinical diagnosis of tuberous sclerosis, aged over 10 years and with at least one renal angiomyolipoma of greater than 1 cm in diameter were enrolled. Participants were randomly allocated (1:1) by a secure website to receive metformin or placebo for 12 months. The primary outcome was percentage volume change of renal angiomyolipomas (AML) at 12 months compared to baseline. Secondary outcomes were percentage change at 12 months from baseline in volume of cerebral Subependymal Giant Cell Astrocytomas (SEGA); appearance of facial and ungual hamartomas; frequency of epileptic seizures; and adaptive behaviour. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 92545532, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2011-001319-30.FindingsBetween 1 November 2012 and 30 September 2015 72 patients were screened and 55 were randomly assigned to metformin (28) or placebo (27). Four participants withdrew between randomisation and starting treatment. All 51 patients who started therapy completed the trial and were assessed for outcome at 12 months. The median percentage change in angiomyolipoma (AML) volume was +7.6% (IQR -1.8% to +42.6%) for the placebo group and +8.9% (IQR 1.3% to 19.5%) for the metformin group (p = 0.28). Twenty-seven patients had SEGAs: 13 received placebo and 14 metformin. The median percentage change in SEGA volume was +3.0% (IQR -22.8% to +27.7%) for the placebo group and - 20.8% (IQR - 47.1% to - 5.0%) for the metformin group (p = 0.03). Twenty-one patients were assessed for seizure frequency: 9 received placebo and 12 received metformin. In the metformin group, a mean reduction of 43.7% from baseline in seizures was observed and in the placebo group a 3.1% mean reduction was observed, with a difference in response of 40.6% (95% CI -3.1% to +84.2%, p = 0.03). There were no significant differences between metformin and placebo groups for the other secondary outcomes. There were no deaths. Three serious adverse events (SAEs) occurred during the trial (all patients on metformin).InterpretationMetformin did not reduce AML volume. Metformin did reduce SEGA volume and seizure frequency compared with placebo. There may be a role for metformin in slowing or reversing growth of some life-threatening hamartomas in TSC and for reducing seizure frequency. Further study is justified.FundingThis study was funded by the National Institute for Health and Research (NIHR) through the The Research for Patient Benefit Programme (RfPB).

Project description:IntroductionSepsis is a major cause of death among hospitalised patients. Accumulating evidence suggests that immune response during sepsis cascade lies within a spectrum of dysregulated host responses. On the one side of the spectrum there are patients whose response is characterised by fulminant hyperinflammation or macrophage activation-like syndrome (MALS), and on the other side patients whose immune response is characterised by immunoparalysis. A sizeable group of patients are situated between the two extremes. Recognising immune endotype is very important in order to choose the appropriate immunotherapeutic approach for each patient resulting in the best chance to improve the outcome.Methods and analysisImmunoSep is a randomised placebo-controlled phase 2 clinical trial with a double-dummy design in which the effect of precision immunotherapy on sepsis phenotypes with MALS and immunoparalysis is studied. Patients are stratified using biomarkers. Specifically, 280 patients will be 1:1 randomly assigned to placebo or active immunotherapy as adjunct to standard-of-care treatment. In the active immunotherapy arm, patients with MALS will receive anakinra (recombinant interleukin-1 receptor antagonist) intravenously, and patients with immunoparalysis will receive subcutaneous recombinant human interferon-gamma. Τhe primary endpoint is the comparative decrease of the mean total Sequential Organ Failure Assessment score by at least 1.4 points by day 9 from randomisation.Ethics and disseminationThe protocol is approved by the German Federal Institute for Drugs and Medical Devices; the National Ethics Committee of Greece and by the National Organization for Medicines of Greece; the Central Committee on Research Involving Human Subjects and METC Oost Netherland for the Netherlands; the National Agency for Medicine and Medical Products of Romania; and the Commission Cantonale d'éthique de la recherche sur l'être human of Switzerland. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04990232.

Project description:BackgroundIrbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome.MethodsWe did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794.FindingsBetween March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events.InterpretationIrbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications.FundingBritish Heart Foundation, the UK Marfan Trust, the UK Marfan Association.

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Dataset Information

Biocurcumin as Radiosensitiser for Cervical Cancer Study (BRACES): A Double-Blind Randomised Placebo-Controlled Trial.

Publications

Biocurcumin as Radiosensitiser for Cervical Cancer Study (BRACES): A Double-Blind Randomised Placebo-Controlled Trial.

Similar Datasets

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