ABSTRACT: 16S rRNA sequencing of baseline sputum from international, randomised, double-blind, placebo-controlled, phase 3 trials of liposomal ciprofloxacin in patients with bronchiectasis
Project description:Comparison between pretreated donor grafts corticosteroid vs. placebo Prospective, randomised, double-blind, placebo-control trial, xls files contain normalized data (Default Total Intensity Normalization, see Stanford Microarray Database website), gpr files the raw data
Project description:Long-term, low dose azithromycin reduces exacerbation frequency in COPD yet the mechanism remains unclear. This study characterises changes to gene expression in patients with neutrophilic COPD in response to long term low dose azithromycin therapy. Patients with neutrophilic COPD (>61% or >162x10^4/mL sputum neutrophils) were randomised to 12 weeks of either azithromycin or placebo treatment. RNA was extracted from sputum and blood collected before (pre) and after (post) treatment.
Project description:The aim of the experiment was to assign patients enrolled in the VANISH randomised trial to sepsis response signature (SRS) endotypes based on a previously published gene expression signature, in order to test for differential responses to treatment. VANISH was a double-blind randomised clinical trial in septic shock, with patients randomised to receive norepinephrine or vasopressin followed by hydrocortisone or placebo. We collected blood samples upon enrolment, extracted RNA and performed transcriptomic profiling using microarrays, allocated patients to SRS1 or SRS2 using a linear model (Davenport 2016), and tested for an association between sepsis endotype and response to either norepinephrine or vasopressin, or to corticosteroids. There was a significant interaction between treatment with hydrocortisone or placebo, and SRS endotype (p=0·02)
Project description:Some commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-κB-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli. Keywords: mucosal response of healthy adult humans to lactic acid bacteria This study was set up according to a randomised double-blind cross-over placebo-controlled design. It contains transcriptional profiles from biopsies from 8 healthy individuals after oral intake of three different growth stages of Lactobacillus plantarum or placebo control. In total, this study includes data from 8 individuals x 4 treatments=32 arrays.
Project description:There is an urgent unmet need in solid organ transplantation for immunotherapeutic strategies that target B cells and plasma cells, ideally without increasing infectious complications. We conducted a phase 2 double-blind randomised placebo-controlled trial to assess the safety and potential efficacy of an anti-BLyS antibody, belimumab, in addition to standard of care immunosuppression post-kidney transplantation.
Project description:Canakinumab is a human anti-interleukin-1 beta (IL-1 beta) monoclonal antibody neutralizing IL-1 beta. Systemic juvenile idiopathic arthritis (SJIA) is a rare, multigenic, autoinflammatory disease of unknown etiology characterized by chronic arthritis; intermittent high-spiking fever, rash, and elevated levels of acute-phase reactants. Blood samples of SJIA patients were obtained from two phase 3 clinical trials conducted by the members of the Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG) (Clinicaltrials.gov: NCT00886769 and NCT00889863). For patients, baseline and day 3 samples were analyzed for either placebo or canakinumab (Ilaris) treatment. Clinical response was assessed at day 15 using adapted JIA American College of Rheumatology (ACR) response criteria. Overall, 206 samples were used in this study including 22 samples from healthy controls, 33 samples of placebo treated patients and 151 samples of canakinumab treated patients.
Project description:Interleukin (IL)-23 is implicated in T2 and T17-mediated airway inflammation, supporting a role in asthma. We undertook a Phase II, randomized, double-blind, placebo-controlled, 24-week, parallel-group, multicenter trial to assess the efficacy and safety of risankizumab, an IL23p19 monoclonal antibody, administered subcutaneously (90 mg 4 weekly) in adults with severe asthma. Sputum samples were collected at several timepoints: visit 1B (week -3), visit 2 (week 0 proir to treatment), visit 7 (week 20), visit 8 (week 24, end of treatment), visit 12 (week 40, end of observation). RNA sequencing of sputum cells.
Project description:Canakinumab is a human anti-interleukin-1 beta (IL-1 beta) monoclonal antibody neutralizing IL-1 beta. Systemic juvenile idiopathic arthritis (SJIA) is a rare, multigenic, autoinflammatory disease of unknown etiology characterized by chronic arthritis; intermittent high-spiking fever, rash, and elevated levels of acute-phase reactants. Blood samples of SJIA patients were obtained from two phase 3 clinical trials conducted by the members of the Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG) (Clinicaltrials.gov: NCT00886769 and NCT00889863). For patients, baseline and day 3 samples were analyzed for either placebo or canakinumab (Ilaris) treatment. Clinical response was assessed at day 15 using adapted JIA American College of Rheumatology (ACR) response criteria.
Project description:Background: We tested the hypothesis that short-term supplementation with a physiological dose of folate can alter global gene expression in the colon of subjects with colorectal adenoma using a randomised double blind placebo controlled trial design. Materials and Methods: Fourteen subjects with histologically confirmed colorectal adenoma, randomised to receive folic acid (400M-BM-5g/d, n=6) or placebo (n=8) for 10 weeks, had blood samples and colonic tissue biopsies collected before and after the intervention. Blood samples were used to determine serum and red cell folate, plasma homocysteine, and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase (MS A2756G). RNA extracted from normal-appearing colonic tissue samples was used to determine global gene expression in the colon using AffymetrixM-oM-^CM-^R Microarray GeneChips. Microarray results were confirmed by quantitative real time RT-PCR. Two methods were used to analyse the microarray data: (1) differences between pre- and post-intervention gene expression values in the folic acid and placebo groups separately using paired-sample t tests; (2) differences between the folic acid and placebo groups in the ratio of post-intervention to pre-intervention gene expression values using independent sample t-tests. Results: (1) Following intervention, sixty seven genes were up-regulated and 13 genes were down-regulated in the folic acid group, while 21 genes were up-regulated and none were down-regulated in the placebo group (P<0.05, adjusted for multiple testing). (2) Thirty six genes were up-regulated and 18 genes were down-regulated in the folic acid group when compared with placebo, but none of these were statistically significant after adjustment for multiple testing. These genes are involved in multiple pathways, including cell cycle, signal transduction, cell differentiation, transport, cell division, cell motility, protein transport and immune response. There were no genes involved in 1-carbon metabolism that were altered in expression, although several genes involved in neoplasia were up-regulated. Conclusions: These results indicate that while folic acid can modify gene expression, it is difficult to separate its effects from the natural variability in gene expression in the colon. Fourteen patients with colorectal adenoma were treated with either folate supplementation (6 subjects) or a placebo (8 subjects) for 10 weeks in a randomised double-blind trial. Colonic biopsies of normal tissue were taken before and after the intervention, and analysed for gene expression.
Project description:Glucose-dependent insulinotropic polypeptide (GIP) has been proposed to exert insulin-independent effects on lipid and bone metabolism. We investigated the effect of a 6-day s.c. GIP infusion on circulating lipids, white adipose tissue (WAT), brown adipose tissue (BAT), hepatic fat content, and inflammatory markers in patients with type 1 diabetes. In a randomized, placebo-controlled, double-blind, crossover study, 20 men with type 1 diabetes underwent a 6-day continuous s.c. infusion with GIP (6 pmol/kg/min) and placebo (saline), with an interposed seven-day washout period. Each intervention period involved three study days: Day 0 (baseline measurements, a baseline abdominal adipose tissue biopsy and blood sampling), Day 1 (fasting blood sample after 24 hours infusion), and Day 6 (fasting blood sample, an abdominal adipose tissue biopsy).