共查询到20条相似文献,搜索用时 468 毫秒
1.
Richard N Greenberg Yadira Hurley Dinh V. Dinh Serena Mraz Javier Gomez Vera Dorothea von Bredow Alfred von Krempelhuber Siegfried Roesch Garth Virgin Nathaly Arndtz-Wiedemann Thomas Peter Meyer Darja Schmidt Richard Nichols Philip Young Paul Chaplin 《PloS one》2015,10(10)
Background
Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.Objective
This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects.Methods
Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.Results
The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.Limitations
The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.Conclusion
MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.Trial Registration
ClinicalTrials.gov NCT00316602 相似文献2.
Sharon Sheehan Stephanie A. Harris Iman Satti David A. Hokey Veerabadran Dheenadhayalan Lisa Stockdale Zita-Rose Manjaly Thomas Alice Minhinnick Morven Wilkie Samantha Vermaak Joel Meyer Matthew K. O’Shea Maria Grazia Pau Isabella Versteege Macaya Douoguih Jenny Hendriks Jerald Sadoff Bernard Landry Paul Moss Helen McShane 《PloS one》2015,10(11)
Background
MVA85A and AERAS-402 are two clinically advanced viral vectored TB vaccine candidates expressing Mycobacterium tuberculosis antigens designed to boost BCG-induced immunity. Clinical trials with candidate malaria vaccines have demonstrated that adenoviral vector based priming immunisation, followed by MVA vector boost, induced high levels of immunity. We present the safety and immunogenicity results of the first clinical trial to evaluate this immunisation strategy in TB.Methods
In this phase 1, open-label trial, 40 healthy previously BCG-vaccinated participants were enrolled into three treatment groups and vaccinated with 1 or 2 doses of AERAS-402 followed by MVA85A; or 3 doses of AERAS-402.Results
Most related adverse events (AEs) were mild and there were no vaccine related serious AEs. Boosting AERAS-402 with MVA85A significantly increased Ag85A-specific T-cell responses from day of vaccination. Two priming doses of AERAS-402 followed by MVA85A boost, resulted in a significantly higher AUC post-peak Ag85A response compared to three doses of AERAS-402 and historical data with MVA85A vaccination alone. The frequency of CD8+ T-cells producing IFN-γ, TNF-α and IL-2 was highest in the group receiving two priming doses of AERAS-402 followed by MVA85A.Conclusions
Vaccination with AERAS-402 followed by MVA85A was safe and increased the durability of antigen specific T-cell responses and the frequency and polyfunctionality of CD8+ T-cells, which may be important in protection against TB. Further clinical trials with adenoviral prime-MVA85A boost regimens are merited to optimise vaccination intervals, dose and route of immunisation and to evaluate this strategy in the target population in TB high burden countries.Trial Registration
ClinicalTrials.gov NCT01683773. 相似文献3.
Carmen Elena Gómez Beatriz Perdiguero Juan García-Arriaza Victoria Cepeda Carlos óscar Sánchez-Sorzano Beatriz Mothe José Luis Jiménez María ángeles Mu?oz-Fernández Jose M. Gatell Juan Carlos López Bernaldo de Quirós Christian Brander Felipe García Mariano Esteban 《PloS one》2015,10(11)
Trial Design
Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART.Methods
The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination.Results
MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses.Conclusion
MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity.Trial Registration
ClinicalTrials.gov NCT01571466 相似文献4.
Derek Ong Lai Teik Xiao Shiang Lee Chu Jian Lim Chia Mei Low Mariyam Muslima Luca Aquili 《PloS one》2016,11(3)
Background
There is some evidence to suggest that ginseng and Ginkgo biloba can improve cognitive performance, however, very little is known about the mechanisms associated with such improvement. Here, we tested whether cardiovascular reactivity to a task is associated with cognitive improvement.Methodology/Principal findings
Using a double-blind, placebo controlled, crossover design, participants (N = 24) received two doses of Panax Ginseng (500, 1000 mg) or Ginkgo Biloba (120, 240 mg) (N = 24), and underwent a series of cognitive tests while systolic, diastolic, and heart rate readings were taken. Ginkgo Biloba improved aspects of executive functioning (Stroop and Berg tasks) in females but not in males. Ginseng had no effect on cognition. Ginkgo biloba in females reversed the initial (i.e. placebo) increase in cardiovascular reactivity (systolic and diastolic readings increased compared to baseline) to cognitive tasks. This effect (reversal) was most notable after those tasks (Stroop and Iowa) that elicited the greatest cardiovascular reactivity during placebo. In males, although ginkgo also decreased cardiovascular readings, it did so from an initial (placebo) blunted response (i.e. decrease or no change from baseline) to cognitive tasks. Ginseng, on the contrary, increased cardiovascular readings compared to placebo.Conclusions/Significance
These results suggest that cardiovascular reactivity may be a mechanism by which ginkgo but not ginseng, in females is associated with certain forms of cognitive improvement.Trial Registration
ClinicalTrials.gov NCT02386852相似文献5.
Elizabeth A. McKie Juliet L. Reid Prafull C. Mistry Stephen L. DeWall Lee Abberley Philip D. Ambery Blas Gil-Extremera 《PloS one》2016,11(3)
Objective
Evidence suggests that chronic subclinical inflammation plays an important role in the pathogenesis of type 2 diabetes (T2DM). Circulating levels of interleukin (IL)-18 appear to be associated with a number of micro- and macrovascular comorbidities of obesity and T2DM. This study was designed to investigate whether inhibition of IL-18 had any therapeutic benefit in the treatment of T2DM. Preliminary efficacy, safety and tolerability, pharmacokinetics, and pharmacodynamics of the anti-IL-18 monoclonal antibody, GSK1070806, were assessed.Research Design and Methods
This was a multicentre, randomized, single-blind (sponsor-unblinded), placebo-controlled, parallel-group, phase IIa trial. Obese patients of either sex, aged 18–70 years, with poorly controlled T2DM on metformin monotherapy were recruited. Patients received two doses, of placebo (n = 12), GSK1070806 0.25 mg/kg (n = 13) or GSK1070806 5 mg/kg (n = 12). The primary end-point was the change from baseline in fasting plasma glucose and weighted mean glucose area under the curve (AUC)(0–4 hours) postmixed meal test on Days 29, 57, and 85.Results
Thirty-seven patients were randomized to one of the three treatment arms. There were no statistically significant effects of GSK1070806 doses on fasting plasma glucose levels, or weighted mean glucose AUC(0–4 hours) compared with placebo.Conclusions
GSK1070806 was well tolerated, and inhibition of IL-18 did not lead to any improvements in glucose control. However, because of study limitations, smaller, potentially clinically meaningful effects of IL-18 inhibition cannot be excluded.Trial Registration
ClinicalTrials.gov NCT01648153相似文献6.
Christian Daugaard Peters Krista Dybtved Kjaergaard Jens Dam Jensen Kent Lodberg Christensen Charlotte Strandhave Ida Noerager Tietze Marija Kristina Novosel Bo Martin Bibby Bente Jespersen 《PloS one》2015,10(6)
Background and Aim
Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan.Design
Randomized, double-blind, placebo-controlled, one-year intervention trial.Setting and Participants
Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year.Intervention
Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients.Outcomes and Measurements
Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension.Results
At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters.Conclusion
Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen.Trial registration
Clinicaltrials.gov NCT00791830 相似文献7.
Objective
To compare the effects of stress dose hydrocortisone therapy with placebo on survival without neurodevelopmental impairments in high-risk preterm infants.Study Design
We recruited 64 extremely low birth weight (birth weight ≤1000g) infants between the ages of 10 and 21 postnatal days who were ventilator-dependent and at high-risk for bronchopulmonary dysplasia. Infants were randomized to a tapering 7-day course of stress dose hydrocortisone or saline placebo. The primary outcome at follow-up was a composite of death, cognitive or language delay, cerebral palsy, severe hearing loss, or bilateral blindness at a corrected age of 18–22 months. Secondary outcomes included continued use of respiratory therapies and somatic growth.Results
Fifty-seven infants had adequate data for the primary outcome. Of the 28 infants randomized to hydrocortisone, 19 (68%) died or survived with impairment compared with 22 of the 29 infants (76%) assigned to placebo (relative risk: 0.83; 95% CI, 0.61 to 1.14). The rates of death for those in the hydrocortisone and placebo groups were 31% and 41%, respectively (P = 0.42). Randomization to hydrocortisone also did not significantly affect the frequency of supplemental oxygen use, positive airway pressure support, or need for respiratory medications.Conclusions
In high-risk extremely low birth weight infants, stress dose hydrocortisone therapy after 10 days of age had no statistically significant effect on the incidence of death or neurodevelopmental impairment at 18–22 months. These results may inform the design and conduct of future clinical trials.Trial Registration
ClinicalTrials.gov NCT00167544 相似文献8.
Alice B. Gottlieb James G. Krueger Mia Sandberg Lundblad Marie G?thberg Brett E. Skolnick 《PloS one》2015,10(8)
Background
The current trial was a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the recombinant monoclonal anti−interleukin-20 (IL-20) antibody, NNC0109-0012, which targets the inflammatory cytokine IL-20.Methods
In total, 48 patients aged 18 to 75 years with moderate to severe stable chronic plaque psoriasis with affected body surface area ≥15% and physician global assessment score ≥3 were enrolled in this randomized, double-blind, multicenter, placebo-controlled, phase 1 dose-escalation trial. Patients were randomized within each single dose cohort (0.01, 0.05, 0.2, 0.6, 1.5, or 3.0 mg/kg) or multiple dose cohort (0.05, 0.2, 0.5, 1.0, or 2.0 mg/kg; 1 dose every other week for 7 weeks) of NNC0109-0012 or placebo in a 3:1 ratio. In the expansion phase, 7 patients were randomized to weekly doses of 2.0 mg/kg NNC0109-0012 or placebo for 7 weeks. The primary objective, safety and tolerability, was assessed by evaluating adverse events (AEs). Additional endpoints included pharmacokinetics, pharmacodynamics, and clinical response (assessed using the Psoriasis Area and Severity Index [PASI] score).Results
AEs were reported in 85% of patients (n = 40) in the initial study phases (NNC0109-0012, 83%; placebo, 92%) and in 4 of 7 patients in the multiple-dose expansion phase. One serious AE was reported but was judged not to be causally related to NNC0109-0012. No dose-limiting toxicities were reported. NNC0109-0012 pharmacokinetics was similar to other monoclonal antibodies, with an average half-life of approximately 3 weeks. There was a dose-proportional increase in area under the curve and maximum concentration after single dosing. No substantial changes in pharmacodynamic parameters were observed. The expansion phase was terminated early due to apparent lack of PASI improvement.Conclusion
Single and multiple doses of NNC0109-0012, ranging from 0.05 to 3.0 mg/kg, were well tolerated in patients with psoriasis and exhibited pharmacokinetics similar to that of other monoclonal antibodies.Trial Registration
ClinicalTrials.gov NCT01261767 相似文献9.
Christa Kasang Samuel Kalluvya Charles Majinge Gilbert Kongola Mathias Mlewa Irene Massawe Rogatus Kabyemera Kinanga Magambo Albrecht Ulmer Hartwig Klinker Eva Gschmack Anne Horn Eleni Koutsilieri Wolfgang Preiser Daniela Hofmann Johannes Hain Andreas Müller Lars D?lken Benedikt Weissbrich Axel Rethwilm August Stich Carsten Scheller 《PloS one》2016,11(1)
Background
HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients.Methods
Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov ). Inclusion criteria were a CD4 count above 300 cells/μl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/μl. NCT01299948Results
No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/μl compared to -37.42 ± 10.77 cells/μl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men.Conclusions
This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection.Trial Registration
ClinicalTrials.gov NCT01299948相似文献10.
Usha Ramakrishnan Amanda Stinger Ann M. DiGirolamo Reynaldo Martorell Lynnette M. Neufeld Juan A. Rivera Lourdes Schnaas Aryeh D. Stein Meng Wang 《PloS one》2015,10(8)
Objective
We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age.Design
Randomized placebo double-blind controlled trial.Settings
Cuernavaca, Mexico.Participants and Methods
We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment.Interventions or Main Exposures
400 mg/day of algal DHA.Outcome Measures
Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores.Results
Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation.Conclusions
Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments.Trial Registration
Clinicaltrials.gov NCT00646360 相似文献11.
Anna P. Ralph Govert Waramori Gysje J. Pontororing Enny Kenangalem Andri Wiguna Emiliana Tjitra Sandjaja Dina B. Lolong Tsin W. Yeo Mark D. Chatfield Retno K. Soemanto Ivan Bastian Richard Lumb Graeme P. Maguire John Eisman Ric N. Price Peter S. Morris Paul M. Kelly Nicholas M. Anstey 《PloS one》2013,8(8)
Background
Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB).Methods
In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov . NCT00677339Results
200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference −3%, 95% CI −19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI −9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes.Conclusion
Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes.Registry
ClinicalTrials.gov. Registry number: NCT00677339相似文献12.
Brechje de Gier Maiza Campos Ponce Marlene Perignon Marion Fiorentino Kuong Khov Chhoun Chamnan Michiel R. de Boer Megan E. Parker Kurt Burja Marjoleine A. Dijkhuizen Jacques Berger Katja Polman Frank T. Wieringa 《PloS one》2016,11(1)
Background
Fortification of staple foods is considered an effective and safe strategy to combat micronutrient deficiencies, thereby improving health. While improving micronutrient status might be expected to have positive effects on immunity, some studies have reported increases in infections or inflammation after iron supplementation.Objective
To study effects of micronutrient-fortified rice on hookworm infection in Cambodian schoolchildren.Methods
A double-blinded, cluster-randomized trial was conducted in 16 Cambodian primary schools partaking in the World Food Program school meal program. Three types of multi-micronutrient fortified rice were tested against placebo rice within the school meal program: UltraRice_original, UltraRice_improved and NutriRice. Four schools were randomly assigned to each study group (placebo n = 492, UltraRice_original n = 479, UltraRice_improved n = 500, NutriRice n = 506). Intestinal parasite infection was measured in fecal samples by Kato-Katz method at baseline and after three and seven months. In a subgroup (N = 330), fecal calprotectin was measured by ELISA as a marker for intestinal inflammation.Results
Baseline prevalence of hookworm infection was 18.6%, but differed considerably among schools (range 0%- 48.1%).Micronutrient-fortified rice significantly increased risk of new hookworm infection. This effect was modified by baseline hookworm prevalence at the school; hookworm infection risk was increased by all three types of fortified rice in schools where baseline prevalence was high (>15%), and only by UltraRice_original in schools with low baseline prevalence. Neither hookworm infection nor fortified rice was related to fecal calprotectin.Conclusions
Consumption of rice fortified with micronutrients can increase hookworm prevalence, especially in environments with high infection pressure. When considering fortification of staple foods, a careful risk-benefit analysis is warranted, taking into account severity of micronutrient deficiencies and local prevalence of parasitic infections.Trial Registration
ClinicalTrials.gov NCT01706419相似文献13.
Background
Improving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI).Methods
Forty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal.Results
Changes in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures).Conclusion
Our results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted.Trial Registration
ClinicalTrials.gov NCT02091635 相似文献14.
Zoe Moodie Barbara Metch Linda-Gail Bekker Gavin Churchyard Maphoshane Nchabeleng Koleka Mlisana Fatima Laher Surita Roux Kathryn Mngadi Craig Innes Matsontso Mathebula Mary Allen Carter Bentley Peter B. Gilbert Michael Robertson James Kublin Lawrence Corey Glenda E. Gray 《PloS one》2015,10(9)
Background
The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study.Methods
HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models.Results
Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08–2.15, p = 0.02, 82 vaccine/54 placebo infections). The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001) but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62).Conclusion
The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women.Trial Registration
clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539 相似文献15.
Trevor W. R. Lee Stephen Kowalski Kelsey Falk Doug Maguire Darren H. Freed Kent T. HayGlass 《PloS one》2016,11(3)
Background
Cardiac surgery induces many physiologic changes including major inflammatory and sympathetic nervous system responses. Here, we conducted a single-centre pilot study to generate hypotheses on the potential immune impact of adding high spinal anaesthesia to general anaesthesia during cardiac surgery in adults. We hypothesized that this strategy, previously shown to blunt the sympathetic response and improve pain management, could reduce the undesirable systemic inflammatory responses caused by cardiac surgery.Methods
This prospective randomized unblinded pilot study was conducted on 14 patients undergoing cardiac surgery for coronary artery bypass grafting and/or aortic valve replacement secondary to severe aortic stenosis. The primary outcome measures examined longitudinally were serum pro-inflammatory (IL-6, IL-1b, CCL2), anti-inflammatory (IL-10, TNF-RII, IL-1Ra), acute phase protein (CRP, PTX3) and cardiovascular risk (sST2) biomarkers.Results
The kinetics of pro- and anti-inflammatory biomarker was determined following surgery. All pro-inflammatory and acute phase reactant biomarker responses induced by surgical stress were indistinguishable in intensity and duration between control groups and those who also received high spinal anaesthesia. Conversely, IL-10 levels were markedly elevated in both intensity and duration in the group receiving high spinal anesthesia (p = 0.005).Conclusions
This hypothesis generating pilot study suggests that high spinal anesthesia can alter the net inflammatory response that results from cardiac surgery. In appropriately selected populations, this may add incremental benefit by dampening the net systemic inflammatory response during the week following surgery. Larger population studies, powered to assess immune, physiologic and clinical outcomes in both acute and longer term settings, will be required to better assess potential benefits of incorporating high spinal anesthesia.Trial Registration
ClinicalTrials.gov NCT00348920相似文献16.
Leah M. Feazel Stephanie A. Santorico Charles E. Robertson Mahfudh Bashraheil J. Anthony G. Scott Daniel N. Frank Laura L. Hammitt 《PloS one》2015,10(6)
Objective
Pneumococcal conjugate vaccines reduce the prevalence of vaccine serotypes carried in the nasopharynx. Because this could alter carriage of other potential pathogens, we assessed the nasopharyngeal microbiome of children who had been vaccinated with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV).Methods
Profiles of the nasopharyngeal microbiota of 60 children aged 12-59 months, who had been randomized to receive 2 doses of PHiD-CV (n=30) or Hepatitis A vaccine (n=30) 60 days apart, were constructed by 16S rRNA gene pyrosequencing of swab specimens collected before vaccination and 180 days after dose 1.Results
Prior to vaccination, Moraxella catarrhalis (median of 12.3% of sequences/subject), Streptococcus pneumoniae (4.4%) and Corynebacterium spp. (5.6%) were the most abundant nasopharyngeal bacterial species. Vaccination with PHiD-CV did not significantly alter the species composition, abundance, or prevalence of known pathogens. Distinct microbiomes were identified based on the abundances of Streptococcus, Moraxella, and Haemophilus species. These microbiomes shifted in composition over the study period and were independent of age, sex, school attendance, antibiotic exposure, and vaccination.Conclusions
Vaccination of children with two doses of PHiD-CV did not significantly alter the nasopharyngeal microbiome. This suggests limited replacement carriage with pathogens other than non-vaccine strains of S. pneumoniae.Trial Registration
clinicaltrials.gov NCT01028326 相似文献17.
Jorge Duconge Alga S. Ramos Karla Claudio-Campos Giselle Rivera-Miranda Luis Bermúdez-Bosch Jessicca Y. Renta Carmen L. Cadilla Iadelisse Cruz Juan F. Feliu Cunegundo Vergara Gualberto Rua?o 《PloS one》2016,11(1)
Aim
This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients.Patients & Methods
A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals.Results
The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias).Conclusions
Results supported our rationale to incorporate individual’s genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics.Trial Registration
ClinicalTrials.gov NCT01318057相似文献18.
Sonia Gaucher Isabelle Boutron Florence Marchand-Maillet Gabriel Baron Richard Douard Jean-Pierre Béthoux AMBUPROG Group Investigators 《PloS one》2016,11(2)
Objectives
To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial).Design
Multicenter, two-arm, parallel-group, open-label randomized controlled trial.Setting
11 university hospital ambulatory surgery units in Paris, France.Participants
Patients scheduled for ambulatory surgery and able to be reached by telephone.Intervention
A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults), was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone.Main Outcome Measures
Rate of cancellation on the day of surgery or the day before.Results
The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6%) vs. 113 (5.8%), adjusted odds ratio [95% confidence interval] = 0.91 [0.65–1.29], (p = 0.57)). Checklist administration revealed that 355 patients (28.0%) had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0%) still had questions concerning the fasting state.Conclusions
A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes.Trial Registration
ClinicalTrials.gov NCT01732159相似文献19.
Cristina Lopes Jose Soares Freni Tavaria Ana Duarte Osvaldo Correia Oksana Sokhatska Milton Severo Diana Silva Manuela Pintado Luis Delgado Andre Moreira 《PloS one》2015,10(11)
Background
Atopic dermatitis (AD) patients may benefit from using textiles coated with skin microbiome–modulating compounds. Chitosan, a natural biopolymer with immunomodulatory and antimicrobial properties, has been considered potentially useful.Objective
This randomized controlled trial assessed the clinical utility of chitosan-coated garment use in AD.Methods
Of the 102 patients screened, 78 adult and adolescents were randomly allocated to overnight use of chitosan-coated or uncoated cotton long-sleeved pyjama tops and pants for 8 weeks. The primary outcome was change in disease severity assessed by Scoring Atopic dermatitis index (SCORAD). Other outcomes were changes in quality of life, pruritus and sleep loss, days with need for rescue medication, number of flares and controlled weeks, and adverse events. Changes in total staphylococci and Staphylococcus aureus skin counts were also assessed. Comparisons were made using analysis of variance supplemented by repeated measures analysis for the primary outcome. Interaction term between time and intervention was used to compare time trends between groups.Results
Chitosan group improved SCORAD from baseline in 43.8%, (95%CI: 30.9 to 55.9), P = 0.01, placebo group in 16.5% (-21.6 to 54.6); P = 0.02 with no significant differences between groups; Dermatology Quality of life Index Score significantly improved in chitosan group (P = 0.02) and a significant increase of skin Coagulase negative Staphylococci (P = 0.02) was seen.Conclusions
Chitosan coated textiles may impact on disease severity by modulating skin staphylococcal profile. Moreover, a potential effect in quality of life may be considered.Trial Registration
ClinicalTrials.gov NCT01597817相似文献20.
Juliet Mpendo Gaudensia Mutua Julien Nyombayire Rosine Ingabire Annet Nanvubya Omu Anzala Etienne Karita Peter Hayes Jakub Kopycinski Len Dally Drew Hannaman Michael A. Egan John H. Eldridge Kristen Syvertsen Jennifer Lehrman Beth Rasmussen Jill Gilmour Josephine H. Cox Patricia E. Fast Claudia Schmidt 《PloS one》2015,10(8)