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1.
Young Eun Kim Ji Young Yun Hui June Yang Han-Joon Kim Namyi Gu Seo Hyun Yoon Joo-Youn Cho Beom S. Jeon 《PloS one》2012,7(11)
Background
Freezing of gait (FOG) is one of the most disabling symptoms in Parkinsonism. Open-label studies have suggested that intravenous (IV) amantadine is effective against FOG resistant to dopaminergic therapy in Parkinson''s disease (PD). We evaluated the efficacy of IV amantadine on FOG resistant to dopaminergic therapy.Methodology/Principal Findings
This was a randomized, double-blind, placebo-controlled, cross-over study on IV amantadine. The placebo (normal saline) and amantadine (400 mg/day) were injected for 2 days with a 52-hour washout period. The instruments for the outcome measures were the Freezing of Gait Questionnaire (FOGQ), Unified Parkinson''s disease rating Scale (UPDRS), and the duration of the 4×10 m walking test. The placebo arm was compared to the amantadine arm. Ten patients were enrolled but two patients withdrew, one from each arm. The FOGQ and UPDRS scores and the duration of the 4×10 m walking test improved in both arms compared to the baseline (P<0.05 in all). However, there were no differences in these values between the amantadine arm and placebo arm (P = 0.368, P = 0.583, P = 0.206, respectively). Follow-up measures 2weeks after discharge in an open-label study showed the beneficial effects of an amantadine tablet on FOG (FOGQ, P = 0.018; UPDRS, P = 0.012 respectively).Conclusions/Significance
This double blind, placebo-controlled study did not show the efficacy of IV amantadine on FOG when compared with the placebo. This study provides Class II evidence due to small sample size for the lack of benefit of IV amantadine on FOG resistant to dopaminergic therapyTrial Registration
Clinicaltrials.gov NCT01313819相似文献2.
Mayu O. Frank Julia Kaufman Suyan Tian Mayte Suárez-Fari?as Salina Parveen Nathalie E. Blachère Michael J. Morris Susan Slovin Howard I. Scher Matthew L. Albert Robert B. Darnell 《PloS one》2010,5(9)
Background
Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine.Methods and Findings
We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination.Conclusions
An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine. (ClinicalTrials.gov number ). NCT00289341Trial Registration
ClinicalTrials.gov NCT00289341相似文献3.
Marina Chiara Garassino Sheila Piva Nicla La Verde Ilaria Spagnoletti Vittorio Iorno Claudia Carbone Antonio Febbraro Anna Bianchi Annalisa Bramati Anna Moretti Monica Ganzinelli Mirko Marabese Marta Gentili Valter Torri Gabriella Farina 《PloS one》2013,8(4)
Purpose
Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy.Methods
Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%.Results
More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%.Conclusions
Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control.Trial Registration
ClinicalTrials.gov NCT00637975相似文献4.
Mahamadou S. Sissoko Abdoulaye Dabo Hamidou Traoré Mouctar Diallo Boubacar Traoré Drissa Konaté Boubacar Niaré Moussa Diakité Bourama Kamaté Abdrahamane Traoré Aboudramane Bathily Amadou Tapily Ousmane B. Touré Sarah Cauwenbergh Herwig F. Jansen Ogobara K. Doumbo 《PloS one》2009,4(10)
Background
This study was conducted to determine the efficacy of the antimalarial artemisinin-based combination therapy (ACT) artesunate +sulfamethoxypyrazine/pyrimethamine (As+SMP), administered in doses used for malaria, to treat Schistosoma haematobium in school aged children.Methodology/Principal Findings
The study was conducted in Djalakorodji, a peri-urban area of Bamako, Mali, using a double blind setup in which As+SMP was compared with praziquantel (PZQ). Urine samples were examined for Schistosoma haematobium on days −1, 0, 28 and 29. Detection of haematuria, and haematological and biochemical exams were conducted on day 0 and day 28. Clinical exams were performed on days 0, 1, 2, and 28. A total of 800 children were included in the trial. The cure rate obtained without viability testing was 43.9% in the As+SMP group versus 53% in the PZQ group (Chi2 = 6.44, p = 0.011). Egg reduction rates were 95.6% with PZQ in comparison with 92.8% with As+SMP, p = 0.096. The proportion of participants who experienced adverse events related to the medication was 0.5% (2/400) in As+SMP treated children compared to 2.3% (9/399) in the PZQ group (p = 0.033). Abdominal pain and vomiting were the most frequent adverse events in both treatment arms. All adverse events were categorized as mild.Conclusions/Significance
The study demonstrates that PZQ was more effective than As+SMP for treating Schistosoma haematobium. However, the safety and tolerability profile of As+SMP was similar to that seen with PZQ. Our findings suggest that further investigations seem justifiable to determine the dose/efficacy/safety pattern of As+SMP in the treatment of Schistosoma infections.Trial Registration
ClinicalTrials.gov NCT00510159http://clinicaltrials.gov/ct2/show/NCT00510159 相似文献5.
Elizabeth P. Schlaudecker Mark C. Steinhoff Saad B. Omer Monica M. McNeal Eliza Roy Shams E. Arifeen Caitlin N. Dodd Rubhana Raqib Robert F. Breiman K. Zaman 《PloS one》2013,8(8)
Background
Antenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier ; http://clinicaltrials.gov/ct2/show/ NCT00142389). NCT00142389Methods and Findings
The Mother''s Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154).Conclusions
The sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the cellular and immunologic mechanisms of breast milk-mediated protection after antepartum immunization.Trial Registration
ClinicalTrials.gov NCT00142389相似文献6.
Joan Reibman Michael Marmor Joshua Filner Maria-Elena Fernandez-Beros Linda Rogers Guillermo I. Perez-Perez Martin J. Blaser 《PloS one》2008,3(12)
Background
Microbial exposures have been suggested to confer protection from allergic disorders and reduced exposures to gastrointestinal microbiota have been proposed as an explanation for the increase in asthma prevalence. Since the general prevalence of Helicobacter pylori has been decreasing, we hypothesized that H. pylori serostatus would be inversely related to the presence of asthma.Methods
Adults were recruited to participate in the New York University (NYU)/Bellevue Asthma Registry in New York City. Adult asthma cases (N = 318) and controls (N = 208) were identified and serum IgG antibodies to H. pylori whole cell antigens or the immunodominant CagA antigen were measured.Results
As expected, the asthma cases and controls differed with respect to atopy and lung function. Seropositivity to H. pylori or CagA antigen was present in 47.1% of the total case and control study population. Asthma was inversely associated with CagA seropositivity (OR = 0.57, 95% CI = 0.36–0.89). Median age of onset of asthma (doctor''s diagnosis) was older (21 years) among individuals with CagA+ strains than among H. pylori- individuals (11 years) (p = 0.006).Conclusion
These data are consistent with the hypothesis that colonization with CagA+ H. pylori strains is inversely associated with asthma and is associated with an older age of asthma onset in an urban population. The data suggest H. pylori as a marker for protection.Trial Registration
ClinicalTrials.gov NCT00212537相似文献7.
Azusa Hara Lutgarde Thijs Kei Asayama Lotte Jacobs Ji-Guang Wang Jan A. Staessen 《PloS one》2014,9(8)
Background
In the Systolic Hypertension in Europe trial (), we investigated whether systolic blood pressure variability determines prognosis over and beyond level. NCT02088450Methods
Using a computerised random function and a double-blind design, we randomly allocated 4695 patients (≥60 years) with isolated systolic hypertension (160–219/<95 mm Hg) to active treatment or matching placebo. Active treatment consisted of nitrendipine (10–40 mg/day) with possible addition of enalapril (5–20 mg/day) and/or hydrochlorothiazide (12.5–25.0 mg/day). We assessed whether on-treatment systolic blood pressure level (SBP), visit-to-visit variability independent of the mean (VIM) or within-visit variability (WVV) predicted total (n = 286) or cardiovascular (n = 150) mortality or cardiovascular (n = 347), cerebrovascular (n = 133) or cardiac (n = 217) endpoints.Findings
At 2 years, mean between-group differences were 10.5 mm Hg (p<0.0001) for SBP, 0.29 units (p = 0.20) for VIM, and 0.07 mm Hg (p = 0.47) for WVV. Active treatment reduced (p≤0.048) cardiovascular (−28%), cerebrovascular (−40%) and cardiac (−24%) endpoints. In analyses dichotomised by the median, patients with low vs. high VIM had similar event rates (p≥0.14). Low vs. high WVV was not associated with event rates (p≥0.095), except for total and cardiovascular mortality on active treatment, which were higher with low WVV (p≤0.0003). In multivariable-adjusted Cox models, SBP predicted all endpoints (p≤0.0043), whereas VIM did not predict any (p≥0.058). Except for an inverse association with total mortality (p = 0.042), WVV was not predictive (p≥0.15). Sensitivity analyses, from which we excluded blood pressure readings within 6 months after randomisation, 6 months prior to an event or both were confirmatory.Conclusions
The double-blind placebo-controlled Syst-Eur trial demonstrated that blood-pressure lowering treatment reduces cardiovascular complications by decreasing level but not variability of SBP. Higher blood pressure level, but not higher variability, predicted risk.Trial Registration
ClinicalTrials.gov NCT02088450相似文献8.
Jenneke Leentjens Jessica Quintin Jelle Gerretsen Matthijs Kox Peter Pickkers Mihai G. Netea 《PloS one》2014,9(9)
Rationale
To prevent or combat infection, increasing the effectiveness of the immune response is highly desirable, especially in case of compromised immune system function. However, immunostimulatory therapies are scarce, expensive, and often have unwanted side-effects. β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models. Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use.Methods
We performed a randomized open-label intervention pilot-study in 15 healthy male volunteers. Subjects were randomized to either the β -glucan (n = 10) or the control group (n = 5). Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days. Blood was sampled at various time-points to determine β-glucan serum levels, perform ex vivo stimulation of leukocytes, and analyze microbicidal activity.Results
β-glucan was barely detectable in serum of volunteers at all time-points. Furthermore, neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered β-glucan.Conclusion
The present study does not support the use of oral β-glucan to enhance innate immune responses in humans.Trial Registration
ClinicalTrials.gov NCT01727895相似文献9.
Kamal Ivory Andrew M. Wilson Prasanna Sankaran Marta Westwood Justin McCarville Claire Brockwell Allan Clark Jack R. Dainty Laurian Zuidmeer-Jongejan Claudio Nicoletti 《PloS one》2013,8(11)
Objective
To determine effects of probiotic consumption on clinical and immunological parameters of seasonal allergic rhinitis (SAR) in an out-of-season single nasal allergen challenge.Methods
In a study registered at ClinicalTrials.Gov (), a 16-week dietary intervention was undertaken in 60 patients with allergic rhinitis (>16 years old). Using a double-blinded, placebo-controlled anonymised design, the patients were divided equally into two groups. One group was given a dairy drink containing Lactobacillus casei Shirota to ingest daily while the other consumed a similar drink without bacteria. Participants attended the clinic on two consecutive days before the intervention and then again at the end of the study period. On the first day of each 2-day visit, following clinical examination, assessments were made of total nasal symptoms scores and peak nasal inspiratory flow. Nasal scrapings, nasal lavage and blood were collected for laboratory analyses of cellular phenotypes, soluble mediator release and in vitro responses to pollen allergen. These procedures were repeated 24 hours following nasal allergen challenge. NCT01123252Results
Prior to and following intervention there were no detectable differences between study groups in measured clinical outcome. After intervention, there were differences between groups in their percentages of CD86+ epithelial cells (p = 0.0148), CD86+CD252+ non-epithelial cells (p = 0.0347), sIL-1RII release (p = 0.0289) and IL-1β (p = 0.0224) levels at the nasal mucosa. Delivery of probiotic also suppressed production of sCD23 (p = 0.0081), TGF-β (p = 0.0283) and induced increased production of IFN-γ (p = 0.0351) in supernatants of cultured peripheral blood.Conclusions & Clinical Relevance
This study did not show significant probiotic-associated changes with respect to the primary clinical endpoint. An absence of overt clinical benefit may be due to an inability of single nasal challenges to accurately represent natural allergen exposure. Nevertheless, oral delivery of probiotics produced changes of the immunological microenvironment at the nasal mucosa in individuals affected by SAR.Trial Registration
ClinicalTrials.Gov NCT01123252相似文献10.
Neil M. Johannsen Lauren M. Sparks Zhengyu Zhang Conrad P. Earnest Steven R. Smith Timothy S. Church Eric Ravussin 《PloS one》2013,8(6)
Aims
To assess the determinants of exercise training-induced improvements in glucose control (HbA1C) including changes in serum total adiponectin and FFA concentrations, and skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein content.Methods
A sub-cohort (n = 35; 48% men; 74% Caucasian) from the HART-D study undertaking muscle biopsies before and after 9 months of aerobic (AT), resistance (RT), or combination training (ATRT).Results
Changes in HbA1C were associated with changes in adiponectin (r = −0.45, P = 0.007). Participants diagnosed with type 2 diabetes for a longer duration had the largest increase in PGC-1α (r = 0.44, P = 0.008). Statistical modeling examining changes in HbA1C suggested that male sex (P = 0.05), non-Caucasian ethnicity (P = 0.02), duration of type 2 diabetes (r = 0.40; P<0.002) and changes in FFA (r = 0.36; P<0.004), adiponectin (r = −0.26; P<0.03), and PGC-1α (r = −0.28; P = 0.02) explain ∼65% of the variability in the changes in HbA1C.Conclusions
Decreases in HbA1C after 9 months of exercise were associated with shorter duration of diabetes, lowering of serum FFA concentrations, increasing serum adiponectin concentrations and increasing skeletal muscle PGC-1α protein expression.Trial Registration
ClinicalTrials.gov NCT00458133相似文献11.
Eliane A. Lucassen Paolo Piaggi John Dsurney Lilian de Jonge Xiong-ce Zhao Megan S. Mattingly Angela Ramer Janet Gershengorn Gyorgy Csako Giovanni Cizza for the Sleep Extension Study Group 《PloS one》2014,9(1)
Background
Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.Objective
To characterize neurocognitive functions and assess its reversibility.Design
Prospective cohort study.Setting
Tertiary Referral Research Clinical Center.Patients
A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m2) men and pre-menopausal women.Intervention
Sleep extension (468±88 days) with life-style modifications.Measurements
Neurocognitive functions, sleep quality and sleep duration.Results
At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.Limitations
Drop-out rate.Conclusions
Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.Trail registration
www.ClinicalTrials.gov . NIDDK protocol 06-DK-0036 NCT00261898相似文献12.
Margaret Kweku Jayne Webster Martin Adjuik Samuel Abudey Brian Greenwood Daniel Chandramohan 《PloS one》2009,4(9)
Background
Intermittent preventive treatment for malaria in children (IPTc) is a promising new intervention for the prevention of malaria but its delivery is a challenge. We have evaluated the coverage of IPTc that can be achieved by two different delivery systems in Ghana.Methods
IPTc was delivered by volunteers in six villages (community-based arm) and by health workers at health centres or at Expanded Programme on Immunisation outreach clinics (facility based) in another six communities. The villages were selected randomly and drugs were administered in May, June, September and October 2006. The first dose of a three-dose regimen of amodiaquine plus sulphadoxine-pyrimethamine was administered under supervision to 3–59 month-old children (n = 964) in the 12 study villages; doses for days 2 and 3 were given to parents/guardians to administer at home.Results
The proportion of children who received at least the first dose of 3 or more courses of IPTc was slightly higher in the community based arm (90.5% vs 86.6%; p = 0.059). Completion of the three dose regimen was high and similar with both delivery systems (91.6% and 91.7% respectively).Conclusion
Seasonal IPTc delivered through community-based or facility-based systems can achieve a high coverage rate with the support and supervision of the district health management team. However, in order to maximise the impact of IPTc, both delivery systems may be needed in some settings.Trial Registration
ClinicalTrials.gov NCT00119132相似文献13.
Steven J. Reynolds Cissy Kityo Claire W. Hallahan Geoffrey Kabuye Diana Atwiine Frank Mbamanya Francis Ssali Robin Dewar Marybeth Daucher Richard T. Davey Jr Peter Mugyenyi Anthony S. Fauci Thomas C. Quinn Mark R. Dybul 《PloS one》2010,5(4)
Background
Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs.Methods
A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count ≥125 cells/mm3 and HIV RNA plasma levels <50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection.Results
Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39).Conclusions
Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy.Trial Registration
ClinicalTrials.gov NCT00339456相似文献14.
Esra' Shishtar John L. Sievenpiper Vladimir Djedovic Adrian I. Cozma Vanessa Ha Viranda H. Jayalath David J. A. Jenkins Sonia Blanco Meija Russell J. de Souza Elena Jovanovski Vladimir Vuksan 《PloS one》2014,9(9)
Importance
Despite the widespread use of ginseng in the management of diabetes, supporting evidence of its anti-hyperglycemic efficacy is limited, necessitating the need for evidence-based recommendations for the potential inclusion of ginseng in diabetes management.Objective
To elucidate the effect of ginseng on glycemic control in a systematic review and meta-analysis of randomized controlled trials in people with and without diabetes.Data sources
MEDLINE, EMBASE, CINAHL and the Cochrane Library (through July 3, 2013).Study selection
Randomized controlled trials ≥30 days assessing the glycemic effects of ginseng in people with and without diabetes.Data extraction
Relevant data were extracted by 2 independent reviewers. Discrepancies were resolved by consensus. The Heyland Methodological Quality Score and the Cochrane risk of bias tool were used to assess study quality and risk of bias respectively.Data synthesis
Sixteen trials were included, in which 16 fasting blood glucose (n = 770), 10 fasting plasma insulin (n = 349), 9 glycated hemoglobin (n = 264), and 7 homeostasis model assessment of insulin resistance (n = 305) comparisons were reported. Ginseng significantly reduced fasting blood glucose compared to control (MD = −0.31 mmol/L [95% CI: −0.59 to −0.03], P = 0.03). Although there was no significant effect on fasting plasma insulin, glycated hemoglobin, or homeostasis model assessment of insulin resistance, a priori subgroup analyses did show significant reductions in glycated hemoglobin in parallel compared to crossover trials (MD = 0.22% [95%CI: 0.06 to 0.37], P = 0.01).Limitations
Most trials were of short duration (67% trials<12wks), and included participants with a relatively good glycemic control (median HbA1c non-diabetes = 5.4% [2 trials]; median HbA1c diabetes = 7.1% [7 trials]).Conclusions
Ginseng modestly yet significantly improved fasting blood glucose in people with and without diabetes. In order to address the uncertainty in our effect estimates and provide better assessments of ginseng''s anti-diabetic efficacy, larger and longer randomized controlled trials using standardized ginseng preparations are warranted.Trial Registration
ClinicalTrials.gov NCT01841229相似文献15.
Mikael Engman Suby Varghese Kristina Lagerstedt Robinson Helena Malmgren Anna Hammarsj? Birgitta Bystr?m Parameswaran Grace L Lalitkumar Kristina Gemzell-Danielsson 《PloS one》2013,8(12)
Progesterone receptor modulators, such as mifepristone are useful and well tolerated in reducing leiomyoma volume although with large individual variation. The objective of this study was to investigate the molecular basis for the observed leiomyoma volume reduction, in response to mifepristone treatment and explore a possible molecular marker for the selective usage of mifepristone in leiomyoma patients. Premenopausal women (N = 14) were treated with mifepristone 50 mg, every other day for 12 weeks prior to surgery. Women were arbitrarily sub-grouped as good (N = 4), poor (N = 4) responders to treatment or intermediate respondents (N = 3). Total RNA was extracted from leiomyoma tissue, after surgical removal of the tumour and the differential expression of genes were analysed by microarray. The results were analysed using Ingenuity Pathway Analysis software. The glutathione pathway was the most significantly altered canonical pathway in which the glutathione-s transferase mu 1 (GSTM1) gene was significantly over expressed (+8.03 folds) among the good responders compared to non responders. This was further confirmed by Real time PCR (p = 0.024). Correlation of immunoreactive scores (IRS) for GSTM1 accumulation in leiomyoma tissue was seen with base line volume change of leiomyoma R = −0.8 (p = 0.011). Furthermore the accumulation of protein GSTM1 analysed by Western Blot correlated significantly with the percentual leiomyoma volume change R = −0.82 (p = 0.004). Deletion of the GSTM1 gene in leiomyoma biopsies was found in 50% of the mifepristone treated cases, with lower presence of the GSTM1 protein. The findings support a significant role for GSTM1 in leiomyoma volume reduction induced by mifepristone and explain the observed individual variation in this response. Furthermore the finding could be useful to further explore GSTM1 as a biomarker for tailoring medical treatment of uterine leiomyomas for optimizing the response to treatment.
Clinical Trials identifier
www.clinicaltrials.gov: , Protocol date: November 2004. http://clinicaltrials.gov/ct2/show/ NCT00579475 NCT00579475相似文献16.
Dorit Samocha-Bonet Donald J. Chisholm Fiona M. Gribble Adelle C. F. Coster Kevin H. Carpenter Graham R. D. Jones Jens J. Holst Jerry R. Greenfield 《PloS one》2014,9(11)
Background and Aims
L-glutamine is an efficacious glucagon-like peptide (GLP)-1 secretagogue in vitro. When administered with a meal, glutamine increases GLP-1 and insulin excursions and reduces postprandial glycaemia in type 2 diabetes patients. The aim of the study was to assess the efficacy and safety of daily glutamine supplementation with or without the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin in well-controlled type 2 diabetes patients.Methods
Type 2 diabetes patients treated with metformin (n = 13, 9 men) with baseline glycated hemoglobin (HbA1c) 7.1±0.3% (54±4 mmol/mol) received glutamine (15 g bd)+ sitagliptin (100 mg/d) or glutamine (15 g bd) + placebo for 4 weeks in a randomized crossover study.Results
HbA1c (P = 0.007) and fructosamine (P = 0.02) decreased modestly, without significant time-treatment interactions (both P = 0.4). Blood urea increased (P<0.001) without a significant time-treatment interaction (P = 0.8), but creatinine and estimated glomerular filtration rate (eGFR) were unchanged (P≥0.5). Red blood cells, hemoglobin, hematocrit, and albumin modestly decreased (P≤0.02), without significant time-treatment interactions (P≥0.4). Body weight and plasma electrolytes remained unchanged (P≥0.2).Conclusions
Daily oral supplementation of glutamine with or without sitagliptin for 4 weeks decreased glycaemia in well-controlled type 2 diabetes patients, but was also associated with mild plasma volume expansion.Trial Registration
ClincalTrials.gov NCT00673894相似文献17.
Samir K. Gupta Deming Mi Michael P. Dubé Chandan K. Saha Raymond M. Johnson James H. Stein Matthias A. Clauss Kieren J. Mather Zeruesenay Desta Ziyue Liu 《PloS one》2013,8(4)
Background
Untreated HIV may increase the risk of cardiovascular events. Our preliminary in vitro and in vivo research suggests that pentoxifylline (PTX) reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy.Methods
We performed a randomized, placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants. The primary endpoint was change in flow-mediated dilation (FMD) of the brachial artery after 8 weeks. Nitroglycerin-mediated dilation (NTGMD) and circulating markers of inflammation, cellular immune activation, coagulation, and metabolism were also assessed.Results
The difference in mean absolute change (SD) in FMD after 8 weeks between the placebo [−1.06 (1.45)%] and PTX [−1.93 (3.03)%] groups was not significant (P = 0.44). No differences in NTGMD were observed. The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 (sTNFRI) [−83.2 pg/mL in the placebo group vs. +65.9 pg/mL in the PTX group; P = 0.03]. PTX was generally well-tolerated.Conclusions
PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy. Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population.Trial Registration
ClinicalTrials.gov NCT00796822相似文献18.
Saloua El Messaoudi Tim H. Schreuder Roel D. Kengen Gerard A. Rongen Petra H. van den Broek Dick H. J. Thijssen Niels P. Riksen 《PloS one》2014,9(4)
Introduction
Large prospective studies in patients with type 2 diabetes mellitus have demonstrated that metformin treatment improves cardiovascular prognosis, independent of glycemic control. Administration of metformin potently limits infarct size in murine models of myocardial infarction. This study examined, for the first time in humans, whether metformin limits ischemia-reperfusion (IR) injury in vivo using a well-validated forearm model of endothelial IR-injury.Methods
Twenty-eight healthy volunteers (age 41±6 years, 10 male/16 female) were randomized between pretreatment with metformin (500 mg three times a day for 3 days) or no treatment in a Prospective Randomized Open Blinded Endpoint study. Brachial artery flow mediated dilation (FMD) was measured before and after 20 minutes of forearm ischemia and 20 minutes of reperfusion. FMD analysis was performed offline by investigators blinded for the treatment arm.Results
Baseline FMD did not differ between metformin pretreatment and no pretreatment (6.9±3.6% and 6.1±3.5%, respectively, p = 0.27, n = 26). FMD was significantly lower after forearm IR in both treatment arms (4.4±3.3% and 4.3±2.8%, respectively, P<0.001 in both conditions). A linear mixed model analysis revealed that metformin treatment did not prevent the decrease in FMD by IR.Conclusion
A 3 day treatment with metformin in healthy, middle-aged subjects does not protect against endothelial IR-injury, measured with brachial artery FMD after forearm ischemia. Further studies are needed to clarify what mechanism underlies the cardiovascular benefit of metformin treatment.Trial Registration
ClinicalTrials.gov NCT01610401相似文献19.
Vera Halpern Folasade Ogunsola Orikomaba Obunge Chin-Hua Wang Nneka Onyejepu Oyinola Oduyebo Doug Taylor Linda McNeil Neha Mehta John Umo-Otong Sakiru Otusanya Tania Crucitti Said Abdellati 《PloS one》2008,3(11)
Background
This trial evaluated the safety and effectiveness of 6% cellulose sulfate vaginal gel in preventing male-to-female vaginal transmission of HIV, gonorrhea and chlamydial infection.Methods
This Phase III, double-blind, randomized, placebo-controlled trial was conducted between November 2004 and March 2007 in Lagos and Port Harcourt, Nigeria. We enrolled 1644 HIV-antibody negative women at high risk of HIV acquisition. Study participants were randomized 1∶1 to cellulose sulfate or placebo and asked to use gel plus a condom for each act of vaginal intercourse over one year of follow-up. The participants were evaluated monthly for HIV, gonorrhea and chlamydial infection, and for adverse events.Results
The trial was stopped prematurely after the data safety monitoring board of a parallel trial concluded that cellulose sulfate might be increasing the risk of HIV. In contrast, we observed fewer infections in the active arm (10) than on placebo (13), a difference that was nonetheless not statistically significant (HR = 0.8, 95% CI 0.3–1.8; p = 0.56). Rates of gonorrhea and chlamydial infection were lower in the CS group but the difference was likewise not statistically significant (HR = 0.8, 95% CI 0.5–1.1; p = 0.19 for the combined STI outcome). Rates of adverse events were similar across study arms. No serious adverse events related to cellulose sulfate use were reported.Conclusions
Cellulose sulfate gel appeared to be safe in the evaluated study population but we found insufficient evidence that it prevented male-to-female vaginal transmission of HIV, gonorrhea or chlamydial infection. The early closure of the trial compromised the ability to draw definitive conclusions about the effectiveness of cellulose sulfate against HIV.Trial Registration
ClinicalTrials.gov NCT00120770相似文献20.
Marcia R. Weaver Ian Crozier Simon Eleku Gyaviira Makanga Lydia Mpanga Sebuyira Janepher Nyakake MaryLou Thompson Kelly Willis 《PloS one》2012,7(12)