Effects of Long-Term Fixed Orthodontic Treatment on Salivary Nickel and Chromium Levels: a 1-Year Prospective Cohort Study

Effect of long-term orthodontic treatment on salivary nickel and chromium has not been quite assessed except in few retrospective studies with controversial results. The aim of this prospective study was to measure salivary levels of these ions during 1?year of orthodontic treatment. Saliva samples were collected from 20 orthodontic patients, before treatment (control) and 6 and 12?months later. Nickel and chromium concentrations were determined using atomic absorption spectrophotometry. Data were analyzed using one- and two-way repeated-measures ANOVA, Bonferroni, Friedman (???=?0.05), and Wilcoxon signed-ranks tests (???=?0.016). Average nickel level changed from 9.75?±?5.02 to 10.37?±?6.94 and then to 8.32?±?4.36???g/L in 1?year. Average chromium concentration changed from 3.86?±?1.34 to 4.6?±?6.11 and then to 2.04?±?1.66???g/L. Alterations in nickel values were not statistically significant [P?=?0.468 (ANOVA)], but fluctuations in chromium levels were [P?=?0.021 (Friedman)]. The decrease in chromium concentration after 12?months was significant compared to the control [P?=?0.004 (Wilcoxon)]. Although slightly increased after 6?months, the concentration of both ions dropped to levels slightly lower than the control groups after 12?months.     

Effect of Fixed Orthodontic Therapy on Urinary Nickel Levels: A Long-term Retrospective Cohort Study

Nickel constitutes about 8?C60?% of orthodontic alloys. It is known as an allergenic/cytotoxic trace metal. Therefore, it should be investigated in patients undergoing orthodontic treatment which might last for 2 or 3?years. However, no controlled studies have assessed the influence of orthodontic treatments of longer than 5?months on its systemic levels. Thus, the aim of this retrospective cohort study was to evaluate systemic nickel in patients undergoing orthodontic therapy for a minimum period of 1?year. In this study, urinary nickel concentrations in 20 female and 10 male patients being treated with stainless steel appliances were measured using atomic absorption spectrophotometry. The same procedure was done on a control group of the patients?? same-gender near-age siblings (n?=?30). The effect of treatment and gender on urinary nickel levels were assessed using a repeated-measures two-way analysis of variance (ANOVA) and a Tukey test (???=?0.05). The mean treatment duration was 17.1?±?6.4?months (range, 12?C21). The mean nickel concentrations in male and female patients were 9.67?±?3.25 and 9.9?±?3.83???g/L, respectively. These statistics for male and female control subjects were 6.65?±?2.57 and 8.43?±?2.94???g/L, respectively. The ANOVA showed a statistically significant difference between the urinary nickel levels of the treatment and the control groups (P?=?0.009) but not between the genders (P?=?0.194). The interaction between gender and treatment was also nonsignificant (P?=?0.337). The Tukey test indicated that the increase in nickel was higher in male patients, in comparison to their brothers (P?<?0.05). It could be concluded that orthodontic therapy for longer durations with stainless-steel archwires might elevate slightly, but significantly, urinary nickel levels.     

Varenicline Effects on Smoking,Cognition, and Psychiatric Symptoms in Schizophrenia: A Double-Blind Randomized Trial

Schizophrenic patients have a high rate of smoking and cognitive deficits which may be related to a decreased number or responsiveness of nicotinic receptors in their brains. Varenicline is a partial nicotinic agonist which is effective as an antismoking drug in cigarette smokers, although concerns have been raised about potential psychiatric side-effects. We conducted a double-blind placebo controlled study in 87 schizophrenic smokers to evaluate the effects of varenicline (2 mg/day) on measures of smoking, cognition, psychiatric symptoms, and side-effects in schizophrenic patients who were cigarette smokers. Varenicline significantly decreased cotinine levels (P<0.001), and other objective and subjective measures of smoking (P < .01), and responses on a smoking urges scale (P = .02), more than placebo. Varenicline did not improve scores on a cognitive battery designed to test the effect of drugs on cognitive performance in schizophrenia (the MATRICS battery), either in overall MATRICS battery Composite or individual Domain scores, more than placebo. There were no significant differences between varenicline vs. placebo effects on total symptom scores on psychiatric rating scales, PANSS, SANS, or Calgary Depression scales, and there were no significant drug effects in any of these scales sub-scores when we used Benjamin-Hochberg corrected significance levels (α = .05). Varenicline patients did not show greater side-effects than placebo treated patients at any time point when controlled for baseline side-effect scores. Our study supports the use of varenicline as a safe drug for smoking reduction in schizophrenia but not as a cognitive enhancer.Trial Registration: ClinicalTrials.gov 00802919     

Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized,Double-Blind Placebo-Controlled Clinical Trial

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 {"type":"clinical-trial","attrs":{"text":"NCT01299948","term_id":"NCT01299948"}}NCT01299948). 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.

Results

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 {"type":"clinical-trial","attrs":{"text":"NCT01299948","term_id":"NCT01299948"}}NCT01299948     

The Role of Probiotics in the Treatment of Dysentery: a Randomized Double-Blind Clinical Trial

Diarrhea is considered as an important cause of morbidity and mortality, even though one of the main reasons of death following diarrhea is initiated by dysentery. In recent years, the consumption of probiotics has been proposed for the treatment of infectious diarrhea. Despite most of the studies on probiotics have focused on acute watery diarrhea, few studies in the field of dysentery have found beneficial effects of probiotics. This study is a randomized double-blind clinical trial. The patients were randomly placed into control and case groups. In the intervention group, the patients received probiotics in the form of Kidilact® sachet, which contained high amounts of 7-strain friendly bacteria strains of Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium infantis, Bifidobacterium breve, and Streptococcus thermophiles. On the other hand, the patients in the control group received placebo sachets on a daily basis for 5 days. It is notable that the treatment protocol of acute dysentery was done on both groups. The results of this study showed significant differences in the duration of blood in diarrhea between probiotic consumers (2.62 days) and the control group (3.16 days) (P value = 0.05). Additionally, significant differences in the average length of hospitalization in probiotic consumers (3.16 days) and control (3.66 days), (P value = 0.02) could be claimed that the consumption of probiotics is effective in reducing the duration of dysentery and diarrhea. The results of this study suggest that the use of probiotics can be effective in reducing the duration of blood in diarrhea. This study was also recorded in the Iran center of clinical trials registration database (IRCT2014060617985N1).     

The Effect of Fixed Orthodontic Appliances and Fluoride Mouthwash on the Oral Microbiome of Adolescents – A Randomized Controlled Clinical Trial

While the aesthetic effect of orthodontic treatment is clear, the knowledge on how it influences the oral microbiota and the consequential effects on oral health are limited. In this randomized controlled clinical trial we investigated the changes introduced in the oral ecosystem, during and after orthodontic treatment with fixed appliances in combination with or without a fluoride mouthwash, of 10–16.8 year old individuals (N = 91). We followed several clinical parameters in time, in combination with microbiome changes using next-generation sequencing of the bacterial 16S rRNA gene. During the course of our study, the oral microbial community displayed remarkable resilience towards the disturbances it was presented with. The effects of the fluoride mouthwash on the microbial composition were trivial. More pronounced microbial changes were related to gingival health status, orthodontic treatment and time. Periodontal pathogens (e.g. Selenomonas and Porphyromonas) were highest in abundance during the orthodontic treatment, while the health associated Streptococcus, Rothia and Haemophilus gained abundance towards the end and after the orthodontic treatment. Only minor compositional changes remained in the oral microbiome after the end of treatment. We conclude that, provided proper oral hygiene is maintained, changes in the oral microbiome composition resulting from orthodontic treatment are minimal and do not negatively affect oral health.     

Effects of Sodium Bicarbonate on High-Intensity Endurance Performance in Cyclists: A Double-Blind,Randomized Cross-Over Trial

Background

While the ergogenic effect of sodium bicarbonate (BICA) on short-term, sprint-type performance has been repeatedly demonstrated, little is known about its effectiveness during prolonged high-intensity exercise in well-trained athletes. Therefore, this study aims to examine the influence of BICA on performance during exhaustive, high-intensity endurance cycling.

Methods

This was a single-center, double-blind, randomized, placebo-controlled cross-over study. Twenty-one well-trained cyclists (mean ± SD: age 24±8 y, BMI 21.3±1.7, VO_2peak 67.3±9.8 ml·kg⁻¹·min⁻¹) were randomly allocated to sequences of following interventions: oral ingestion of 0.3 g·kg⁻¹ BICA or 4 g of sodium chloride (placebo), respectively. One h after ingestion subjects exercised for 30 min at 95% of the individual anaerobic threshold (IAT) followed by 110% IAT until exhaustion. Prior to these constant load tests stepwise incremental exercise tests were conducted under both conditions to determine IAT and VO_2peak. Analysis of blood gas parameters, blood lactate (BLa) and gas exchange measurements were conducted before, during and after the tests. The main outcome measure was the time to exhaustion in the constant load test.

Results

Cycling time to exhaustion was improved (p<0.05) under BICA (49.5±11.5 min) compared with placebo (45.0±9.5 min). No differences in maximal or sub-maximal measures of performance were observed during stepwise incremental tests. BICA ingestion resulted in an increased pH, bicarbonate concentration and BLa before, throughout and after both exercise testing modes.

Conclusion

The results suggest that ingestion of BICA may improve prolonged, high-intensity cycling performance.

Trial Registration

German Clinical Trials Register (DRKS) DRKS00006198.     

T Cell Vaccination Benefits Relapsing Progressive Multiple Sclerosis Patients: A Randomized,Double-Blind Clinical Trial

Background

T-cell vaccination (TCV) for multiple sclerosis (MS) refers to treatment with autologous anti-myelin T-cells, attenuated by irradiation. Previously published clinical trials have been all open-labeled.

Aim

To evaluate the safety and efficacy of TCV in progressive MS, in a double-blind, controlled clinical trial.

Methodology

Twenty-six patients with relapsing-progressive MS were enrolled in the study (mean age: 39±9.8 years; mean EDSS: 4.4±1.7). T-cell lines reactive to 9 different peptides of the myelin antigens, MBP, MOG and PLP were raised from the patients'' peripheral blood. The patients were randomized into two groups: 19 were treated with TCV (four subcutaneous injections of 10–30×10⁶ T-cells, attenuated by irradiation, on days 1, 30, 90 and 180) and 7 patients were treated with sham injections. Twenty-four patients (17 in the TCV group and 7 in the placebo) were eligible for per-protocol analysis.

Results

At one year following the inclusion, an increase in the EDSS (+0.50) and an increase in 10-meter walking time (+0.18 sec), were observed in the placebo group; in the TCV group there was a decrease in the EDSS (−0.44; p<0.01) and in the 10-meter walking time (0.84 sec; p<0.005). Sixteen of the 17 patients (94.1%) in the TCV group remained relapse-free during the year of the study, as compared to 42.9% in the placebo group (p = 0.01 and p = 0.03 with adjustment). The proportion of patients with any relapse during the year of the study in the TCV-group, was reduced by 89.6%., as compared to the placebo-treated group. MRI parameters did not change significantly.

Conclusions

This is the first controlled, double-blind trial with TCV in progressive MS. The results demonstrate the feasibility and safety of the procedure, and provide significant indications of clinical efficacy. Further studies with larger groups of subjects are warranted.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01448252","term_id":"NCT01448252"}}NCT01448252     

Potassium Citrate Decreases Bone Resorption in Postmenopausal Women with Osteopenia: A Randomized,Double-Blind Clinical Trial

Objective: Diets rich in animal protein, such as the typical American diet, are thought to create a high acid load. An association between acid load and bone loss has led to the idea that providing positive alkaline salt therapy could have beneficial effects on bone metabolism. The objective of this study was to investigate the effects of potassium citrate (K-citrate), 40 mEq daily, over 1 year on bone resorption and formation.Methods: A randomized, double-blind, placebo-controlled trial of 83 women with postmenopausal osteopenia. Levels of bone turnover markers, specifically urinary N-telopeptide of collagen type 1 (u-NTX), amino-terminal propeptide of type 1 procollagen (P1NP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) were compared. Changes in bone mineral density (BMD) were also examined.Results: K-citrate decreased both u-NTX (P = .005) and serum P1NP (P<.001) starting at month 1 and continuing through month 12. No significant change was seen in BSAP or OC. No significant change was seen in lumbar or hip BMD between the 2 groups.Conclusion: In women with postmenopausal osteopenia, treatment with K-citrate for 1 year resulted in a significant decrease in markers of turnover. The effect on markers of bone formation was not consistent. K-citrate may serve as a potential treatment for bone loss that is well tolerated and without any significant known long-term consequences.Abbreviations:BMD = bone mineral densityBSAP = bone-specific alkaline phosphataseCa:Cr = calcium to creatinine ratioCTSC = Clinical Translational Science CenterCV = coefficient of variationDXA = dual-energy X-ray absorptiometryK-citrate = potassium citrateOC = osteocalcinP1NP = amino-terminal propeptide of type 1 procollagenu-NTX = urinary N-telopeptide of collagen type 1     

Salivary Nickel and Chromium Levels in Orthodontic Patients with and Without Periodontitis: a Preliminary Historical Cohort Study

Many periodontal patients may need orthodontic treatment. Alterations in oral environment particularly the reduction of pH in periodontal patients could affect metal ion release from orthodontic appliances. However, there is no study on metal ion release in periodontal patients. The aim of this preliminary study was to comparatively evaluate, for the first time, salivary levels of nickel and chromium in periodontal patients (versus healthy controls) under orthodontic treatment for 2 months. In this in vivo study, 40 subjects were evaluated. Patient selection and standardization of orthodontic treatment protocols were prospectively designed and performed. Two groups of n = 20 each (control: healthy orthodontic patients, cohort: orthodontic patients with periodontitis) underwent similar protocols of fixed orthodontic treatment for 2 months. After 2 months, salivary nickel and chromium concentrations of the case and cohort groups were measured using inductively coupled plasma mass spectrometry (ICP-MS). The values were compared between the two groups using t test. There were 10 men and 10 women in each group. The mean age of patients was 34.6 ± 3.6 years old. The salivary level of nickel was 338.2 ± 235.5 ng/ml and 182.8 ± 116.5 ng/ml in the cohort and control groups, respectively (P = 0.0118). The salivary level of chromium was 7.4 ± 3.15 ng/ml in the cohort and 6.35 ± 2.39 ng/ml in the control group (P = 0.2214). Salivary level of nickel might be considerably higher in periodontal patients undergoing 2 months of orthodontic treatment compared to orthodontic patients with healthy gingivae.

     

DNA Priming for Seasonal Influenza Vaccine: A Phase 1b Double-Blind Randomized Clinical Trial

BackgroundThe efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost.MethodsFour sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective.ResultsThe DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study.ConclusionWhile DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01498718","term_id":"NCT01498718"}}NCT01498718     

Effects of Zinc Supplement on Plasma Homocysteine Level in End-Stage Renal Disease Patients: a Double-Blind Randomized Clinical Trial

Increased homocysteine (hCys) level is an independent risk factor for cardiovascular complications in end-stage renal disease (ESRD) patients. The aim of this study was to evaluate effect of zinc (Zn) supplement on serum hCys level in ESRD patients. One hundred ESRD patients with Zn deficiency were enrolled in this double-blind randomized clinical trial. They were randomly subdivided into two groups and supplemented with Zn (Zn group) or placebo (control group) for 6 weeks. Fasting plasma hCys and Zn levels were measured before and at 43rd days after the start of the study. Serum Zn levels increased significantly (p?<?0.0001), in Zn-treated group in comparison to placebo-treated group. In the Zn-treated group, serum hCys levels reduced significantly (p?<?0.0001), compared to placebo group (p?>?0.05). There was a significant (p?<?0.0001) reduction of mean percentage of hCys in Zn-treated group compared to the placebo group. Our study showed that Zn supplementation decreases serum hCys levels in ESRD patients with Zn deficiency.     

Intravenous Amantadine for Freezing of Gait Resistant to Dopaminergic Therapy: A Randomized,Double-Blind,Placebo-Controlled,Cross-Over Clinical Trial

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 therapy

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01313819","term_id":"NCT01313819"}}NCT01313819     

The Effects of Synbiotic Supplementation on Metabolic Status in Women With Polycystic Ovary Syndrome: a Randomized Double-Blind Clinical Trial

Probiotics and Antimicrobial Proteins - Data on the effects of synbiotic supplementation on glycemic control, lipid profiles, and atherogenic index of plasma (AIP) of women with polycystic ovary...     

A Multicenter,Randomized, Double-Blind,Placebo-Controlled Trial of High-Dose Rebamipide Treatment for Low-Dose Aspirin-Induced Moderate-to-Severe Small Intestinal Damage

Background

Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant.

Aim

We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy.

Methods

We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks.

Results

The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated.

Conclusions

High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy.

Trial Registration

UMIN Clinical Trials Registry UMIN000003463     

Sporozoite Immunization of Human Volunteers under Mefloquine Prophylaxis Is Safe,Immunogenic and Protective: A Double-Blind Randomized Controlled Clinical Trial

Immunization of healthy volunteers with chloroquine ChemoProphylaxis and Sporozoites (CPS-CQ) efficiently and reproducibly induces dose-dependent and long-lasting protection against homologous Plasmodium falciparum challenge. Here, we studied whether chloroquine can be replaced by mefloquine, which is the only other licensed anti-malarial chemoprophylactic drug that does not affect pre-erythrocytic stages, exposure to which is considered essential for induction of protection by CPS immunization. In a double blind randomized controlled clinical trial, volunteers under either chloroquine prophylaxis (CPS-CQ, n = 5) or mefloquine prophylaxis (CPS-MQ, n = 10) received three sub-optimal CPS immunizations by bites from eight P. falciparum infected mosquitoes each, at monthly intervals. Four control volunteers received mefloquine prophylaxis and bites from uninfected mosquitoes. CPS-MQ immunization is safe and equally potent compared to CPS-CQ inducing protection in 7/10 (70%) versus 3/5 (60%) volunteers, respectively. Furthermore, specific antibody levels and cellular immune memory responses were comparable between both groups. We therefore conclude that mefloquine and chloroquine are equally effective in CPS-induced immune responses and protection.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01422954","term_id":"NCT01422954"}}NCT01422954     

Effect of Sitagliptin on Post-Prandial Glucagon and GLP-1 Levels in Patients With Type 1 Diabetes: Investigator-Initiated,Double-Blind,Randomized, Placebo-Controlled Trial

ObjectivePeripheral insulin resistance in type 1 diabetes may be related to a paradoxical postprandial glucagon increase. This study evaluated the effects of sitagliptin (dipeptidyl peptidase-IV [DPP-IV] inhibitor, approved for patients with type 2 diabetes), in adults with type 1 diabetes to improve glycemic control through decreasing postprandial glucagon.MethodsThis investigator-initiated, double-blind, randomized-parallel 20-week study enrolled 141 subjects. Subjects received sitagliptin 100 mg/day or placebo for 16 weeks. A subset of 85 patients wore blinded continuous glucose monitors (CGM) for 5 separate 7-day periods. The primary outcome was post-meal (Boost™) reduction in 4-hour glucagon area under the curve (AUC). Secondary endpoints included changes in glycated hemoglobin (A1c), CGM data, insulin dose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and C-peptide levels.ResultsThere were no differences at screening between groups; however, after a 4-week run-in phase, A1c was significantly lower in the sitagliptin vs. placebo group. Post-meal GLP-1 levels were higher (P<.001) and GIP levels lower (P = .03), with glucagon suppression at 30 minutes (LS means 23.2 ± 1.9 versus 16.0 ± 1.8; P = .006) in the sitagliptin group at 16 weeks. There were no differences between the groups in change in A1c, insulin dose, weight, or C-peptide after 16 weeks of treatment. However, C-peptide positive patients randomized to sitagliplin had a non-significant trend toward decrease in A1c, mean glucose, and time spent in hyperglycemia.ConclusionSitagliptin use in type 1 diabetes did not change glucagon AUC, A1c, insulin dose, or weight despite post-meal rise in GLP-1 levels. C-peptide positive subjects treated with sitagliptin had a nonsignificant trend in decreasing hyperglycemia, which needs further evaluation. (Endocr Pract. 2013;19:19-28)     

Caffeine Intake,Short Bouts of Physical Activity,and Energy Expenditure: A Double-Blind Randomized Crossover Trial

PA energy expenditure (PAEE) is the most variable component of Total Energy Expenditure (TEE) and largely due to the balance of sedentary time (SedT) and low intensity physical activity (LIPA). There has been an emergence for seeking an understanding of factors which determine variations in SedT, LIPA, and PAEE. Sedentary behavior and physical activity are relatively resistant to change by experimental dietary treatments and significant body weight changes. Although caffeine (Caf) is by far the most heavily used nutritional agent ingested to promote a sense of vigor/alertness, it is still unknown if Caf is effective in increasing PAEE and physical activity. The aim of the study was to test the hypothesis that 2 daily doses of Caf (as a capsule to blind the treatment and divided equally during breakfast and lunch) increase PAEE and TEE, and it would do so through increasing the frequent and brief bouts of physical activity (~1-5 min long) through the day as measured by accelerometry. In 21 low Caf users (<100 mg day^-1), we used a double-blind crossover trial (ClinicalTrials.govID;{"type":"clinical-trial","attrs":{"text":"NCT01477294","term_id":"NCT01477294"}}NCT01477294) with two conditions (4-day each with a 3-day washout period) randomly ordered as 5 mg kg^-1 day^-1 of Caf and maltodextrin as placebo (Plc). Resting energy expenditure (REE) by indirect calorimetry, total energy expenditure (TEE) from doubly labeled water, PAEE calculated as TEE-(REE+0.1TEE), and accelerometry measurements of both LIPA and MVPA were not different between conditions. However, regardless of caffeine or placebo, there were several significant relationships between brief bouts of LIPA and MVPA with PAEE. In conclusion, this double-blind study found that low and moderate-vigorous activity as well as the total volume of PAEE in free-living conditions is resistant to dietary caffeine intake that was equivalent to 5 cups of espresso or 7 cups of tea.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01477294","term_id":"NCT01477294"}}NCT01477294     

Effects of Two Chinese Herbal Formulae for the Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease: A Multicenter,Double-Blind,Randomized Controlled Trial

Objective

The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD.

Methods

A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol.

Results

A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV₁ (%) and FEV₁/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P<0.05), IL-1β (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-α. Both treatments slightly descended TGF-β1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups.

Conclusions

BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general.

Trial Registration

Chinese Clinical Trial Register center ChiCTR-TRC-09000530