Double-blind Crossover Clinical Trial Research Articles

Differences in the Effect of Plant Sterols on Lipid Metabolism in Men and Women

Plant sterols are recommended to decrease low-density lipoprotein cholesterol (LDL-C). Possible differences between sexes in efficacy were analyzed. In a double-blind crossover clinical trial, 30 women and 24 men were divided into 2 phases of 3 weeks, separated by a 2-week washout period. Subjects ingested 2.23 g/day of sterols in 700-mL milk. Total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglyceride, and non-HDL-C were assessed. There was significant interaction of sex factors×time intervention in TC (F(1.49) = 4.54, η2 = 0.085), LDL-C (F(1.46) = 4.72, η2 = 0.093), HDL-C (F(1.48) = 9.37, η2 = 0.163), and non-HDL-C (F(1.48) = 9.97, η2 = 0.172). Total body fat in the control group and cholesterol reduction were significantly correlated with LDL-C (r = 0.463) and non-HDL-C (r = 0.482) reduction percentage (P < .05). Differences in sex effect were observed.

Combination of obstructive sleep apnoea and insomnia treated by continuous positive airway pressure with the SensAwake pressure relief technology to assist sleep: a randomised cross-over trial protocol

IntroductionObstructive sleep apnoea (OSA) is a common sleep breathing disorder affecting up to 17% of the middle-aged population. Continuous positive airway pressure (CPAP) is the primary treatment for patients with...

The Safety, Pharmacokinetics, and Nervous System Effects of Two Natural Sources of Caffeine in Healthy Adult Males.

This double‐blind crossover clinical trial randomized 12 adult males to receive 200 mg of caffeine from a green coffee extract, a guayusa leaf extract, and a synthetic control to compare their safety, absorption, and effect on neurotransmitters. The results showed no statistically significant changes in blood pressure or heart rate from baseline to 120 min postdose of each natural source compared with changes from baseline in the control (0.094 < = P < = 0.910). The ratios of Cmax, AUC0‐4, and AUC0‐∞ of each natural source to the control were bioequivalent by US Food and Drug Administration standards (90% CI within 80–125%). The guayusa leaf extract stimulated a significantly lower increase in epinephrine compared with the control (+0.5 vs. +2.78 μg/gCr, P = 0.04), while the green coffee extract provoked an increase in epinephrine similar to the control (+3.21 vs. +2.78 μg/gCr, P = 0.569). Implications for future clinical research are discussed.

Paracetamol 325mg/tramadol 37.5mg effect on pain during needle electromyography: a double-blind crossover clinical trial.

Needle insertion during electromyography (EMG) may cause varying levels of pain that could lead to inaccurate assessment and premature termination of the procedure. The aim of this study is to compare paracetamol 325mg/tramadol 37.5mg with placebo in relieving pain before EMG. This is a randomized, crossover, placebo-controlled, double-blind clinical trial; forty-four healthy individuals, including 27 males with a mean age of 35.3years (range 18-59years), entered this study. The needles were inserted unilaterally 2h after administration of two analgesic tablets of paracetamol 325mg/tramadol 37.5mg or two placebo tablets. The pain was scored through a 100-mm visual analog scale (VAS) immediately and 2h after the procedure. The side effects were also recorded. Within a week, the procedure was repeated on the other upper limb, changing the treatment and placebo. The immediate and 2-h VAS scores were notably lower after administration of treatment compared to placebo (immediate pain: 17.5±12.8 vs. 32.1±16.0, P<0.001; and 2-h pain: 1.6±5.6 vs. 5.8±7.9, P=0. 002). There was a higher prevalence of side effects when treatment was used (48 vs. 9%, P<0.001). Although most symptoms were mild, transient and resolved without medical interventions, on one occasion a volunteer experienced brief loss of consciousness and one subject had severe vertigo that required hospitalization and fluid therapy. Paracetamol 325mg/tramadol 37.5mg administration prior to EMG could effectively alleviate pain. Further application of this medication in patients with neuromuscular disorders would warrant additional clinical trials, particularly considering the adverse events.

Ficus carica Leaves Decoction on Glycemic Factors of Patients With Type 2 Diabetes Mellitus: A Double-Blind Clinical Trial

Background: It is advisable to pay sufficient heed to the high prevalence of diabetes mellitus (DM) management, which has heavy burden and remarkable impact on the patients` life quality. Objectives: The current study aimed to evaluate hypoglycemic effects of Ficus carica (FC) decoction (common fig leaf) in patients with type 2 DM. Patients and Methods: It was a double-blind cross-over clinical trial. There were two groups of 14 subjects. During the first phase of the study, one group received fig leaf decoction for 21 days and the other one received green tea as placebo. After a one-week wash-out period, the patients changed their medications and continued for another 21 days. Variables including fasting blood sugar (FBS), 2 hours postprandial blood sugar (2hpp), fructosamine, HbA1c, C-peptide, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed at baseline, and at the end of two phases of the study and were compared. Results: Thirteen patients in each group completed the trial. FBS, fructosamine, HbA1c, and C-peptide baseline and post-trial amounts in the case group were 152.76 ± 53.75, 146.92 ± 51.28 mg/dL (P = 0.073), 2.92 ± 0.515, 2.83 ± 0.482 mM/L (P = 0.276), 7.48% ± 0.535, 7.33% ± 0.532 (P = 0.114), 2.90 ± 1.01, 3.06 ± 1.15 ng/mL (P = 0.419), respectively; 2 pp at baseline was 230.80 ± 64.67 mg/dL, which significantly decreased to 193.15 ± 61.70 mg/dL after treatment with FC decoction; while it was 229.65 ± 70.13 mg/dL after treatment with placebo (P < 0.001). Conclusions: Addition of FC decoction to oral hypoglycemic drugs might significantly decrease 2hpp in patients with DM type 2. It is a safe and inexpensive method. The mechanism for this decrease is something other than increased insulin secretion.

Efficacy and Safety of 2% and 4% Articaine for Lower Third Molar Surgery

This double-blind crossover randomized clinical trial compared the efficacy of 2 concentrations of articaine, 2% (A2) and 4% (A4), with 1:200,000 epinephrine, for lower third molar removal. During 2 separate appointments with either A2 or A4, both similarly positioned lower third molars in 46 volunteers were extracted. The following were evaluated: onset and duration of anesthetic action on soft tissues, intraoperative bleeding, hemodynamic parameters, postoperative analgesia, and mouth opening and wound healing during the 7th postoperative day, along with the incidence, type, and severity of adverse reactions. Nearly identical volumes of both anesthetic solutions were used for each appointment: 3.4 ± 0.9 mL ≈ 68 mg of articaine (A2) and 3.3 ± 0.8 mL ≈ 132 mg of articaine (A4). Statistical analysis indicated no differences in onset or duration of anesthetic action on soft tissues or duration of postoperative analgesia evoked by A2 and A4 anesthetic solutions (P > 0.05). The surgeon’s rating of intraoperative bleeding was considered minimal throughout all surgery with both anesthetic solutions. While transient changes in blood pressure, heart rate, and oxygen saturation were observed, these factors were clinically insignificant and were uninfluenced by articaine concentration (P > 0.05). No systemic or local adverse reactions were observed in the preoperative and postoperative periods due to A2 or A4, but 1 case of bilateral paresthesia was observed. There were no significant differences between preoperative and postoperative (7th day) values of mouth opening and wound healing whether volunteers received A2 or A4 (P > 0.05). In conclusion, both A2 and A4, administered in equal volumes, were effective and safe during lower third molar surgery, and no significant differences were found between their efficacy and safety (ClinicalTrials.gov NCT02457325).

Effects of beta-carotene fortified synbiotic food on metabolic control of patients with type 2 diabetes mellitus: A double-blind randomized cross-over controlled clinical trial

The aim of the present study was to determine the beneficial effects of beta-carotene fortified synbiotic food intake on metabolic status in patients with type 2 diabetes mellitus (T2DM). This randomized double-blinded placebo-controlled crossover clinical trial was conducted among 51 patients with T2DM. Individuals were randomly assigned to take either a beta-carotene fortified synbiotic (n=51) or control food (n=51) for 6 weeks. The beta-carotene fortified synbiotic was containing Lactobacillus sporogenes (1×10(7)CFU), 0.1g inulin and 0.05g beta-carotene. Control food (the same substance without probiotic, inulin and beta-carotene) was packed in identical 9-gpackages. Patients were requested to use the beta-carotene fortified synbiotic and control foods three times a day. Beta-carotene fortified synbiotic food consumption resulted in a significant decrease in insulin (-1.00±7.90 vs.+3.68±6.91 μIU/mL, P=0.002), HOMA-IR (-0.73±3.96 vs.+1.82±vbnm4.09, P=0.002), HOMA-B (-0.52±19.75 vs.+8.71±17.15, P=0.01), triglycerides (-2.86±49.53 vs.+20.14±50.10mg/dL, P=0.02), VLDL-cholesterol levels (-0.57±9.90 vs.+4.03±10.02mg/dL, P=0.02) and total-/HDL-cholesterol ratio (-0.01±1.08 vs.+0.64±0.81, P=0.001) compared to the control food. In addition, beta-carotene fortified synbiotic food consumption led to elevated plasma nitric oxide (NO) (+6.83±16.14 vs. -3.76±16.47μmol/L, P=0.001) and glutathione (GSH) (+36.58±296.71 vs. -92.04±243.05μmol/L, P=0.01). Beta-carotene fortified synbiotic food intake in patients with T2DM for 6 weeks had favorable effects on insulin, HOMA-IR, HOMA-B, triglycerides, VLDL-cholesterol, total-/HDL-cholesterol ratio, NO and GSH levels.

Efficacy and safety of premedication with single dose of oral pregabalin in children with dental anxiety: A randomized double-blind placebo-controlled crossover clinical trial.

Dental anxiety is a relatively frequent problem that can lead to more serious problems such as a child entering a vicious cycle as he/she becomes reluctant to accept the required dental treatments. The aim of this randomized double-blind clinical trial study was to evaluate the anxiolytic and sedative effect of pregabalin in children. Twenty-five children were randomized to a double-blind placebo-controlled crossover clinical trial. Two visits were scheduled for each patient. At the first visit, 75 mg pregabalin or placebo was given randomly, and the alternative was administered at the next visit. Anxiolytic and sedative effects were measured using the visual analogue scale. The child's behavior was rated with the Frankl behavioral rating scale and the sedation level during the dental procedure was scored using the Ramsay sedation scale. The unpaired, two-tailed Student's t-test was used to compare the mean changes of visual analog scale (VAS) for anxiety in the pregabalin group with that of the placebo group. A repeated measures MANOVA model was used to detect differences in sedation level in the pregabalin and placebo groups regarding the interaction of 3-time measurements; sub-group analysis was performed using Student's t-test. The Mann-Whitney U-test was used to analyze the nonparametric data of the Frankl and Ramsay scales. A P < 0.05 was considered significant. The reduction of the VAS-anxiety score from 2 h post-dose was statistically significant in the pregabalin group. From 2 h to 4 h post-dose, the VAS-sedation score increased significantly in the pregabalin group. The child's behavior rating was not significantly different between the groups. The number of "successful" treatment visits was higher in the pregabalin group compared to the placebo group. Significant anxiolytic and sedative effects can be anticipated 2 h after oral administration of pregabalin without serious side effects.

Modafinil Improves Real Driving Performance in Patients with Hypersomnia: A Randomized Double-Blind Placebo-Controlled Crossover Clinical Trial

Patients with excessive daytime sleepiness (EDS) are at high risk for driving accidents, and physicians are concerned by the effect of alerting drugs on driving skills of sleepy patients. No study has up to now investigated the effect of modafinil (a reference drug to treat EDS in patients with hypersomnia) on on-road driving performance of patients suffering from central hypersomnia. The objective is to evaluate in patients with central hypersomnia the effect of a wake-promoting drug on real driving performance and to assess the relationship between objective sleepiness and driving performance. Randomized, crossover, double-blind placebo-controlled trial conducted among 13 patients with narcolepsy and 14 patients with idiopathic hypersomnia. Patients were randomly assigned to receive modafinil (400 mg) or placebo for 5 days prior to the driving test. Each condition was separated by at least 3 weeks of washout. Mean number of Inappropriate Line Crossings, Standard Deviation of Lateral Position of the vehicle and mean sleep latency in the Maintenance of Wakefulness Test were assessed. Modafinil reduced the mean number of Inappropriate Line Crossings and Standard Deviation of Lateral Position of the vehicle compared to placebo (F(1,25) = 4.88, P < 0.05 and F(1,25) = 3.87, P = 0.06 tendency). Mean sleep latency at the Maintenance of Wakefulness Test significantly correlated with the mean number of Inappropriate Line Crossings (r = -0.41, P < 0.001). Modafinil improves driving performance in patients with narcolepsy and idiopathic hypersomnia. The Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to drive in this population.

Rhinix™ Nasal Filters For The Treatment Of Allergic Rhinitis: A Randomized, Double-Blinded Placebo-Controlled Crossover Clinical Trial

RationaleNasal filters might be useful as an alternative to current treatments for seasonal allergic rhinitis. The aim of this study was to evaluate the efficacy, safety and usability of Rhinix™ nasal filters in the treatment of seasonal allergic rhinitis.MethodsThe trial was a single-centre, randomized (1:1), double-blinded placebo-controlled crossover clinical trial (NCT01699165) conducted out of season in an Environmental Exposure Unit (EEU) in Aarhus, Denmark on 24 subjects with proven grass allergy. A total nasal symptom score (TNSS) consisting of nasal congestion, nasal discharge, nasal itching and sneezing was used as the primary outcome measure. TNSS was rated 9 times during each study day and evaluated based on the difference in daily TNSS (the sum of all 9 ratings) and maximum TNSS (the highest score of the 9).ResultsRhinix™ reduced daily TNSS by 21% (P=0.049), daily sneezing by 45% (P=0.01), maximum itching by 46% (P=0.004) and maximum sneezing by 38% (P=0.001) when compared to placebo. Rhinix™ failed to show a significant reduction in the primary efficacy endpoint of difference in maximum TNSS (P=0.14) with a mean reduction of 14% and median reduction of 33% when compared to placebo. The nasal filters were well tolerated and no serious adverse events were recorded.ConclusionsAlthough maximum TNSS showed no statistically significant difference, statistically significant and clinically relevant reductions were achieved with Rhinix™ nasal filters in daily TNSS as well as in a subset of individual symptoms for patients with seasonal allergic rhinitis. RationaleNasal filters might be useful as an alternative to current treatments for seasonal allergic rhinitis. The aim of this study was to evaluate the efficacy, safety and usability of Rhinix™ nasal filters in the treatment of seasonal allergic rhinitis. Nasal filters might be useful as an alternative to current treatments for seasonal allergic rhinitis. The aim of this study was to evaluate the efficacy, safety and usability of Rhinix™ nasal filters in the treatment of seasonal allergic rhinitis. MethodsThe trial was a single-centre, randomized (1:1), double-blinded placebo-controlled crossover clinical trial (NCT01699165) conducted out of season in an Environmental Exposure Unit (EEU) in Aarhus, Denmark on 24 subjects with proven grass allergy. A total nasal symptom score (TNSS) consisting of nasal congestion, nasal discharge, nasal itching and sneezing was used as the primary outcome measure. TNSS was rated 9 times during each study day and evaluated based on the difference in daily TNSS (the sum of all 9 ratings) and maximum TNSS (the highest score of the 9). The trial was a single-centre, randomized (1:1), double-blinded placebo-controlled crossover clinical trial (NCT01699165) conducted out of season in an Environmental Exposure Unit (EEU) in Aarhus, Denmark on 24 subjects with proven grass allergy. A total nasal symptom score (TNSS) consisting of nasal congestion, nasal discharge, nasal itching and sneezing was used as the primary outcome measure. TNSS was rated 9 times during each study day and evaluated based on the difference in daily TNSS (the sum of all 9 ratings) and maximum TNSS (the highest score of the 9). ResultsRhinix™ reduced daily TNSS by 21% (P=0.049), daily sneezing by 45% (P=0.01), maximum itching by 46% (P=0.004) and maximum sneezing by 38% (P=0.001) when compared to placebo. Rhinix™ failed to show a significant reduction in the primary efficacy endpoint of difference in maximum TNSS (P=0.14) with a mean reduction of 14% and median reduction of 33% when compared to placebo. The nasal filters were well tolerated and no serious adverse events were recorded. Rhinix™ reduced daily TNSS by 21% (P=0.049), daily sneezing by 45% (P=0.01), maximum itching by 46% (P=0.004) and maximum sneezing by 38% (P=0.001) when compared to placebo. Rhinix™ failed to show a significant reduction in the primary efficacy endpoint of difference in maximum TNSS (P=0.14) with a mean reduction of 14% and median reduction of 33% when compared to placebo. The nasal filters were well tolerated and no serious adverse events were recorded. ConclusionsAlthough maximum TNSS showed no statistically significant difference, statistically significant and clinically relevant reductions were achieved with Rhinix™ nasal filters in daily TNSS as well as in a subset of individual symptoms for patients with seasonal allergic rhinitis. Although maximum TNSS showed no statistically significant difference, statistically significant and clinically relevant reductions were achieved with Rhinix™ nasal filters in daily TNSS as well as in a subset of individual symptoms for patients with seasonal allergic rhinitis.

The Effect of Rosa Damascena Extract on Primary Dysmenorrhea: A Double-blind Cross-over Clinical Trial

Background:Dysmenorrhea is one of the most common types of cyclic pain that affects 50% of women and girls in their menstrual ages. Because of the side-effects and contraindications of chemical medicines, using herbs has been investigated in treating dysmenorrhea.Objectives:The aim of this study was to determine the effect of Rosa damascena extract on primary dysmenorrhea among the students of Kowsar dormitory in Tabriz University of Medical Sciences.Materials and Methods:This study was performed in Iran on 92 single 18-24 year old students with BMI :19-25 and obtaining pain intensity score of 5-8 in Visual Analogue Scale that were randomly classified and included in two groups of 46 persons. The participants received two capsules of Mefenamic Acid and Rosa damascena with the similar physical properties in two consecutive cycles per 6 hours for 3 days in a cross-over form. The data were collected through the questionnaire of demographic characteristics and check-list of visual analogue scale. Descriptive statistics and repeated measurement test and independent samples t test by using SPSS (13/win) were used in order to determine and compare the effects of two drugs on dysmenorrheal pain intensity of the groups.Results:There was a significant difference between the average of pain intensity at different hours of measurement in each group after the end of first cycle and second cycle (P < 0.001). There was no significant difference between the average of pain intensity in two groups in the first cycle (P = 0.35) and second cycle (P = 0.22).Conclusions:In this study¸ Rosa damascena and Mefenamic acid had similar effects on pain intensity of primary dysmenorrhea . With further studies, Rosa damascena which has no chemical side effects¸ can be suggested for treating primary dysmenorrhea.

A Randomized Crossover Clinical Trial to Evaluate the Efficacy of Oral Transmucosal Fentanyl Citrate in the Treatment of Dyspnea on Exertion in Patients With Advanced Cancer

Morphine is the only opioid which has been clearly demonstrated as effective in the treatment of dyspnea. The role of other opioids has not been sufficiently substantiated. To evaluate the efficacy of oral transmucosal fentanyl citrate (OTFC) in the treatment of dyspnea on exertion in patients with advanced cancer. This is a randomized, double-blind crossover clinical trial to evaluate the efficacy of OTFC in dyspnea on exertion after the completion of a 6-minute walk test (6MWT). All patients were attended in 2011 by the Palliative Care Supportive Team from Badajoz. In visit 1, patients were randomly assigned to 1 of the 2 treatment groups. In visit 2, the patients who had been receiving the investigational product were given placebos and vice versa. Thirteen patients were recruited (26 6MWT), with a mean age of 65 years. Of the patients, 11 (76%)were males and lung cancer was the most frequently represented etiology. The patients were classified into 3e categories: better response in the first period, the same response in both the periods, and better response in the second period. No differences between the treatments were demonstrated (P: 1). There were no differences in changes in oxygen saturation (P: .7541) nor in the distance walked in the different sequences (P: .6550). No significant differences were found in relation to the Edmonton Symptom Assessment System, either before or after the 6MWT (P: .1234). No secondary effects associated with the medication were observed. It could not be demonstrated that the OTFC improved exertion dyspnea in patients with advanced cancer. A placebo effect was observed in all the patients.

Effects of synbiotic food consumption on metabolic status of diabetic patients: A double-blind randomized cross-over controlled clinical trial

We are aware of no study indicating the effects of synbiotic food consumption on metabolic profiles, inflammation and oxidative stress among diabetic patients. The aim of the current study was to investigate the effects of synbiotic food consumption on metabolic profiles, hs-CRP and biomarkers of oxidative stress in diabetic patients. This randomized double-blinded cross-over controlled clinical trial was performed among 62 diabetic patients aged 35-70 y. After a 2-wk run-in period, subjects were randomly assigned to consume either a synbiotic (n = 62) or control food (n = 62) for 6 weeks. A 3-week washout period was applied following which subjects were crossed over to the alternate treatment arm for an additional 6 weeks. The synbiotic food consisted of a probiotic viable and heat-resistant Lactobacillus sporogenes (1 × 10(7) CFU), 0.04 g inulin (HPX) as prebiotic with 0.38 g isomalt, 0.36 g sorbitol and 0.05 g stevia as sweetener per 1 g. Control food (the same substance without probiotic bacteria and prebiotic inulin) was packed in identical 9-gram packages. Patients were asked to consume the synbiotic and control foods three times a day. Fasting blood samples were taken at baseline and after a 6-wk intervention to measure metabolic profiles, hs-CRP and biomarkers of oxidative stress. Consumption of a synbiotic food, compared to the control, resulted in a significant decrease in serum insulin levels (changes from baseline: -1.75 ± 0.60 vs. +0.95 ± 1.09 μIU/mL, P = 0.03). Although we failed to find a significant effect of synbiotic food consumption on total- and LDL-cholesterol levels and HOMA-IR, the effects on FPG (22.3 vs. 4.2 mg/dL, P = 0.09), serum triglycerides (45.9 vs. 20.6 mg/dL, P = 0.08) and HDL-cholesterol levels (3.1 vs. -2 mg/dL, P = 0.06) tended to be significant. A significant reduction in serum hs-CRP levels (-1057.86 ± 283.74 vs. 95.40 ± 385.38 ng/mL, P = 0.01) was found following the consumption of synbiotic food compared with the control group. Supplementation with the synbiotic food led to a significant increase in plasma total GSH (319.98 vs. 19.73 μmol/L, P < 0.001) and serum uric acid levels (+0.7 vs. -0.1 mg/dL, P = 0.04) compared to the control food. No significant effect of the synbiotic food was observed on plasma TAC levels. In conclusion, consumption of a synbiotic food for 6 weeks among diabetic patients had significant effects on serum insulin, hs-CRP, uric acid and plasma total GSH levels. www.irct.ir: IRCT201201195623N1.

Red Grape Seed Extract Improves Lipid Profiles and Decreases Oxidized Low-Density Lipoprotein in Patients with Mild Hyperlipidemia

Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.

Melatonin improves sleep quality in hemodialysis patients

Disturbed sleep is common in end-stage renal disease (ESRD). Exogenous melatonin has somniferous properties in normal subjects and can improve sleep quality (SQ) in several clinical conditions. Recent studies have shown that melatonin may play a role in improving sleep in patients undergoing dialysis. The goal of the present study was to assess the effect of exogenous melatonin administration on SQ improvement in daytime hemodialysis patients. Lipid profile and the required dose of erythropoietin (EPO) are also reported as secondary outcomes. In a 6-week randomized, double-blind cross-over clinical trial, 3 mg melatonin or placebo was administered to 68 patients at bedtime. A 72-h washout preceded the switch from melatonin to placebo, or vice versa. SQ was assessed by the Pittsburgh sleep quality index (PSQI). Sixty-eight patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved the global PSQI scores (P < 0.001), particularly subjective SQ (P < 0.001), sleep efficiency (P = 0.005) and sleep duration (P < 0.001). No differences in sleep latency and daytime sleepiness were observed. Melatonin also increased the high-density lipoprotein (HDL) cholesterol (P = 0.003). The need for EPO prescription decreased after melatonin treatment (P < 0.001). We conclude that melatonin can improve sleep in ESRD. The modest increase in HDL cholesterol and decrease in the EPO requirement are other benefits associated with this treatment

Comparison of the effect of aspirin and amantadine for the treatment of fatigue in multiple sclerosis: a randomized, blinded, crossover study

Objectives: The purpose of this study was to compare the relative efficacy of acetylsalicylic acid (ASA) and amantadine for the treatment of fatigue in multiple sclerosis (MS).Methods: A 10-week, randomized double-blind crossover clinical trial conducted from October 2009 to September 2010. Fifty-two patients with MS presenting fatigue at 21 to 53 years of age were randomly allocated to the two treatment groups. The first group received amantadine (100 mg twice daily) for a total of 4 weeks. The second group received ASA (500 mg once daily) for four weeks. After a 2-week washout period, they crossed over to the alternative treatment for 4 weeks. Patients were rated at baseline and the end of each phase with the Fatigue Severity Scale (FSS).Results: ASA appeared to be equivalent in efficacy and safety to amantadine. A significant decrease in FSS occurred in both groups. Of the 26 patients treated with amantadine, the mean (SD) of FSS decreased from 4·8 (1·4) to 4·0 (1·4) (P<0·001). In the 26 patients treated with ASA, the mean (SD) of FSS decreased from 4·6 (1·4) to 3·5 (1·5) (P<0·001).Discussion: This study demonstrates that both ASA and amantadine significantly reduce MS-related fatigue. Both ASA and amantadine have previously been shown to reduce fatigue, and we postulate that treatment with ASA and amantadine may have similar benefits.

Design of a randomized controlled double-blind crossover clinical trial to assess the effects of saliva substitutes on bovine enamel and dentin in situ

BackgroundHyposalivation is caused by various syndromes, diabetes, drugs, inflammation, infection, or radiotherapy of the salivary glands. Patients with hyposalivation often show an increased caries incidence. Moreover, hyposalivation is frequently accompanied by oral discomfort and impaired oral functions, and saliva substitutes are widely used to alleviate oral symptoms. However, preference of saliva substitutes due to taste, handling, and relief of oral symptoms has been discussed controversially. Some of the marketed products have shown demineralizing effects on dental hard tissues in vitro. This demineralizing potential is attributed to the undersaturation with respect to calcium phosphates. Therefore, it is important to modify the mineralizing potential of saliva substitutes to prevent carious lesions. Thus, the aim of the present study was to evaluate the effects of a possible remineralizing saliva substitute (SN; modified Saliva natura) compared to a demineralizing one (G; Glandosane) on mineral parameters of sound bovine dentin and enamel as well as on artificially demineralized enamel specimens in situ. Moreover, oral well-being after use of each saliva substitute was recorded.Methods/DesignUsing a randomized, double-blind, crossover, phase II/III in situ trial, volunteers with hyposalivation utilize removable dentures containing bovine specimens during the experimental period. The volunteers are divided into two groups, and are required to apply both saliva substitutes for seven weeks each. After both test periods, differences in mineral loss and lesion depth between values before and after exposure are evaluated based on microradiographs. The oral well-being of the volunteers before and after therapy is determined using questionnaires. With respect to the microradiographic analysis, equal mineral losses and lesion depths of enamel and dentin specimens during treatment with SN and G, and no differences in patients' experienced oral comfort after SN compared to G usage are expected (H0).DiscussionUp to now, 14 patients have been included in the study, and no reasons for early termination of the trial have been identified. The design seems suitable for determining the effects of saliva substitutes on dental hard tissues in situ, and should provide detailed information on the oral well-being after use of different saliva substitutes in patients with hyposalivation.Trial registrationClinicalTrials.gov ID. NCT01165970

Evaluating the effect of zingiber officinalis on nausea and vomiting in patients receiving Cisplatin based regimens.

Ginger, the rhizome of Zingiber officinalis, has long been used as herbal medicine for its antiemetic effect. For evaluating the effect of zingiber officinalis on nausea and vomiting (N and V) in patients receiving cisplatin based regimens, a randomized double-blind placebo-controlled cross-over clinical trial was carried out in patients receiving cisplatin in combination with other chemotherapeutic agents. The patients were randomly assigned to receive ginger capsules (rhizome of zingiber officinalis) or placebo in their first cycle of the study. All patients received standard antiemetics for chemotherapy induced nausea and vomiting (CINV). The patients were crossed-over to receive ginger or placebo in their next cycle of chemotherapy. Among 36 eligible patients who received both cycles of treatment, there were no difference in prevalence, severity, and duration of both acute and delayed N and V. Addition of ginger to the standard antiemetic regimen has shown no advantage in reducing acute and delayed N and V in patients with cisplatin-based regimen in this study.

The effect of thymoquinone on intractable pediatric seizures (pilot study)

despite administration of numerous combinations of epileptic drugs, nearly 15% of childhood seizures are resistant to treatment and it is still a problem in pediatric practice. In traditional medicine, Nigella sativa was known to have anticonvulsant effects. Recent studies also have shown its anticonvulsant effects. Most of the properties of N. sativa or its extracts are mainly attributed to thymoquinone. It has been shown that thymoquinone has several therapeutic effects and no evidence of toxicity or side effects is reported. in this pilot, double-blinded crossover clinical trial study on children with refractory epilepsy, thymoquinone with dose of 1mg/kg was administered as an adjunctive therapy and its effects on frequency of seizures were compared with those of a placebo. Twenty-two patients entered in the study. They were assigned in two groups and received either thymoquinone or placebo for a period of four weeks, and then during the two weeks of wash out period, they received only their pre-existing anti-epileptic drugs; then, after cross-overing, they received thymoquinone or placebo for a period of four weeks again. During these periods their effects on seizure frequency were investigated. the reduction of frequency of seizures at the end of first period in comparison with the same period before the study demonstrated a significant difference between two groups (thymoquinone and placebo) (P=0.04). Also reduction of frequency of seizure has shown significant difference between two groups at the end of second period in comparison with end of first period (P=0.02). The parental satisfaction showed significant difference between the two groups at the end of the first period (P=0.03). it can be concluded that thymoquinone has anti-epileptic effects in children with refractory seizures.

Pre‐emptive ibuprofen arginate in third molar surgery: a double‐blind randomized controlled crossover clinical trial

This study evaluated the effectiveness of 400 mg ibuprofen arginate either as a pre-emptive (PRE group) or postoperative (POST group) analgesic using a common dental pain model. A randomized double-blind crossover clinical trial involving a series of consecutive patients admitted for bilateral third molar surgery. Results were analysed according to the self-reported pain score and the pattern of rescue medication taken. The mean pain score ranged from 0.73 to 1.60 for the PRE group and 0.47 to 1.41 for the POST group among 30 included subjects. The mean time point when first rescue medication taken was 7.3 hours and 8.3 hours postoperative, respectively. Nine patients (30 per cent) in the PRE group and 12 patients (40 per cent) in the POST group took no rescue medication. There was no statistically significant difference for all parameters between groups, while a majority (53 per cent) found the drug "good" to "excellent" in both groups. Ibuprofen arginate may be considered effective in reducing surgically induced moderate to severe pain when administered either pre-operatively or postoperatively due to the reported relatively low pain score, less consumption of rescue medication, delayed onset of pain, good number of pain-free patients and a high rating in the global assessment score.