Double-blind Placebo-controlled Randomized Study Research Articles

In the article “Double blind randomized placebocontrolled study of the efficacy and safety of proroxan in the complex therapy of generalized anxiety disorder”

In the article “Double blind randomized placebocontrolled study of the efficacy and safety of proroxan in the complex therapy of generalized anxiety disorder”

(029) Safety and Efficacy of Botulinum Neurotoxin in the Treatment of Erectile Dysfunction Refractory to Phosphodiesterase Inhibitors: Results of a Randomized Controlled Trial

Abstract Introduction There has been recent interest in the use of botulinum neurotoxin (BoNT) in the field of Andrology, whereby it has been investigated in the treatment of penile retraction and premature ejaculation. Objective To evaluate the safety and efficacy of intracavernosal BoNT-A injection in the treatment of patients with erectile dysfunction (ED) refractory to oral phosphodiesterase inhibitors (PDE5Is). Methods A double-blind randomized placebo-controlled prospective comparative study conducted at one center and involved 70 patients with ED refractory to PDE5Is. At baseline, the following data were collected: erection hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), sexual health inventory for men (SHIM), and the sexual encounter profile 2&3 (SEP-2&3) questionnaires. Treatment group (n = 35) received a single ICI of 100 units of BoNT-A in 2 ml of saline and control group (n = 35) received a single ICI of 2 ml of saline. EHS, PSV, and EDV were assessed at 2 weeks post treatment. SHIM, SEP-2, SEP-3, and global assessment questionnaire (GAQ-Q1&Q2) were completed at 2-, 6-, and 12-weeks post treatment. Results Two weeks post treatment, the treatment group showed a statistically significant improvement in the mean EHS, PSV, EDV, and GAQ-Q1 positive responders (p < 0.001) compared to the control group. At 6- and 12-weeks post treatment, the treatment group showed a statistically significant improvement in the SHIM scores, SEP-2, and GAQ-Q1&Q2 positive responders compared to the control group. At 6 weeks, where there was a 5-point improvement in the mean SHIM score of the treatment group (10±5.9 from 5.4±1.7 at baseline) versus no improvement in the placebo group, 18 patients in the treatment group (53%) were able to have an erection hard enough for vaginal penetration versus only one patient in the control group. Conclusions BoNT-A is safe and effective as a potential treatment for ED refractory to PDE5I therapy. Disclosure No.

Double blind randomized placebo-controlled study of the efficacy and safety of proroxan in the complex therapy of generalized anxiety disorder

Introduction. The clinical picture of generalized anxiety disorder is characterized by diffuse anxiety, muscle tension and multiple symptoms of hyperactivity of the sympathetic part of the autonomic nervous system. As an alpha-adrenoblocker, proroxan can reduce the hyperactivity of the autonomic nervous system, thereby reducing the severity of anxiety and its somatic symptoms.Aim. To evaluate the efficacy of proroxan in the correction of autonomic disorders in patients with generalized anxiety disorder compared to placebo.Materials and methods. 100 people participated in the study: 50 – in the study group received the SSRI escitalopram, 50 – in the control group received SSRI + placebo. The diagnosis of generalized anxiety disorder was made on the basis of ICD-10 criteria. Psychometric assessment using the Montgomery-Asberg scale was performed (only at the screening visit). Weekly psychometric evaluation was performed using the Hamilton anxiety scale, the SCL-90-R scale to assess somatic manifestations of anxiety, and general clinical impression scales (CGI-S disease severity and CGI-I general improvement).Results. In the course of the study, statistically significant decrease in the mean value of CGI-S scale was observed in both groups, however, more pronounced in the proroxan group (p > 0.05); in the CGI-I scale, more pronounced improvement was observed in the first week of treatment in the proroxan group (p > 0.05). The HAM-A scale also showed a more significant reduction in anxiety in the proroxan group than in the placebo group (p > 0.05). The SCL-90-R SOM scale showed a decrease in the mean value in both groups, more pronounced in the proroxan group, which confirms the effect of the drug on autonomic symptoms of anxiety (p > 0.05).Conclusions. The obtained results confirm the superiority of combination therapy with escitalopram and proroxan in the treatment of generalized anxiety disorder compared to monotherapy. The advantages of proroxan were the absence of sedative effect and, in general, good tolerability, absence of withdrawal syndrome and control of vegetative manifestations of anxiety.

The effect of zoledronic acid on hip geometry in renal transplant recipients: a double-blind placebo-controlled randomized study

BackgroundIn renal transplant patients, bisphosphonates may prevent bone loss, but little is known about their effects on bone microarchitecture and geometrical hip parameters, as the key factors of bone stability. This study aimed to analyze the effect of zoledronic acid on the mentioned parameters in kidney transplant patients.MethodsIn this double-blind, randomized trial, 33 patients were followed for six months after administering either 4mg of zoledronic acid or a placebo. Bone mineral density (BMD) measurement of the spine, hip, radius, and whole body was obtained, and trabecular bone score (TBS) was evaluated using the software. Geometric assessment at the proximal femur was performed by the HSA program.ResultsEighteen patients in the intervention group and 15 in the control group completed the study. The mean percentages of the changes in the BMD at the lumbar spine and whole body were significantly different between the placebo and intervention groups (-0.23% vs. 4.91% and -2.03% vs. 1.23%) (P < 0.05). Zoledronic acid appeared to enhance the subperiosteal diameter, endocortical diameter, and cross-sectional moment of inertia (CSMI) at the narrow neck in comparison with placebo (P < 0.05); however, no difference in TBS was observed between both groups (P > 0.05).ConclusionsWe concluded that a single administration of zoledronic acid might ameliorate bone loss at the lumbar spine and the whole body and maintain the subperiosteal diameter, endocortical diameter, and CSMI as parameters of bone strength at the narrow neck of the proximal femur after six months in renal-transplant recipients.Trial registrationThis study was registered in IRCT (ID: IRCT20181202041821N1) on 04–05-2019.

The effect of lumbopelvic manipulation on electromyography parameters of gluteus medius and vastus medialis in patients with patellofemoral pain syndrome: A double-blind, placebo-controlled trial

BackgroundPatellofemoral Pain Syndrome is the most common cause of anterior knee pain, especially in active young people. This study aimed to evaluate the effect of lumbopelvic manipulation on electromyography parameters of gluteus medius and vastus medialis in patients with patellofemoral pain syndrome. MethodsIn this double-blind placebo-controlled randomized clinical trial study, 26 patients with a diagnosis of patellofemoral pain syndrome were randomly divided into two groups. The first group received Lumbopelvic manipulation and the second group was a control group that received placebo manipulation. Electromyography activity of vastus medialis and gluteus medius muscles were evaluated as primary outcomes during the single-leg squat; pain intensity during rest and functional tasks (step up, step down, single leg squat) were assessed by numerical pain rating scale. Functional status was evaluated by step-down test and the score of the Kujala patellofemoral questionnaire, as secondary outcomes. All evaluations were performed before and after the intervention, except pain intensity at rest and the Kujala patellofemoral questionnaire that were assessed before the intervention and one week after. ResultIn both groups, no significant difference was observed before and after the intervention in terms of average amplitude and the onset of gluteus medius and vastus medialis. However, in the lumbopelvic manipulation group, pain intensity during rest and functional tests significantly decreased compared to the control group. Functional status significantly improved in the lumbopelvic manipulation group, with no significant difference between group comparisons. ConclusionLumbopelvic manipulation caused a reduction in pain intensity and improvement of functional status in the rehabilitation of patients with patellofemoral Pain Syndrome. However, it seems that this method could not change the EMG activity of muscles in these patients. Implications for practice•The results of present study can help physiotherapists to understand the possible underlying pathomechanics of patellofemoral pain syndrome and more effective treatment of these group of patients.

Study protocol of a multicentre double-blind RCT, comparing a traditional RCT with an aggregated N-of-1 trial: GAG therapy Efficacy Trial Solution for Bladder pain syndrome/Interstitial cystitis (GETSBI study)

IntroductionObtaining level 1 evidence on efficacy of glycosaminoglycan (GAG) therapy is difficult, due to low incidence of bladder pain syndrome/interstitial cystitis (BPS/IC) and heterogeneous symptoms experienced by patients with BPS/IC....

Oral 24-week probiotics supplementation did not decrease cardiovascular risk markers in patients with biopsy proven NASH: A double-blind placebo-controlled randomized study

Introduction and ObjectivesCardiovascular disease (CVD) is the major cause of death in non-alcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Probiotics are often indicated for the disease, but their results are controversial in part due to the poor quality of studies. Thus, we investigated the impact of 24-week probiotics supplementation on cardiovascular risk (CVR) in biopsy-proven non-alcoholic steatohepatitis (NASH) patients. Patients and MethodsDouble-blind, placebo-controlled, single-center study (NCT03467282), adult NASH, randomized for 24 weeks daily sachets of probiotic mix (109CFU of Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus paracasei and Bifidobacterium lactis) or placebo. Clinical scores (atherogenic indexes, atherosclerotic cardiovascular disease-ASCVD and systematic coronary risk evaluation-SCORE), biochemistry, miR-122, miR-33a, plasminogen activator inhibitor-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), were determined before and after the intervention. ResultsForty-six patients were enrolled (23 received probiotics and 23 placebo), with a mean age of 51.7 years, most of them females and whites. Clinical and demographic features were similar between the groups at the baseline. The Median NAFLD activity score was 4.13 in both groups. Fibrosis was mild in most patients (15.2% and 65.2% F0 and F1, respectively). Treatment did not promote any clinically significant changes in body mass index or laboratory, including lipid and glucose profile. High CVR patients through atherogenic indexes decreased from baseline in both groups, as well as PAI-1 and miR-122 levels, although there was no difference between probiotics and placebo. ConclusionsA 24-week probiotic mix administration was not superior to placebo in reducing CVR markers in patients with NASH.

Topical issues of prevention of stomach cancer: A review

Prevention of gastric cancer, both primary and secondary, is an extremely important component of the management of gastroenterological patients. The correct collection of anamnesis with an assessment of the hereditary (family) cancer risk, the action of risk factors (eating disorders, habitual/chronic intoxication, obesity, Helicobacter pylori infection, etc.), as well as the use of gastroprotectors (in particular, the drug Regastim Gastro), especially in persons with potentially precancerous the condition is chronic atrophic gastritis. According to the data of a double-blind placebo-controlled randomized study Regastim Gastro (active ingredient alpha-glutamyl tryptophan) in the treatment of chronic atrophic gastritis, it was found that this drug has a powerful anti-inflammatory effect and regenerative activity. Taking the drug Regastim Gastro, compared with placebo, statistically significantly contributed to a decrease in the number of inflammatory infiltration cells per 1 mm2 of the gastric mucosa. Regastim Gastro decreases in eosinophilic (3 times) and neutrophilic (4 times) infiltration of the gastric mucosa and also reduced the number of macrophages, lymphocytes and plasmocytes. In addition to anti-inflammatory properties, the drug also had a pronounced regenerative effect. Taking of Regastim Gastro statistically significant (p=0.028) increases in the number of glands per 1 mm2 of the gastric mucosa by 26.1% compared with the initial screening indicators. In the group of patients taking placebo, on the contrary, there was a further progression of the pathological process, accompanied by a decrease in the number of glands per 1 mm2 of the gastric mucosa after the end of treatment in comparison with the initial indicators. After the course of therapy, the number of glands per 1 mm2 of the gastric mucosa in patients taking the drug Regastim Gastro was statistically significantly higher in comparison with the results in the placebo group (p=0.013). After the course of Regastim Gastro, there was an improvement in acid production: a shift in the acidic side of the average pH value (1.6 times) and an increase in the value of the acidity index, both when compared with the initial values (5.4 times) and in comparison with the placebo group (2.9 times). The intake of Regastim Gastro to patients with gastritis, both H. pylori (+) and H. pylori (-) before the development of atrophy of the gastric mucosa can reduce the inflammatory factor, prevent the occurrence of atrophy and may have maximum anti-carcinogenic action.

Enigmatic Neural Pathways: Potentiating Viral Neuroinvasion Into the CNS.

Enigmatic Neural Pathways: Potentiating Viral Neuroinvasion Into the CNS.

Changes in Electrical Brain Activity Due to tDCS in Post-Stroke Chronic Aphasia: a Double-Blind Randomized Controlled Study

<h3>Research Objectives</h3> To better understand changes in brain activity related to transcranial direct current stimulation (tDCS) in post-stroke chronic aphasia. <h3>Design</h3> Double-blind randomized placebo controlled study design. <h3>Setting</h3> Casa Colina Research Institute. <h3>Participants</h3> Forty three post-stroke outpatients with chronic aphasia (32 males; age: 61±13y; 0.9-18years post-injury; 32 ischemic stroke; 19 non-fluent aphasia). Twenty patients were in the tDCS group. <h3>Interventions</h3> Participants were randomly assigned either to the tDCS group (cathode on Broca, left side) or to the sham/placebo group. Both groups had five consecutive days of 20 minutes session, using a FDA approved tDCS device (soterixmedical.com). Resting state electrophysiological recordings (5 minutes) and behavioral assessments were performed the week before/after tDCS/sham intervention. <h3>Main Outcome Measures</h3> 1) EEG data: power spectrum as well as coherence in delta, theta, alpha and beta frequencies in fronto-temporal electrodes; 2) Behavioral data: the Western Aphasia Battery-Revised (WAB-R total scores and subscores). <h3>Results</h3> For the behavioral data, groups differed, pre/post intervention, on the WAB-R total score (F=5.22; p=0.028) as well as for the Auditory-Verbal Comprehension (F=4.657; p=0.038) and Repetition (F=4.56; p=0.04) subscores. For the EEG, groups also differed, pre/post intervention, when looking at changes in coherence between Broca and Wernicke on the contralateral side (F8T4, alpha and beta) as well as between Broca area on bilateral sides (F7F8, beta) and other fronto-temporal electrodes (F3T3, beta; FzT5, alpha; F4T5, beta). Post-hoc analyses revealed a significant increase in coherence for the tDCS group (but not for the sham group) for the following electrodes: F8T4 (alpha), F3T3 (beta) and F4T5 (beta). <h3>Conclusions</h3> In this double-blind randomized placebo controlled trial, our findings show a higher improvement in language functions (for both receptive and expressive language skills) in response to treatment as compared to sham. These improvements seem related to an increase in coherence not only in ipsilateral but also contralateral fronto-temporal electrodes, suggesting a higher functional connectivity within the language network due to tDCS in post-stroke chronic aphasia. <h3>Author(s) Disclosures</h3> The authors have nothing to declare.

Prevention of radiotherapy induced enteropathy by probiotics (PREP): protocol for a double-blind randomized placebo-controlled trial

BackgroundRadiation induced enteropathy is a common complication of radiotherapy for pelvic tumors and adversely affects patient quality of life. Probiotics are thought to restore bowel microflora to optimal levels and reinforce intestinal barrier capacity. Although probiotics are effective in the treatment of radiation induced enteropathy, less is known about their efficacy to prevent radiation induced enteropathy.MethodsThis double-blind randomized placebo-controlled study will investigate the efficacy of probiotics to prevent radiation-induced enteropathy in patients with gynecologic or urologic cancer who received pelvic radiotherapy. The study is designed to enroll 248 eligible patients, who will be randomized 1:1 to a probiotic or placebo group. Toxicities will be evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v5.0.DiscussionThe primary aim of this study is to provide high level evidence for the ability of probiotics to prevent acute radiation induced enteropathy. The secondary aims are to determine the effects of probiotics on the incidence of chronic radiation induced enteropathy and the safety of probiotics in patients with gynecologic or urologic cancer.Trial registrationClinicalTrials.gov (NCT03978949, Registered on 7 June 2019).

The effect of Cornus mas extract consumption on bone biomarkers and inflammation in postmenopausal women: A randomized clinical trial.

The drastic decrease in estrogen levels in menopausal women can elevate bone resorption and osteoporosis. Cornus mas extract (C. mas extract) is a potential candidate for treating menopausal-related bone complications because of its phytoestrogen and anti-inflammatory contents. It was an interventional double-blind placebo-controlled randomized study. Eighty-four women aged 45-60 years old were randomly allocated to either the extract group receiving 3 capsules of 300 mg C. mas extract or the placebo group receiving 3 capsules of 300 mg of starch powder per day for 8 weeks. Then, venous blood was used to measure bone-specific alkaline phosphatase (BAP), osteocalcin (OC), C-terminal telopeptide (TC) as well as serum levels of PTH and hsCRP. Our results indicated the decrease in alkaline phosphatase, PTH, and as an inflammation biomarker, hsCRP, between two groups at the end of the study. No statistically significant difference was observed in telopeptide C, osteocalcin, and calcium between the placebo and extract groups after 8 weeks of intervention. In conclusion, the results indicate that the C. mas extract supplement of 900 mg/day may decrease levels of BAP, PTH, and hsCRP. However, this intervention had no beneficial effect on OC and TC in healthy postmenopausal women.

Efficacy and safety of weekly vitamin D3 in patients with fibromyalgia: 12-week, double-blind, randomized, controlled placebo trial.

FM is a chronic musculoskeletal disorder characterized by the presence of generalized pain. There are contradictory results regarding the prevalence and supplementation effect of vitamin D deficiency on FM patients. We aim to determine the safety and efficacy of a 12-week vitamin D supplementation on FM patients. We conducted a randomized, placebo-controlled, double-blind clinical trial. We included female participants of 18 years old or older, who met 1990 or 2010 ACR criteria for fibromyalgia. The Spanish validated FIQ and the VAS of pain were applied at baseline. The participants were then randomized to receive placebo or 50,000 IU of Vitamin D3 PO, weekly for 12 weeks. We included 80 patients. There was no statistical difference in the initial and final FIQ between both groups. The FIQ delta also did not prove to be different at the end of the study. The increase in vitamin D levels in the intervention group was corroborated. Regarding serious adverse effects, none was reported in both groups. There was no statistical difference in minor adverse events. In this double-blind placebo-controlled randomized study conducted to measure the efficacy and safety of vitamin D exclusively in patients with FM, we found that there is no evidence of a trend in favor of vitamin D treatment, since we did not observe improvement in the VAS of pain or FIQ. Clinical Trials.gov number: NCT03369379 Key Points • There are conflicting results in vitamin D to treat fibromyalgia. • In this double-blind, randomized controlled trial, we did not find a difference in the VAS nor FIQ with vitamin D supplementation. • The increase in vitamin D levels in the intervention group was corroborated.

P.326 Efficacy of resveratrol in the treatment of unipolar depression: double-blind randomized placebo-controlled parallel-group study

An enhanced vasoconstrictor activity of cutaneous arteries participates in the reduction of skin blood flow induced by cooling stimulation. Raynaud's phenomenon, which is characterized by intense cooling-induced constriction of cutaneous arteries, is more common in women during the period from menarche to menopause. We thus investigated the effect of 17β-estradiol (E2) on cooling-induced reduction of plantar skin blood flow (PSBF) in mouse in vivo. Ovariectomized female ddY mice, anaesthetized with pentobarbital, were treated with tetrodotoxin for eliminating the sympathetic nerve tone and artificially ventilated. The PSBF was measured by laser Doppler flowmetry. Cooling air temperature around the foot from 25 to 20, 15, or 10 °C decreased the PSBF in a temperature-dependent manner, which was suppressed by the specific α2C-adrenoceptor antagonist MK-912. When E2 was intravenously administered as a bolus followed by a constant infusion for 10 min just before the cooling stimulation, the cooling-induced reduction of PSBF was facilitated by E2 in a dose-dependent manner. The facilitatory effect of E2 was not induced after the treatment with MK-912. Similar facilitatory effect was induced by an intravenous application of G-1, an agonist of G protein-coupled estrogen receptor (GPER, also termed GPR30). Moreover, the facilitatory effect of E2 was abolished by the GPER antagonist G15. These results suggest that acute administration of E2 leads to the facilitation of cooling-induced, α2C-adrenoceptor-mediated reduction of skin blood flow via the activation of the non-genomic estrogen receptor GPER.

Probiotics Supplementation on Cardiac Remodeling Following Myocardial Infarction: a Single-Center Double-Blind Clinical Study

Adverse cardiac remodeling after myocardial infarction (MI) can lead to the syndrome of heart failure (HF). Recently, changes in gut microbiota composition (dysbiosis) have appeared as a novel candidate that may be linked to the development of CR and HF. The aim of this trial was to evaluate the effects of probiotics administration on attenuating CR in patients with MI. A single-center double-blind placebo-controlled stratified randomized clinical study was conducted in 44 subjects with MI who underwent percutaneous coronary intervention (PCI). Patients were randomly assigned to take, with lunch, either a probiotic capsule containing 1.6 × 109 colony-forming unit (CFU) of bacteria (treatment group) or capsules contained inulin (control group) over 3months. CR biomarkers (including serum procollagen III, transforming growth factor beta (TGF-β), trimethylamine N-oxide (TMAO), and matrix metallopeptidase 9 (MMP-9)) were assessed. Echocardiography results were measured at baseline and after the intervention. Significant decreases were seen in serum TGF-β concentrations (- 8.0 ± 2.1 vs. - 4.01 ± 1.8pg/mL, p = 0.001) and TMAO levels (- 17.43 ± 10.20 vs. - 4.54 ± 8.7mmol/L, p = 0.043), and there were no differences were seen in MMP-9 (- 4.1 ± 0.12 vs. - 4.01 + 0.15nmol/mL, p = 0.443) and procollagen III levels (- 1.35 ± 0.70 vs. 0.01 + 0.3mg/L, p = 0.392) subsequent to probiotics supplementation compared with the placebo group. Improvements in echocardiographic indices were also greater in the probiotics group as compared with that in the control group, but not at a significant level. Regression analysis revealed that baseline left ventricular ejection fraction (LVEF), and changes of procollagen III, predicted 62% of the final LVEF levels. Probiotics administration may have a beneficial effect on the cardiac remodeling process in patients with myocardial infarction. Iranian Registry of Clinical Trials (IRCT): IRCT20121028011288N15.

Uric Acid Lowering and Biomarkers of Kidney Damage in CKD Stage 3: A Post Hoc Analysis of a Randomized Clinical Trial

Rationale & ObjectiveHyperuricemia is associated with chronic kidney disease (CKD) progression. We evaluated whether lowering serum uric acid levels improves levels of biomarkers of kidney damage.Study DesignPost hoc analysis of clinical trial participants.Setting & ParticipantsA double-blind randomized placebo-controlled study designed to lower serum uric acid levels. 80 patients with stage 3 CKD and asymptomatic hyperuricemia were randomly assigned to allopurinol treatment or placebo (300 mg/d) for 12 weeks.Exposure/PredictorAllopurinol treatment versus placebo.Outcomes & MeasuresWe evaluated the change from baseline for the following urinary biomarkers of kidney damage: albumin-creatinine ratio (ACR), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), and transforming growth factor β1 (TGF-β1). Additionally, we evaluated CKD Epidemiology Collaboration (CKD-EPI)-estimated glomerular filtration rate (eGFR) and cystatin C eGFR.Analytical ApproachGeneralized linear mixed modeling was used.ResultsAfter 12 weeks, allopurinol (compared to placebo) significantly lowered serum uric acid levels with an estimate of −3.3 mg/dL (95% CI, −4.1 to −2.5 mg/dL; P < 0.001). Estimates for the change for allopurinol versus placebo over time were 1.09 (95% CI, 0.77-1.54) for ACR, 0.77 (95% CI, 0.36-1.63) for NGAL, and 2.36 (95% CI, 0.97-5.70) for TGF-β1. The model did not converge for KIM-1, but Wilcoxon signed rank test showed no significant difference in change from baseline between study groups. There was no significant change observed in CKD-EPI eGFR or cystatin C eGFR.LimitationsPost hoc analysis and short duration of the study.ConclusionsUric acid–lowering with allopurinol is not associated with improvement in levels of biomarkers of kidney damage in patients with asymptomatic hyperuricemia and stage 3 CKD.FundingThe study was funded by the National Institutes of Health through a career development award, K23DK088833, and the Clinical and Translational Science Award UL1TR002537.Trial RegistrationNCT01228903.

Developmental disorders of academic skills in children: the efficacy and safety of Tenoten for children in the multicenter double-blind placebo-controlled randomized study

To evaluate the efficacy and safety of tenoten for children in the treatment of specific developmental disorders of academic skills in children of 1-3 grades. Two hundred and forty children, aged 7-9 years, (Total set, Safety population) with verified specific reading disorder (F81.0), specific spelling disorder (F81.1), specific disorder of arithmetical skills (F81.2), mixed disorder of scholastic skills (F81.3; F81.2+F81.0, or F81.2+F81.1, or F81.2+F81.0+F81.1), diagnosed with the use of logopedic or psychological testing (15-35 scores in Fotekova T.A. and Akhutina T.V. reading and writing tests; 5-15 scores in arithmetical subscale of the Wechsler Intelligence Scale for Children) were enrolled in the study. CT was conducted in 10 clinical centers in Russian Federation in 2015- 2019. Patients were randomized into two groups. The first one (n=122) received tenoten for children in a dose of 1 tablet 3 times a day, the second one (n=118) was administered placebo in the same dosage regimen. The clinical data on 237 children (121 of the tenoten group and 116 of the placebo group) were used for Intention-to-treat efficacy analysis. Data on 220 children (115 of the tenoten group and 105 of the placebo group) were included in Per-protocol analysis. The duration of study was 12 weeks. The mean total academic skills (reading, spelling, and counting) score in groups after 12 weeks of treatment was set as the primary efficacy endpoint. The mean total academic skills score increased by 18.55±15.87 points. The significant total difference between the median changes in the total score in the tenoten and placebo groups was 5 points. There was a trend towards positive changes in reading and spelling mean scores in tests that didn't reach statistical significance due to lack of normal distribution of points in samples. There were 73 adverse events (AEs) in 42 patients of the tenoten group and 95 AEs in 31 children of the placebo group. No serious or severe AEs were registered in the tenoten group. No AEs definitely related to the study treatment were registered. No negative drug interactions were observed in the tenoten group. Tenoten for children is an effective and safe treatment for specific developmental disorders of academic skills in primary school children. Tenoten for children is well tolerated. The treatment is characterized by a high level of adherence of children and their parents to therapy.

Effect of topiramate on eating behaviours in Prader-Willi syndrome: TOPRADER double-blind randomised placebo-controlled study

Prader–Willi Syndrome (PWS) is a rare genetic syndrome leading to severe behavioural disorders and mild cognitive impairment. The objective of this double-blind randomised placebo-controlled trial was to study the efficacy and tolerance of topiramate on behavioural disorders in patients with PWS. Participants (aged 12–45 years) had genetically confirmed PWS and severe irritability/impulsivity, eating disorders and/or obesity, and skin picking. Thirty-two participants received a placebo (PBO), and 30 participants received topiramate (TOP) (50–200 mg/day) for 8 weeks. The primary outcome was the rate of responders using the Clinical Global Impression-Improvement (CGI-I) scale. The secondary outcome measures included the Aberrant Behaviour Checklist, the Dykens Hyperphagia Questionnaire (DHK), the Self-Injurious Behaviour Scale (SIBS) and the body mass index (BMI). We found no significant difference in the primary outcome (the CGI-I): 9 (30%) patients were very much or much improved in the TOP group compared to 7 (22.6%) patients in the PBO group. However, the DHK behaviour and severity scores improved significantly more over time in patients treated with topiramate versus those receiving a placebo, with a significant dose–effect relationship. DHK scores were also significantly associated with genetic subtypes and hospitalisation status. The effects of topiramate on eating behaviours remained significant after adjusting for genetic subtype and hospitalisation. Topiramate had therefore a significant effect on eating disorders, with a dose–effect relationship. Given the burden of eating disorders in PWS, we believe that topiramate may become the first psychotropic option within the global care of obesity in individuals with PWS.

High Effective of 14-Day High-Dose PPI- Bismuth-Containing Quadruple Therapy with Probiotics Supplement for Helicobacter Pylori Eradication: A Double Blinded-Randomized Placebo-Controlled Study.

Background: Helicobacter pylori (H. pylori) infection is important risk factors for chronic gastritis, peptic ulcer and gastric cancer. Bismuth-containing quadruple therapy has recently been the first-line regimen recommended in many European countries but has limited efficacy in ASEAN especially Thailand. This study was aim to evaluate efficacy of high dose PPI Bismuth-containing quadruple therapy with probiotics supplement for H. pylori eradication. Methods:In this double-blind randomized placebo-controlled study, H. pylori infected patients were randomized to receive 7-or 14-day high dose PPI- bismuth-containing quadruple therapy with or without probiotics supplement. Probiotic was 37.5 mg Lactobacillus reuteri (Biogaia®) in tablet twice daily. CYP2C19 genotyping and antibiotic susceptibility tests were also done. H. pylori eradication was defined as a negative 13C-urea breath test at least 4 weeks after treatment. Results:100 subjects were enrolled (72 females, 28 males, mean age=54 years). Antibiotic resistance was 15.6% for clarithromycin, 34.1% for metronidazole. CYP2C19 genotyping was performed in both group and revealed 13%, 50% and 37% for poor, intermediate and rapid metabolizers, respectively. Overall eradication rates of 7-day and 14-day regimens with probiotic were 68% and 96%; P value=0.027. The eradication rate for all patients with poor and rapid metabolizers were 100% with 14-day regimen. 14-day regimen with probiotics can provide 100% eradication with clarithromycin resistance, metronidazole resistance or dual clarithromycin and metronidazole resistance group. Furthermore, the incidence of nausea and vomiting, abdominal discomfort, and bitter taste were significantly lower in patients with probiotics group compared with placebo (6%vs.26%, P=0.002,OR=0.126,95% CI=0.03-0.53; 4%vs.18.0%, P=0.017, OR= 0.155,95% CI=0.03-0.81 and 4%vs.26%, P= 0.001,OR= 0.08, 95%CI= 0.016-0.41, respectively). Conclusions:The 14-day high dose PPI- bismuth-containing quadruple therapy with probiotic can provide an excellent cure rate for H. pylori infection as first line treatment irrespective of CYP2C19 and antibiotic resistance pattern. Adding probiotic also significantly reduced treatment-related adverse events and improve the patients’ compliance.

A phase III double-blind placebo-controlled randomized study of dexamphetamine sulfate for fatigue in primary brain tumors patients: An ANOCEF trial (DXA).

BackgroundMost patients suffering from a primary brain tumor (PBT) complain of chronic fatigue affecting their quality of life (QOL). We hypothesized that dexamphetamine sulfate, a psychostimulant drug, could improve fatigue in PBT patients.MethodsA double-blind, phase III, multi-institutional, placebo-controlled randomized trial (1:1 allocation) assessed the efficacy and tolerability of dexamphetamine at a dosage of 30 mg/day in PBT patients with stable disease who complained of severe fatigue, defined as a Multidimensional Fatigue Inventory (MFI-20) score ≥60. The primary outcome was the variation of the MFI 20 score between inclusion and the evaluation at 3 months in nonprogressive patients. Mood, QOL and cognitive function were also evaluated.ResultsFrom April 2013 to November 2016, 46 patients were enrolled in the study, 41 of whom were evaluable for analysis (dexamphetamine group: 22; placebo group: 19). Tolerance was generally good, with no treatment-related deaths and no grade 4 toxicity. Patients in the dexamphetamine arm complained more frequently of psychiatric side effects (mostly hyperactivity, anxiety, sleep disorder, and irritability) than patients in the placebo arm (P = .018). There were no statistically significant differences at 3 months between the dexamphetamine and placebo arms in any of the outcomes (MFI-20, Norris Visual Analog Scale, Hospital Anxiety and Depression Scale (HADS), QOL (EORTC QLQ-C30/BN 20), Marin’s Apathy Evaluation Scale, and cognitive evaluations).ConclusionDexamphetamine at a dosage of up to 30 mg/day for 3 months has acceptable tolerability in PBT patients but does not improve fatigue, cognitive function, or QOL.