Double-blind Placebo-controlled Randomized Clinical Trial Research Articles

The Effect of L-Citrulline Supplementation on Outcomes of Critically Ill Patients under Mechanical Ventilation; a Double-Blind Randomized Controlled Trial.

Effective parenteral and enteral amino acid replacement is crucial for critically ill patients with altered amino acid metabolism. This study aimed to assess the effects of l-citrulline supplementation on the clinical and laboratory outcomes in critically patients. This was a double-blind placebo-controlled randomized clinical trial. 82 critically ill patients who were expected to receive mechanical ventilation for more than 72 hours were selected. The patients were assigned to either a placebo or an intervention group. The patients in the placebo group received 10 gr of microcrystalline cellulose and the ones in the intervention group were given l-citrulline daily for 7 days. Serum levels of fasting blood sugar (FBS), lipid profile, hepatic enzymes, serum electrolytes, urea nitrogen, creatinine, and C-reactive protein (CRP) were evaluated before and after the intervention. Duration of invasive ventilation, intensive care unit (ICU) length of stay, ventilator-free days, and 28-day mortality rate were recorded and compared between groups. Eighty-two patients completed the trial. No statistically significant differences were observed between the two groups in terms of age (p = 0.46), sex (p = 0.49), body mass index (BMI) (p = 0.41), Sequential Organ Failure Assessment (SOFA) Score (p = 0.08), Clinical Pulmonary Infection Score (CPIS) score (p = 0.76), Acute Physiology and Chronic Health Evaluation (APACHE II) score (p = 0.58), risk factors (p = 0.13), ICU stay before randomization (p = 0.32), and reason of admission (p = 0.50) before the intervention. Citrulline group had a notable reduction in FBS (p = 0.04), total cholesterol (TC) (p = 0.02), low density lipoprotein (LDL-C) (p <0.001) and high-sensitivity CRP (hs-CRP) (p <0.001). Also, a significant increase in lactate dehydrogenase (LDH) concentration (p <0.001) was observed in the intervention group at the end of the trial. Total duration of invasive ventilation and the mean SOFA score on 7th day were significantly lower in the citrulline group compared to the control group. Moreover, a significant increase in days alive and ventilator-free days within 28 days after admission was found in the citrulline group at the end of the trial. Also, there were no significant differences between the groups in terms of mortality rate during intervention, serious adverse events, endotracheal intubation, the use of tracheotomy or non-invasive ventilation after extubation, length of ICU stay, ICU-free days at 28 days, and CPIS and APACHE II scores. For mortality, in the citrulline group, there was two deaths compared to eight deaths in the control group. This resulted in an absolute risk reduction (ARR) of 14.05% (95% CI: 0.39-27.71%) and a number needed to treat (NNT) of 7.1 (95% CI: 3.6-29.5), regarding mortality. The results of the present study demonstrated the probable positive effects of citrulline supplementation on lipid profile, hs-CRP levels, duration of invasive ventilation, and SOFA score. Also, l-citrulline consumption may increase the probability of survival without mechanical ventilation.

Potential lipid-lowering effects of Ulmus macrocarpa Hance extract in adults with untreated high low-density lipoprotein cholesterol concentrations: A randomized double-blind placebo-controlled trial.

Ulmus macrocarpa Hance extract (UME) has demonstrated an antilipidemic effect via upregulation of the adenosine monophosphate-activated protein kinase pathway and regulation of lipid metabolism in both laboratory and animal studies. Therefore, we examined the effects and safety of UME on plasma lipids in adults with untreated high, low-density lipoprotein cholesterol (LDL-C) concentrations. In the current double-blind placebo-controlled randomized clinical trial, 80 patients with untreated high LDL-C concentrations (130-190 mg/dl) were randomly allocated to either the "UME group" (received 500 mg UME as two capsules per day) or the "Placebo group" (received placebo containing cornstarch as two capsules per day) for 12 weeks. The primary outcome was the change in LDL-C concentration within the 12-week treatment period; secondary outcomes included changes in total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B (ApoB) concentrations. UME over 12 weeks led to a greater decrease in LDL-C, TC, and ApoB concentrations than did the placebo as follows: by 18.1 mg/dl (P < 0.001); 23.3 mg/dl (P < 0.001); 9.3 mg/dl (P = 0.018), respectively. When LDL-C, TC, and ApoB concentrations were expressed as a lsmeans percentage of the baseline concentration, they after 12 weeks of UME had greater % differences compared to the placebo as follows: by 11.9% (P < 0.001); 10.0% (P < 0.001); 8.6% (P < 0.05), respectively. However, no significant inter- and intra-group changes in liver enzyme, free fatty acid, anti-inflammatory marker, and fasting glucose concentrations were observed. None of the participants experienced notable adverse events. UME causes a significant improvement in lipid profiles in adults with untreated high LDL-C concentrations. [www.clinicaltrials.gov/], identifier [NCT03773315].

Effect of oral magnesium supplement on cardiometabolic markers in people with prediabetes: a double blind randomized controlled clinical trial

To evaluate the effect of magnesium supplementation on insulin resistance and cardiovascular markers in people with prediabetes. A 12 week double-blind placebo-controlled randomized clinical trial was conducted at Isfahan Endocrine and Metabolism Research Center, Iran, on people with prediabetes (n = 86) to compare the effects of magnesium oxide 250 mg/day versus a placebo on anthropometric indices, blood pressure, fasting glucose, insulin, HOMA-IR index, C-reactive protein, uric acid and lipid profile. Both groups had similar distributions of anthropometric and biochemical variables at baseline. Those who received magnesium supplementation had significantly higher levels of HDL-cholesterol compared to the placebo group at the end of the study (49.7 ± 10.9 vs 43.6 ± 7.2 mg/dL, P = 0.003). The mean changes of HOMA-IR index, total cholesterol, LDL-cholesterol, triglyceride, uric acid and C-reactive protein levels as well as anthropometric indices and blood pressure in supplemented and placebo groups did not differ significantly. Magnesium supplementation increased HDL-cholesterol levels in people with prediabetes. However, other cardiometabolic markers were not improved by magnesium supplementation at the above dosage and duration.

Effect of perioperative COX-2 and beta-adrenergic inhibition on 5-year disease-free-survival in colorectal cancer: A pilot randomized controlled Colorectal Metastasis PreventIon Trial (COMPIT)

IntroductionBased on translational and epidemiological evidence, perioperative inhibition of beta-adrenergic and COX2 signaling can reduce the risk for post-surgical metastatic disease. Here we aimed to assess in a pilot study the impact of a perioperative combined COX-2 and beta-adrenergic blockade on long-term cancer outcomes in colorectal cancer patients undergoing curative surgery. Materials and methodsThirty-four newly diagnosed colorectal cancer patients without evidence of metastases enrolled in this double-blinded placebo-controlled randomized clinical trial (treatment, n = 16; placebo, n = 18). A 20-day oral treatment of propranolol and etodolac regimen was initiated 5 days before surgery. Beneficial effects on short-term molecular biomarkers of cancer progression were reported earlier. Here we present outcomes of five postoperative years of disease-free-survival and overall survival. ResultsAdverse event rates were equivalent between the two groups. Intent-to-treat analyses of 5-year follow-up showed that 2/16 (12.5%) vs 9/18 (50%) patients exhibited recurrence in treatment vs placebo groups, respectively (p = 0.033), and 2/16 (12.5%) vs 4/18 (22%) died (p = 0.467). In protocol compliant patients 0/11 (0%) vs. 8/17 (47%) exhibited recurrence in treatment vs. placebo groups, respectively (p = 0.007), and 0/11 (0%) and 3/17 (17.6%) died (p = 0.151). ConclusionsIn this pilot clinical trial, a combined perioperative treatment with propranolol and etodolac significantly improved 5-year disease-free-survival. The small sample size and a single center study design merits caution in interpreting these results, specifically in estimating the effect-size. Larger studies in colorectal cancer are warranted and needed.

1294TiP Olanzapine for anorexia in cancer cachexia patients: A placebo-controlled randomized trial

Cancer-associated cachexia (CAC) is a complex multifactorial syndrome. Various antipsychotics have been associated with weight gain, especially olanzapine (OLZ) which is suggested to have a role in the management of CAC. It remains unclear whether OLZ has an ameliorating effect on cancer patients’ anorexia, even when those patients exhibit no nausea or vomiting. Given the potential effect of OLZ on CAC and the mixed findings regarding this subject, the current trial aims at evaluating the efficacy of OLZ as a monotherapy in incurable cancer patients with cancer cachexia-associated anorexia. This is a single institution double-blind placebo-controlled randomized clinical trial. One hundred and sixty-four patients are being recruited from December 2021. The trial includes adult patients with incurable solid tumor, CAC, loss of appetite (≥4 score on the 0 to 10 loss of appetite scale of the Edmonton Symptom Assessment System [ESAS]), Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and a predicted survival >3 months. Causes for exclusion are: highly emetogenic chemotherapy, antipsychotic or appetite stimulant administration, nausea or vomiting score >3 on the 0 to 10 scale of the ESAS, weight gain for a known cause (e.g., oedema) or central nervous system disease. Participants will be 1:1 randomized to the intervention arm (OLZ 5 mg tablet once a night for 28 days) or the control arm (placebo tablet once at night for 28 days). The primary endpoint is the change in the loss of appetite score on the 0 to 10 scale of the ESAS from day 0 to day 7 of treatment. The secondary endpoints include the change in loss of appetite score from day 0 to days 14, 21 and 28 and the change in quality of life, handgrip strength, body mass index, body weight, lean body mass, fatigue and c-reactive protein level from day 0 to day 28. NCT05243251. Cairo University.

Glucocorticosteroid and Silicone Gel During Patch Application Without Clinical Scar Improvement After Central Venous Catheter Removal: A Randomized Trial.

We studied whether glucocorticosteroid during patch occlusion has a beneficial effect on scar outcome in children and adolescents treated for cancer. A double-blinded placebo-controlled randomized clinical trial was performed. The main outcome was the Vancouver Scar Scale. Secondary outcomes were scar width and scar quality measured using the Patient and Observer Scar Assessment Scale. The patients were divided into an intervention groups and a control group. The intervention group was randomized into active and placebo group. The active treatment consisted of cream with glucocorticosteroid and fusidic acid. The placebo treatment consisted of cream with fusidic acid. Both groups received silicone gel patch after central venous catheter removal. The control group received no specific skin care. Assessment at 12 months showed that the intervention group had a significantly lower Vancouver Scar Scale and a smaller scar (0,1cm) compared with the control group ( P =0.00, P =0.02) but no benefit of glucocorticosteroid. The Patient and Observer Scar Assessment Scale showed no significant difference between the intervention and control groups ( P =0.84, P =0.36). Silicone gel sheet alone or in combination with application of glucocorticosteroid during sheet occlusion does not clinically improve scar outcome after removal of central venous catheter in children treated for neoplastic diseases.

The Effects of Vitamin K2 (Menaquinone-7) on the Leptin and Adiponectin Levels in Overweight/Obese Type 2 Diabetes Patients: A Randomized Clinical Trial

Background: Type 2 diabetes mellitus (T2DM) is a prevalent disease with metabolic consequences. Lower levels of adiponectin and higher levels of leptin were reported in T2DM. This study aimed to evaluate the effect of menaquinone-7 (MK-7) supplementation on adiponectin and leptin in overweight/obese T2DM patients. Methods: Sixty men and women with T2DM and 27 ≤ body mass index &lt; 35 kg/m2 , participated in this double-blind placebo-controlled randomized clinical trial for 12 weeks. The subjects were allocated into intervention (200 µg/day MK-7) or placebo groups. Three-day food records, anthropometrics and physical activity were assessed and fasting blood samples were collected at the pre- and post-intervention. Serum adiponectin, leptin, fasting blood sugar (FBS) and fasting insulin (FI) were measured and adiponectin to leptin ratio (A/L ratio) was calculated. Results: MK-7 decreased fasting blood sugar (P: 0.018) and fasting insulin (P: 0.012), according to a within group analysis of the 45 patients who finished the research. Fasting blood sugar (P: 0.024) and leptin levels (P: 0.032) were lower in the MK-7 group, but there were no significant changes between the groups in terms of adiponectin or the adiponectin to leptin (A/L) ratio. Conclusion: Current study showed that MK-7 supplementation could lead to significant reduction in leptin and FBS, but it has no effect on the adiponectin and A/L ratio in overweight/ obese T2DM patients.

Regulation of NLRP3 inflammasome by zinc supplementation in Behçet's disease patients: A double-blind, randomized placebo-controlled clinical trial

BackgroundOverproduction of NLRP3 inflammasome complex is one of the causes of Behcet's disease's (BD) auto-inflammatory nature. The aim of current study was to examine the effect of zinc supplementation on NLRP3 inflammasome expression; as well as clinical manifestations of BD. MethodsIn this double-blind parallel placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day elemental zinc) or placebo groups for 12 weeks. The mRNA expression of NLRP3 and caspase-1 in the leukocytes, serum level of zinc and IL-1β, anthropometric measures, and clinical manifestations of patients were collected at pre- and post-intervention phase. The Iranian Behçet's disease dynamic activity measure (IBDDAM) was scored to measure the treatment effect using the calculation of number needed to treat (NNT). Analysis of covariance was performed to obtain the corresponding effect sizes. ResultsZinc gluconate led to a significant improvement in genital ulcer (P = 0.019). Zinc supplementation decreased NLRP3 and caspase-1 genes expression compared with placebo group (baseline-adjusted P-value = 0.046 for NLRP3 and P-value = 0.003 for caspase-1), even after adjustment for the effect of confounding factors (baseline- and confounders-adjusted P-value = 0.032 for NLRP3 and P-value = 0.004 for caspase-1). Baseline and confounders adjusted effect size demonstrated that zinc was effective in reducing the serum level of IL-1β (P = 0.046). The NNT [95 %CI] for the rate of IBDDAM improvement was 3 [1.7–8.5]. ConclusionsZinc gluconate supplementation (30 mg/day) for a 3-month period can be considered as an adjuvant therapy in alleviating inflammation and genital ulcer among BD patients.

Probiotic supplement as an adjunctive therapy with Ritalin for treatment of attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled randomized clinical trial

PurposeAccumulating evidence highlights the importance of microbiota-directed intervention in neuropsychiatric disorders. This study aims to investigate the effects of probiotic supplements as an adjunct therapy in combination with Ritalin in children with attention-deficit hyperactivity disorder (ADHD).Design/methodology/approachChildren with ADHD, aged 6–12 years, who had an intelligent quotient of ≥70 were enrolled in the study. Participants were randomly assigned to either the group that received probiotics or the group that received the placebo in addition to the weight-adjusted dose of Ritalin. Parents were asked to complete the revised Conners Parent Rating Scale–short version (CPRS–RS), and the psychiatrist completed the seven-point Clinical Global Impression–Severity (CGI–S) scale. Two study groups were compared in three time points, including T1 (before intervention), T2 (at the end of fourth week) and T3 (at the end of the eighth week).FindingsA total of 38 participants completed the study. After eight weeks of intervention, the probiotic group had a significant improvement regarding CPRS–RS scores in T2 (9.4 unit, p = 0.014) and T3 (18.6 unit, p < 0.001), compared to placebo. In addition, children in the probiotic group had 0.7 unit lower CGI in T3 (p = 0.018) than the placebo group. A significant reduction of CGI scores was observed in each interval (T2 vs T1, T3 vs T2 and T3 vs T1; p < 0.05). This significant change in CGI score between intervals was also detected in the placebo group in T2 vs T1 (p = 0.002) and T3 vs T1 (p < 0.001). Mean CPRS scores of the groups were different in T2 and T3 (p = 0.011 and p < 0.001, respectively) and mean CGI scores of the two study groups were different in T3 (p = 0.018).Originality/valueEight weeks of supplementation with probiotics had a favorable effect on symptoms and severity of ADHD. Therefore, probiotics as an adjuvant treatment might have a promising efficacy regarding the management of ADHD.

The effect of menaquinone-7 supplementation on dp-ucMGP, PIVKAII, inflammatory markers, and body composition in type 2 diabetes patients: a randomized clinical trial

BackgroundType 2 diabetes mellitus (T2DM) is a common disorder that is characterized by chronic hyperglycemia and chronic inflammation, which also have a reinforcing effect on each other. The present research studied the effects of menaquinone (MK-7) supplementation on serum dp-ucMGP (dephospho uncarboxylated Matrix Gla Protein), PIVKAII (Prothrombin Induced by Vitamin K Absence), inflammatory markers and body composition indices in type 2 diabetes mellitus (T2DM) patients.MethodsThis 12-week double-blind placebo-controlled randomized clinical trial allocated 60 T2DM patients equally into a MK-7 (200 mcg/day) group or a placebo group. All patients also received dietary advice at the beginning of study and their dietary intakes were checked using a 3-day food record. The body composition of each patient was also measured and their vitamin K status was assessed using the ELISA method to measure serum dp-ucMGP and PIVKAII. In addition, inflammatory status indices were also measured, including hsCRP (high-sensitivity C-reactive protein), IL-6 (interleukin-6) and TNF-α (tumor necrosis factor alpha). All measurements were made both before and after the intervention period.ResultsIn total 45 patients completed the trial (MK-7 group = 23 and placebo group = 22). The calorie and macronutrient intake of the two groups were similar pre and post intervention. There were statistically significant increases in dietary vitamin K intake for both groups over the course of the study (p < 0.05), but the intergroup differences were not significant. The body composition indices (i.e., body fat percentage, fat mass, fat free mass, muscle mass, bone mass and total body water) were not significantly different between groups or across the trial. The serum levels of the vitamin K markers, PIVKAII and dp-ucMGP, decreased significantly in the MK-7 group over the course of the study (p < 0.05), but there was no decrease in the placebo group. However, after adjusting for the baseline levels and changes in vitamin K intake, the between group differences were only significant for PIVKAII (p < 0.05). Following the intervention, the serum levels of the inflammatory markers (hsCRP, IL-6, and TNF-α) were significantly lower in the MK-7 group (p < 0.05), but not in the placebo group. However, the between group differences in the inflammatory markers were not statistically significant.ConclusionsAlthough further studies are needed, it appears that MK-7 supplementation can be effective in improving PIVKAII levels, but not for improving dp-ucMGP, inflammatory status or the body composition indices of T2DM patients.Trial registration numberThis study was prospectively registered at the Iranian Registry of Clinical Trials on the 20th of May 2019 (ID: IRCT20100123003140N22).

Immunomodulatory and clinical responses to zinc gluconate supplementation in patients with Behçet's disease: A double-blind, randomized placebo-controlled clinical trial

Toll-like receptor (TLR) 2 and 4 are involved in the pathogenesis of Behçet's disease (BD). The current study aimed to investigate the effect of zinc supplementation on TLR-2/4 expression and the clinical manifestations of BD. In this double-blind placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30mg/day) or placebo groups for 12 weeks. Before and after the intervention, the surface and mRNA expression level of TLR-2 and TLR-4 in the leukocytes, serum level of zinc and tumor necrosis factor-α (TNF-α), quality of life, anthropometric measures, and blood pressure of patients were collected. BD activity was studied using the nonocular Iranian Behçet's disease dynamic activity measure (IBDDAM), Behçet's disease current activity form (BDCAF), and total inflammatory activity index (TIAI) at the pre-and post-intervention phases. The effect sizes were compared between two groups using analysis of covariance. There were significant decrease in TLR-2 mRNA (P=0.038) and protein expression (P=0.034) and nonocular IBDDAM score (P=0.046) in the zinc group compared to placebo at the endpoint. The serum level of zinc was increased in the zinc group (P<0.001). Zinc supplementation significantly decreased the TLR-4 surface (P=0.012) and mRNA expression (P=0.028) within the group. However, this decrease was not significant compared to the placebo group. There was no significant difference between the two groups regarding the serum level of TNF-α, BDCAF, TIAI, quality of life, anthropometric measures, and blood pressure (P>0.05). The present study revealed that zinc supplementation significantly improved nonocular IBDDAM score and TLR-2 expression in BD patients. NCT05098678.

Investigating the effect of quadruple therapy with Saccharomyces boulardii or Lactobacillus reuteri strain (DSMZ 17648) supplements on eradication of Helicobacter pylori and treatments adverse effects: a double-blind placebo-controlled randomized clinical trial

BackgroundThe goal of this study was to investigate the effects of treatment with Saccharomyces boulardii and Lactobacillus reuteri on the eradication of Helicobacter pylori and Adverse effects (AEs) of the treatment.ResultsThis study was a double-blind, randomized, placebo-controlled trial. And, eradication of H. pylori was reported comparing quadruple therapy include of PPI (proton pomp inhibitor), bismuth subcitrate, clarithromycin, and amoxicillin versus quadruple therapy supplemented with S. boulardii and L. reuteri DSMZ 17648. For this aim, a total of 156 patients were included in the current study; and patients positive for H. pylori infection (n = 156) were randomly assigned to 3 groups: 52 patients (Group P) received conventional quadruple therapy plus L. reuteri, 52 patients (Group S) received conventional quadruple therapy plus S. boulardii daily, for 2 weeks, and 52 patients were in the control group (Group C). At the end of the treatment period, all the subjects continued to take proton pump inhibitor (PPI) alone for 14 days, and then, no medication was given for 2 weeks again. During follow-up, gastrointestinal symptoms were assessed using an evaluation scale (Glasgow dyspepsia questionnaire [GDQ]), and AEs were assessed at 7, 14, 21, and 28 days. As a result, all patients completed the treatment protocol in all groups by the end of the study. Additionally, eradication therapy was effective for 94.2% of subjects in Group S, 92.3% of subjects in Group P, and 86.5% of subjects in the control group, with no differences between treatment arms. In Group S, the chance of developing symptoms of nausea (OR = 2.74), diarrhea (OR = 3.01), headache (OR = 10.51), abdominal pain (OR = 3.21), and anxiety (OR = 3.58) was significantly lower than in the control group (p < 0.05).ConclusionS. boulardii could significantly reduce some AEs of H. pylori eradication therapy, but effectiveness of Lactobacillus reuteri on these cases was not significant. It is recommended to conduct the future research with larger sample size in order to investigate the effect.Trial registration: IRCT20200106046021N1, this trial was registered on Jan 14, 2020.

Fecal microbiota transplantation to improve efficacy of immune checkpoint inhibitors in renal cell carcinoma (TACITO trial).

TPS407 Background: Renal cell carcinoma (RCC) is the 6° most common cancer in men and the 8° in women in the USA. In Italy RCC incidence was 11,500 new cases in 2017, while mortality was 3,371 cases in 2015. Increasing evidence suggests that response to immune checkpoint inhibitors (ICIs), a novel treatment for advanced RCC (aRCC) and other epithelial tumors, can be influenced by the patient gut microbiota. Fecal microbiota transplantation (FMT) is a novel treatment option aimed to restore healthy gut microbiota, and is the most effective therapy for recurrent C. difficile infection. Preliminary nonrandomized findings show that FMT is able to improve efficacy of ICIs in patients with advanced melanoma. The aim of this study is to evaluate, through a double-blinded placebo-controlled randomized clinical trial, the efficacy of targeted FMT (from donors who are responding to ICIs) in improving response rates to ICIs in subjects with aRCC. Methods: 50 patients who are about to receive, or have started by &lt;8 weeks, pembrolizumab + axitinib as first-line therapy for aRCC will be enrolled. Exclusion criteria include major comorbidities, concomitant GI or autoimmune disorders, or HIV, HBV, HCV infection, continuative corticosteroid therapy, previous treatment with systemic immune-suppressants or immune-modulatory drugs, antibiotic therapy within 4 weeks prior to enrollment. Stool samples and clinical data will be collected at baseline. Then, patients will be randomized to donor FMT or placebo FMT. They will receive the first infusion by colonoscopy and then oral frozen fecal or placebo capsules (8 capsules t.i.d.) 90 and 180 days after the first FMT. Stool donors will be searched among long-term (&gt;12 months) responders to ICIs, and will be selected by following protocols recommended by international guidelines. Patients in the FMT group will always receive feces from the same donor throughout the three fecal transplants. Frozen fecal batches and frozen fecal capsules will be manufactured according to international guidelines. Patients will be followed-up 7, 15, 30, 90, 180, 270, and 360 days after randomization for clinical evaluation and collection of stool samples. Patients will also undergo radiological assessment at 90, 180, 270 and 360 days after randomization. Microbiome analysis will be performed with shotgun metagenomics. The primary endpoint is the progression-free survival (PFS) at 12 months. Secondary endpoints are: objective response rate at 12 months; overall survival at 12 months; adverse events after FMT; microbiome changes after FMT. Sample size calculation was based on the hypothesis that FMT can improve the 1-year PFS rate from 60% (reported 1-year PFS for SOC) to 80% wen associated to SOC. Clinical trial information: NCT04758507.

Double-blind placebo-controlled randomized clinical trial to assess the efficacy of montelukast in mild to moderate respiratory symptoms of patients with long COVID: E-SPERANZA COVID Project study protocol

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic continues to affect the globe. After 18 months of the SARS-CoV-2 emergence, clinicians have clearly defined a subgroup of patients with lasting, disabling symptoms. While big strides have been made in understanding the acute phase of SARS-CoV-2 infection, the pathophysiology of long COVID is still largely unknown, and evidence-based, effective treatments for this condition remain unavailable.ObjectivesTo evaluate the efficacy of 10 mg oral montelukast every 24 h versus placebo in improving quality of life associated with mild to moderate respiratory symptoms in patients with long COVID as measured with the COPD Assessment Test (CAT) questionnaire. The secondary objectives will evaluate the effect of montelukast versus placebo on improving exercise capacity, COVID-19 symptoms (asthenia, headache, mental confusion or brain fog, ageusia, and anosmia), oxygen desaturation during exertion, functional status, and mortality.Methods and analysisPhase III, randomized, double-blind clinical trial. We will include 18- to 80-year-old patients with SARS-CoV-2 infection and mild to moderate respiratory symptoms lasting more than 4 weeks. Participants will be randomly allocated in a 1:1 ratio to the intervention (experimental treatment with 10 mg/day montelukast) or the control group (placebo group), during a 28-day treatment. Follow-up will finish 56 days after the start of treatment. The primary outcome will be health-related quality of life associated with respiratory symptoms according to the COPD Assessment Test 4 weeks after starting the treatment. The following are the secondary outcomes: (a) exercise capacity and oxygen saturation (1-min sit-to-stand test); (b) Post-COVID-19 Functional Status Scale; (c) other symptoms: asthenia, headache, mental confusion (brain fog), ageusia, and anosmia (Likert scale); (d) use of healthcare resources; (e) mortality; (f) sick leave duration in days; and (g) side effects of montelukast.Ethics and disseminationThis study has been approved by the Clinical Research Ethics Committee of the IDIAPJGol (reference number 21/091-C). The trial results will be published in open access, peer-reviewed journals and explained in webinars to increase awareness and understanding about long COVID among primary health professionals.Trial registrationClinicalTrials.govNCT04695704. Registered on January 5, 2021. EudraCT number 2021-000605-24. Prospectively registered.

Efficacy and safety of acetylcysteine for the prevention of liver injury in COVID-19 intensive care unit patients under treatment with remdesivir.

Aim:The present double-blinded placebo-controlled randomized clinical trial evaluated prophylactic use of acetylcysteine for the prevention of liver injury in patients with severe COVID-19 pneumonia under treatment with remdesivir.Background:Liver injury is reportedly common in patients with severe COVID-19 pneumonia and can occur not only as a result of disease progression, but as an iatrogenic reaction to remdesivir.Methods:A total of 83 adult patients with severe COVID-19 pneumonia were randomly assigned in parallel groups to receive either acetylcysteine or placebo. All the patients received standard care according to institutional protocols, including remdesivir for a total of five days. One gram acetylcysteine was administered intravenously every 12 hours for 42 patients, and 41 patients received the same volume of 0.9% sodium chloride as placebo (Trial Registration: www.irct.ir identifier, IRCT20210726051995N1). Results:After 5 days, median aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in the acetylcysteine than in the placebo group. Of those who received the placebo, 30 (73.2%), 4 (9.7%), and 3 (7.3%) patients had serum AST levels elevated between 1-2.5, 2.5-5, and over 5 times the upper limit of normal (ULN), respectively; while in the acetylcysteine group, 33 (78.6%) and 0 patients had AST levels between 1-2.5 and over 2.5 times ULN, respectively (p-value=0.037). In the acetylcysteine group, 23 (54.8%), 1 (2.4%), and 1 (2.4%) patient had serum ALT levels elevated between 1-2.5, 2.5-5, and over 5 times ULN, respectively; in the placebo group, however, 24 (58.5%), 7 (17.1%), and 1 (2.4%) patient had serum ALT levels between 1-2.5, 2.5-5, and over 5 times ULN, respectively (p-value=0.073). Conclusion:Intravenous administration of acetylcysteine significantly prevents liver transaminases elevation and liver injury in seriously ill COVID-19 patients treated with remdesivir.

Effect of 0.5% povidone-iodine on the nasopharyngeal and oropharyngeal viral loads in patients with COVID-19: A double-blind placebo-controlled randomized clinical trial.

The povidone-iodine (PvP-I) nasal antiseptic has been shown to completely inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro at variable concentrations. This study was performed to investigate the effect of 0.5% PvP-I nasal drops and oral gargles on the nasopharyngeal and oropharyngeal viral loads in SARS-CoV-2-positive patients. This was a double-blind, placebo-controlled, randomized clinical trial among patients aged ≥18 years with reverse-transcriptase polymerase chain reaction confirmed in the mild to moderate category of SARS-CoV-2 infection. A total of 32 patients were randomly assigned to receive either freshly prepared 0.5% PvP-I solution or distilled water in the form of supervised self-administered 4-5 nasal drops, followed by 20 ml for gargling for at least 30 seconds. The main outcome measure was the mean change in viral titer and Ct values in the nasopharyngeal and oropharyngeal samples at baseline, 5 minutes, and 3 hours post intervention. The mean change in viral titers across the time duration for the test group when compared with the control group was not statistically significant (P = 0.109). However, the mean change in Ct value was found to be borderline statistically significant (P = 0.042). Noticeable differences were noted among the mean viral titers and Ct values in the intervention group when plotted against the time of testing as compared to the control group. PvP-I solution at 0.5% dilution was well tolerated, and no evident side effects were reported. This study shows that 0.5% PvP-I has an effect on reducing nasopharyngeal and oropharyngeal viral loads in COVID-19 patients. This can be of substantial aid for the primary care physicians, especially for the practitioners in remote and resource poor areas.

Probiotic milk drink as adjuvant therapy for the treatment of periodontitis: a randomized clinical trial with 180 days follow-up

The effect of probiotic milk drinks associated with non-surgical periodontal therapy (NSPT) in treating periodontitis was evaluated. A double-blind placebo-controlled randomized clinical trial with patients with periodontitis was conducted. Two groups were used: TG (n=15, test group, probiotic milk drink, Lacticaseibacillus casei 01, 8-9 log CFU/mL) and CG (n=15, control group, conventional milk drink). The milk drinks (100 mL) were consumed once a day at breakfast for 15 days. Both groups also received NSPT, supra and subgingival scaling and root planning per quadrant, and oral hygiene instruction. All patients were clinically evaluated after 30, 90, and 180 days of the last NSPT session. Reductions in clinical attachment loss and probing pocket depth were observed at 30 days in both groups, maintained throughout the follow-up. Decreases in visible plaque index (VPI) and bleeding on probing were observed after probiotic milk drink consumption for 30 days, suggesting an effect provided by probiotics in the control of biofilm and inflammation. However, the impact on VPI was not persistent for more than 30 days, demonstrating the need for regular consumption of the probiotic milk drink. In conclusion, probiotic milk drinks may be used as adjuvant therapy to treat periodontitis.

Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study.

(1) Background: Based on its antiviral activity, anti-inflammatory properties, and functional inhibition effects on the acid sphingomyelinase/ceramide system (FIASMA), we sought to examine the potential usefulness of the H1 antihistamine hydroxyzine in patients hospitalized for COVID-19. (2) Methods: In a multicenter observational study, we included 15,103 adults hospitalized for COVID-19, of which 164 (1.1%) received hydroxyzine within the first 48 h of hospitalization, administered orally at a median daily dose of 25.0 mg (SD = 29.5). We compared mortality rates between patients who received hydroxyzine at hospital admission and those who did not, using a multivariable logistic regression model adjusting for patients’ characteristics, medical conditions, and use of other medications. (3) Results: This analysis showed a significant association between hydroxyzine use and reduced mortality (AOR, 0.51; 95%CI, 0.29–0.88, p = 0.016). This association was similar in multiple sensitivity analyses. (4) Conclusions: In this retrospective observational multicenter study, the use of the FIASMA hydroxyzine was associated with reduced mortality in patients hospitalized for COVID-19. Double-blind placebo-controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results, as are studies to examine the potential usefulness of this medication for outpatients and as post-exposure prophylaxis for individuals at high risk for severe COVID-19.

Effects of sodium selenite and selenium-enriched yeast on cardiometabolic indices of patients with atherosclerosis: A double-blind randomized clinical trial study.

Introduction: Atherosclerosis and related cardiovascular diseases (CVDs) are the major causes of mortality worldwide. The available reports regarding the effects of selenium (Se) supplementation in the realm of atherosclerosis have been equivocal. The present investigation is aimed to assess the effects of sodium selenite and Se-enriched yeast supplementation on metabolic parameters among atherosclerotic patients. Methods: In this double-blind placebo-controlled randomized clinical trial, 60 patients diagnosed with atherosclerosis were randomly allocated into either 200 μg/day selenite, yeast, or placebo groups for eight consecutive weeks. Serum levels of lipid profile and glycemic indices were measured at the baseline and end of the intervention. Results: There were no significant within-or between-group changes in levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), fasting blood sugar, insulin, and homeostatic model assessment for IR throughout the study (P ≥0.05). Only the low density lipoprotein cholesterol (LDL-c) levels were significantly lower in the yeast group in comparison with the placebo group (P = 0.015). Conclusion: The administration of Se-enriched yeast is significantly effective in decreasing LDL-c levels in patients with atherosclerosis. Additional clinical trial studies investigating the effect of Se administration on glucose homeostasis parameters and lipid profiles in atherosclerotic patients are suggested for a more definitive conclusion.

Lithium and preventing chemotherapy-induced peripheral neuropathy in breast cancer patients: a placebo-controlled randomized clinical trial

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of some chemotherapy regimens. Lithium has been suggested for CIPN in some animal studies. We aimed to study lithium’s preventive effect on CIPN in breast cancer patients treated with taxanes and platinum-based medications.MethodA double-blind placebo-controlled randomized clinical trial (RCT) was implemented on 36 breast cancer patients in two equal-size groups by block randomization. Participants in both groups consumed daily tablets, either placebo or lithium (300 mg), for 5 days in each course of chemotherapy. The tablets were prescribed 1 day before the start of chemotherapy. The electromyography (EMG) and nerve-conduction-velocity (NCV) tests were achieved before the first chemotherapy, 3 and 9 months after the treatment. The changes and signs or symptoms of CIPN, such as numbness, tingling, freezing, sensitivity to touch, muscle weakness, fibrillation, and knee and elbow reflex disorders, were recorded by examination. The trend of outcome changes was compared between two groups during the 9 months of study.ResultsIn both groups, neurologic signs and symptoms were exacerbated during the first 3 months and improved up to the ninth month of study. Results showed significant changes of all EMG-NCV variables during the 9 months of research in each group (P < 0.001), but the interaction of time and group effect was not significant in none of those indices. All symptoms changed significantly over the study time (P < 0.001) without significant statistical difference between the two groups (P=0.352). No side effect was found during the study.ConclusionThe study showed that 300 mg lithium prescription once daily for 5 days might not effectively prevent CIPN in breast cancer patients. Evaluation of lithium effect on CIPN on different cancers in future studies is suggested.Trial registrationIranian Registry of Clinical Trials IRCT20160813029327N10. Registration date: May 16, 2018.