Double-blind Placebo-controlled Randomized Clinical Trial Research Articles

Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease at High Risk of Exacerbation: The BICS Randomized Clinical Trial.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that β-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission. To test whether bisoprolol decreased COPD exacerbations in people with COPD at high risk of exacerbations. The Bisoprolol in COPD Study (BICS) was a double-blind placebo-controlled randomized clinical trial conducted in 76 UK sites (45 primary care clinics and 31 secondary clinics). Patients with COPD who had at least moderate airflow obstruction on spirometry (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity <0.7; FEV1 <80% predicted) and at least 2 COPD exacerbations treated with oral corticosteroids, antibiotics, or both in the prior 12 months were enrolled from October 17, 2018, to May 31, 2022. Follow-up concluded on April 18, 2023. Patients were randomly assigned to bisoprolol (n = 261) or placebo (n = 258). Bisoprolol was started at 1.25 mg orally daily and was titrated as tolerated during 4 sessions to a maximum dose of 5 mg/d, using a standardized protocol. The primary clinical outcome was the number of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both during the 1-year treatment period. Safety outcomes included serious adverse events and adverse reactions. Although the trial planned to enroll 1574 patients, recruitment was suspended from March 16, 2020, to July 31, 2021, due to the COVID-19 pandemic. Two patients in each group were excluded postrandomization. Among the 515 patients (mean [SD] age, 68 [7.9] years; 274 men [53%]; mean FEV1, 50.1%), primary outcome data were available for 514 patients (99.8%) and 371 (72.0%) continued taking the study drug. The primary outcome of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both was 526 in the bisoprolol group, with a mean exacerbation rate of 2.03/y, vs 513 exacerbations in the placebo group, with a mean exacerbation rate of 2.01/y. The adjusted incidence rate ratio was 0.97 (95% CI, 0.84-1.13; P = .72). Serious adverse events occurred in 37 of 255 patients in the bisoprolol group (14.5%) vs 36 of 251 in the placebo group (14.3%; relative risk, 1.01; 95% CI, 0.62-1.66; P = .96). Among people with COPD at high risk of exacerbation, treatment with bisoprolol did not reduce the number of self-reported COPD exacerbations requiring treatment with oral corticosteroids, antibiotics, or both. isrctn.org Identifier: ISRCTN10497306.

Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes

The prevalence of e-cigarette use among US adults, especially young adults, is rising. Many would like to quit vaping nicotine but are unable to do so. Cytisinicline, a plant-based alkaloid, targets nicotinic acetylcholine receptors, reduces nicotine dependence, and helps adults to stop smoking cigarettes. Cytisinicline may also help e-cigarette users to quit vaping. To determine the efficacy and safety of cytisinicline vs placebo to produce abstinence from e-cigarette use in adults seeking to quit vaping nicotine. This double-blind placebo-controlled randomized clinical trial compared 12 weeks of treatment with cytisinicline vs placebo, with follow-up to 16 weeks. It was conducted from July 2022 to February 2023 across 5 US clinical trial sites. A total of 160 adults who vaped nicotine daily, sought to quit, and did not currently smoke cigarettes were enrolled, and 131 (81.9%) completed the trial. Participants were randomized (2:1) to cytisinicline, 3 mg, taken 3 times daily (n = 107) or placebo (n = 53) for 12 weeks. All participants received weekly behavioral support. Biochemically verified continuous e-cigarette abstinence during the last 4 weeks of treatment (weeks 9-12; primary outcome) and through 4 weeks posttreatment (weeks 9-16; secondary outcome). Missing outcomes were counted as nonabstinence. Of 160 randomized participants (mean [SD] age, 33.6 [11.1] years; 83 [51.9%] female), 115 (71.9%) formerly smoked (≥100 lifetime cigarettes). Continuous e-cigarette abstinence in cytisinicline and placebo groups occurred in 34 of 107 participants (31.8%) vs 8 of 53 participants (15.1%) (odds ratio, 2.64; 95% CI, 1.06-7.10; P = .04) at end of treatment (weeks 9-12) and in 25 of 107 participants (23.4%) vs 7 of 53 participants (13.2%) during weeks 9 to 16 (odds ratio, 2.00; 95% CI, 0.82-5.32; P = .15). There was no evidence, based on nonsignificant interactions, that cytisinicline efficacy differed in subgroups defined by demographic characteristics, vaping pattern, e-cigarette dependence, or smoking history. Cytisinicline was well tolerated, with 4 participants (3.8%) discontinuing cytisinicline due to an adverse event. In this randomized clinical trial, cytisinicline for 12 weeks, with behavioral support, demonstrated efficacy for cessation of e-cigarette use at end of treatment and was well tolerated by adults, offering a potential pharmacotherapy option for treating nicotine e-cigarette use in adults who seek to quit vaping. These results need confirmation in a larger trial with longer follow-up. ClinicalTrials.gov Identifier: NCT05431387.

Coenzyme Q10 supplementation in burn patients: a double-blind placebo-controlled randomized clinical trial

BackgroundBurn injuries are important medical problems that, aside from skin damage, cause a systemic response including inflammation, oxidative stress, endocrine disorders, immune response, and hypermetabolic and catabolic responses which affect all the organs in the body. The aim of this study was to determine the effect of coenzyme Q10 (CoQ10) supplementation on inflammation, oxidative stress, and clinical outcomes in burn patients.MethodsIn a double-blind placebo-controlled randomized clinical trial, 60 burn patients were randomly assigned to receive 100 mg CoQ10 three times a day (total 300 mg/day) or a placebo for 10 days. Inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), oxidative stress markers including total antioxidant capacity (TAC), malondialdehyde (MDA) and superoxide dismutase (SOD) activity, fasting blood glucose (FBG), blood urea nitrogen (BUN), creatinine, white blood cells (WBC), and body temperature were assessed as primary outcomes and albumin, prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), other hematological parameters, blood pressure, O2 saturation, ICU duration, and 28-mortality rate were assessed as secondary outcomes.ResultsFifty-two participants completed the trial. CRP and ESR levels were not significantly different between CoQ10 and placebo groups at the end of the study (P = 0.550 and P = 0.306, respectively). No significant differences between groups were observed for TAC (P = 0.865), MDA (P = 0.692), and SOD activity (P = 0.633) as well. Administration of CoQ10 resulted in a significant increase in albumin levels compared to placebo (P = 0.031). There was no statistically significant difference between the two groups in other measured outcomes (P > 0.05).ConclusionResults showed that in patients with burn injury, CoQ10 administration had no effect on inflammatory markers and oxidative stress, although serum albumin levels were improved after supplementation. Further studies with albumin as the primary outcome are needed to confirm this finding.

Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infants

Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Healthy 5-7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.govNCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000g and gestational age ≥32 weeks.Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4-5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3-1.9) after routine MMR.Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9-1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8-4.0); none deemed vaccine related. Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5-7 months was safe and not associated with higher rates of reactogenicity than placebo. Innovation Fund Denmark.

Adaptive Smoking Cessation Using Precessation Varenicline or Nicotine Patch

Adaptive pharmacotherapy, ie, starting a medication regimen and then modifying that regimen based on patient response, is common in many medical domains but is not common in smoking cessation. Recently, studies have found that adaptive treatment using precessation nicotine patches is efficacious for smoking cessation; however, adaptive treatment using precessation varenicline and adaptive treatment in clinical practice settings have not been fully assessed. To determine whether adaptive pharmacotherapy leads to higher smoking abstinence rates than standard pharmacotherapy in a clinical practice setting. This double-blinded stratified placebo-controlled randomized clinical trial compared adaptive treatment with standard treatment for smoking cessation. The study was conducted at a university health system in Durham, North Carolina, from February 2018 to May 2020 and was stopped early due to COVID-19. Data were analyzed as intent-to-treat from May 24, 2021, to February 27, 2022. Participants were allowed to choose varenicline or nicotine patches and were then randomized to adaptive or nonadaptive (standard) treatment. Participants started on their chosen medication (adaptive) or placebo (standard) 4 weeks before their target quit day. Two weeks later, participants were assessed for treatment response. Adaptive participants who did not decrease daily cigarettes smoked by at least 50% (nonresponders) received bupropion in addition to their chosen medication. Participants in the adaptative treatment group who did decrease daily cigarettes smoked by at least 50% (responders) and participants in the standard treatment group received additional placebo bupropion. Participants in the standard treatment group received varenicline starting 1 week before the target quit date or nicotine patches starting on the target quit day. All participants received brief behavioral support. The main outcome was biochemically verified 30-day continuous smoking abstinence 12 weeks after their target quit smoking day. Other measures included demographic characteristics, smoking history, and repeated smoking assessments. Of the planned 300 participants, a total of 188 participants (mean [SD] age, 49.1 [12.5] years; 102 [54%] female) were enrolled before the trial was stopped because of the COVID-19 pandemic. A total of 127 participants chose to use varenicline, including 64 randomized to adaptive treatment and 63 randomized to standard treatment, and 61 participants chose to use nicotine patches, including 31 randomized to adaptive treatment and 30 randomized to standard treatment. At baseline, participants smoked a mean (SD) of 15.4 (7.3) cigarettes per day. At 12 weeks after the target quit day, biochemically verified 30-day continuous smoking abstinence was observed in 23 of 95 participants (24%) in the adaptive treatment group and 8 of 93 participants (9%) in the standard treatment (odds ratio [OR], 3.38; 95% CI, 1.43-7.99; P = .004); among participants who used varenicline, 30-day continuous abstinence was 18 participants (28%) in the adaptive treatment group, and 5 participants (8%) in the standard treatment group (OR, 4.54; 95% CI, 1.57-13.15); among participants who used nicotine patches, 30-day continuous abstinence was 5 participants (16%) in the adaptive treatment group and 3 participants (10%) in the standard treatment group (OR, 1.73; 95% CI, 0.38-7.99). Sleep problems were more common for participants in the varenicline adaptive treatment group than in the varenicline standard treatment group (rate ratio, 1.74; 95% CI, 1.18-2.58; P = .03). This randomized clinical trial found that adaptive pharmacotherapy was efficacious for smoking cessation treatment in a practice setting. ClinicalTrials.gov Identifier: NCT02501265.

Minocycline for sporadic and hereditary cerebral amyloid angiopathy (BATMAN): study protocol for a placebo-controlled randomized double-blind trial

BackgroundCerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the elderly. The presence of the amyloid-beta protein in the vessel wall may induce a chronic state of cerebral inflammation by activating astrocytes, microglia, and pro-inflammatory substances. Minocycline, an antibiotic of the tetracycline family, is known to modulate inflammation, gelatinase activity, and angiogenesis. These processes are suggested to be key mechanisms in CAA pathology. Our aim is to show the target engagement of minocycline and investigate in a double-blind placebo-controlled randomized clinical trial whether treatment with minocycline for 3 months can decrease markers of neuroinflammation and of the gelatinase pathway in cerebrospinal fluid (CSF) in CAA patients.MethodsThe BATMAN study population consists of 60 persons: 30 persons with hereditary Dutch type CAA (D-CAA) and 30 persons with sporadic CAA. They will be randomized for either placebo or minocycline (15 sporadic CAA/15 D-CAA minocycline, 15 sporadic CAA/15 D-CAA placebo). At t = 0 and t = 3 months, we will collect CSF and blood samples, perform a 7-T MRI, and collect demographic characteristics.DiscussionThe results of this proof-of-principle study will be used to assess the potential of target engagement of minocycline for CAA. Therefore, our primary outcome measures are markers of neuroinflammation (IL-6, MCP-1, and IBA-1) and of the gelatinase pathway (MMP2/9 and VEGF) in CSF. Secondly, we will look at the progression of hemorrhagic markers on 7-T MRI before and after treatment and investigate serum biomarkers.Trial registrationClinicalTrials.gov NCT05680389. Registered on January 11, 2023

P-47 Double-blind placebo-controlled randomized clinical trial on the concurrent use of crocin during chemoradiation of esophageal squamous cell carcinoma

P-47 Double-blind placebo-controlled randomized clinical trial on the concurrent use of crocin during chemoradiation of esophageal squamous cell carcinoma

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.

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1β, and IL-18-were assessed at enrollment and after 48-72h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5mg tid for 5days, followed by 0.5mg bid for another 5days. Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1β. Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. RBR-8jyhxh.

Preventive CGRP-targeted therapies for chronic migraine with and without medication-overuse headache

Background: Calcitonin gene-related peptide (CGRP) targeted therapies are an important breakthrough in migraine prevention. Randomized clinical trials, post-hoc analyses, and phase IV studies have demonstrated their efficacy and safety in chronic migraine patients, including those with concomitant medication-overuse and medication-overuse headache. Real world evidence studies support these findings and provide realistic endpoints for estimation of effect. Methods and results We have performed a narrative review including results from double-blind placebo-controlled randomized clinical trials and real-world evidence studies regarding efficacy of the CGRP(-receptor) monoclonal antibodies and CGRP-receptor antagonists (gepants) in patients with chronic migraine with concomitant medication overuse (headache). We have included patient profiles and main efficacy endpoints (monthly migraine days, monthly headache days, monthly acute medication days and percentage responder rates). Conclusion The results of this review show that CGRP monoclonal antibodies are effective in chronic migraine patients, also in those with medication overuse (headache). At the time of this review, atogepant clinical trials in chronic migraine have not been communicated. Direct comparative studies are needed for comparison with other treatment options.

Myo-inositol supplementation improves cardiometabolic factors, anthropometric measures, and liver function in obese patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of metabolic syndrome is closely associated with type 2 diabetes mellitus. Myo-inositol (MI)-a 6-C sugar alcohol-with insulin-mimetic, anti-diabetic, lipid-lowering, and anti-inflammatory properties has exerted favorable effects on insulin resistance-related disorders and metabolic disease, while recent animal studies revealed its positive effects on liver function. This study aimed to investigate the effects of MI supplementation on cardiometabolic factors, anthropometric measures, and liver function in obese patients with NAFLD. This double-blinded placebo-controlled randomized clinical trial was carried out on 48 obese patients with NAFLD who were randomly assigned to either MI (4g/day) or placebo (maltodextrin 4g/day) along with dietary recommendations for 8 weeks. Glycemic indices, lipid profile, liver enzymes anthropometric measures, and blood pressure were evaluated pre- and post-intervention. Dietary intakes were assessed using a 3-day 24 h recall and analyzed by Nutritionist IV software. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), and beta-cell function (HOMA-B) was also estimated. Anthropometric measures decreased significantly in both groups, while the reduction in weight (p = 0.049) and systolic blood pressure (p = 0.006) in the MI group was significantly greater than in the placebo group after adjusting for baseline values and energy intake. Although energy and macronutrient intakes decreased significantly in both groups, between-group differences were not significant after adjusting for the potential confounders. MI supplementation led to a significant reduction in serum fasting insulin (p = 0.008) and HOMA-IR (p = 0.046). There were significant improvements in lipid profile, liver enzymes, and aspartate aminotransferase/alanine aminotransferase ratio as well as serum ferritin level in the MI group, compared to the placebo group at the endpoint. By MI supplementation for eight weeks, 1 in 3 patients reduced one- grade in the severity of NAFLD. MI supplementation could significantly improve IR, lipid profile, and liver function in patients with NAFLD. Further clinical trials with larger sample sizes, longer duration, different MI doses, and other inositol derivatives are recommended.

Vitamin D supplementation on prediabetic adults with vitamin D deficiency: a double-blind placebo-controlled randomized clinical trial

Hypovitaminosis D (&lt;20 ng/mL) is thought to increase insulin resistance and meta-inflammation contributing to the pathogenesis of diabetes mellitus (DM). Correcting vitamin D deficiency in people with prediabetes might halt its progression to DM. The aim of this study was to examine the effect of vitamin D supplementation on insulin resistance, glycemic status, and inflammation in prediabetic adults with vitamin D deficiency. This doubleblind randomized placebo-controlled trial was done among 27 newly detected prediabetic adults with hypovitaminosis D randomly assigned to 60,000 IU of vitamin D weekly for eight weeks followed by monthly for the next four months or placebo along with lifestyle modification in both groups [vitamin D (n= 14) vs. Placebo (n=13). They were comparable in terms of sex, age and borlymass index. Glycemic status, fasting plasma glucose (FPG) and Hemoglobin A1C (HbA1C), insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) and inflammatory marker high sensitivity C reactive protein (hs-CRP) were measured at baseline and after six months of intervention. Vitamin D levels (ng/mL) increased in both groups from baseline (vitamin D vs. placebo: 12.2±5.9 vs. 3.9±3.5, mean±SD). FPG (mmol/L) significantly decreased in the Vitamin D group (before vs. after: 5.9±0.6 vs. 5.5±0.7, P=0.016, mean±SD), whereas HbA1C (%) and hs- CRP (mg/L) significantly increased in the placebo group (before vs. after- HbA1C: 5.8±0.3 vs. 6.0±0.4, P&lt;0.001; hs-CRP: 5.0±4.4 vs. 5.6±4.9, P=0.039, mean±SD). Percent changes in glycemic status, HOMA-IR, and hs-CRP were statistically similar between the groups. Our study failed to demonstrate the positive effects of vitamin D supplementation on reducing glucose, insulin resistance, or inflammatory marker in prediabetic adult patients with hypovitaminosis D. BSMMU J 2022; 15(3): 167-174

Effect of vitamin A on recovery from the acute phase of multiple sclerosis-related optic neuritis, double-blind, randomized, placebo-controlled trial.

Optic neuritis (ON) is one of the main neuro-ophthalmic presentations of multiple sclerosis (MS), and it causes optic nerve atrophy and axonal loss. However, so far, there is no effective treatment to improve long-term outcomes. In a double-blind placebo-controlled randomized clinical trial, 50 patients with MS-related ON were allocated into two arms (24 in the control group and 26 in the intervention group) receiving either 25000IU retinyl palmitate or an identical placebo for six months. Visual evoked potential (VEP), visual acuity, and the retinal nerve fiber layer (RNFL) thickness were evaluated and compared before and after the treatment. RNFL thickness reduction in the affected eyes at sixth month compared to the baseline were 14.81 and 19.46 μm, in the intervention and control groups, respectively (P=0.017). However, VitA therapy did not affect visual acuity and VEP. Vitamin A supplementation in the patients with acute ON in MS could lessen optic nerve axonal loss.

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.