Placebo-controlled Clinical Trial Research Articles

Anamorelin for the Treatment of Cancer Anorexia-Cachexia Syndrome.

The following review will highlight the development of anamorelin to treat cancer anorexia-cachexia syndrome (CACS) including the potential benefits, limitations, and future directions. Ghrelin, a 28-amino acid peptide hormone, is secreted by the stomach mucosa and regulates appetite, promotes lipogenesis, increases body weight, improves gastric motility, reduces catabolic wasting and inflammation. Several randomized, double-blind, placebo-controlled clinical trials evaluating anamorelin, a ghrelin agonist, for the treatment of CACS have reported improvement in appetite and body composition including both lean body and fat mass; however, most studies noted no improvement in physical function as assessed by measuring non-dominant hand-grip strength. Common adverse effects of anamorelin include the development of diabetes mellitus, hyperglycemia, and less frequently, hepatic abnormalities and cardiovascular events including conduction abnormalities, hypertension, and ischemic cardiomyopathy. Anamorelin has the potential to stimulate appetite, improve gastric movement, and may have anti-inflammatory effects on patients with CACS. In patients with cancer, studies involving anamorelin combined with other multimodal treatments including nutrition counseling (branched chain amino acids, omega 3 fatty acids, and other nutrients), exercise, treatment of hormonal abnormalities including hypogonadism and hypovitaminosis D, and anti-inflammatory agents are needed. Compliance with multimodality treatment has been a barrier and future studies may need to incorporate motivational counseling to promote adherence.

Dexmedetomidine use during orthotopic liver transplantation surgery on early allograft dysfunction: A randomized controlled trial.

Previous studies have shown a protective effect of dexmedetomidine use in kidney transplantation. In contrast, it is not known whether intraoperative administration of dexmedetomidine can reduce early allograft dysfunction incidence following liver transplantation. To investigate the effect of dexmedetomidine use during surgery on early allograft dysfunction following orthotopic liver transplantation (OLT). This is a single-center, double-blinded, placebo-controlled randomized clinical trial. 330 adult patients undergoing orthotopic liver transplantation were enrolled from Jan 14th, 2019 to May 22nd, 2022. Patients received dexmedetomidine or normal saline during surgery. 1 year follow-ups were recorded. Patients were randomized to two groups receiving either dexmedetomidine or normal saline intraoperatively. For patients in the dexmedetomidine group, a loading dose (1μg/kg over 10 min) of dexmedetomidine was given after induction of anesthesia followed by a continuous infusion (0.5μg/kg /h) until the end of surgery. For patients in the normal saline group, an equal volume loading dose of 0.9% saline was given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. The primary outcome was early allograft dysfunction. Secondary outcomes included primary graft non-function, acute kidney injury and acute lung injury/ acute respiratory distress syndrome. Of 330 patients included in the intention-to-treat analysis, 165 were in the dexmedetomidine group (mean [SD] age, 49 [10] years; 117 [70.9%] men), and 165 were in the normal saline group (mean SD age, 49 [9] years; 118 [74%] men). 39 (24.4%) patients in the dexmedetomidine group and 31 (19.4%) in normal saline group developed early allograft dysfunction and the difference was statistically insignificant (P=0.28). Secondary outcomes including primary graft non-function and acute kidney injury was similar between the two groups. Intraoperative administration of dexmedetomidine did not reduce early allograft dysfunction rate after orthotopic liver transplantation.

Safety and Efficacy of AlphaWave® L-Theanine Supplementation for 28Days in Healthy Adults with Moderate Stress: A Randomized, Double-Blind, Placebo-Controlled Trial.

Prolonged periods of stress may lead to negative health consequences. AlphaWave® L-Theanine was safe and efficacious during an acute stress challenge. However, double-blind, placebo-controlled clinical trials investigating the longer term effects of L-theanine supplementation on stress are warranted. Thirty healthy adults (18-65years) with moderate stress were randomized to AlphaWave® L-Theanine (400mg L-theanine/day) or placebo (n = 15/group) for 28days. Stress was assessed by salivary cortisol, Perceived Stress Scale (PSS) and Depression, Anxiety and Stress Scale-21; sleep was assessed by the Healthy People Sleep Quality Index and actigraphy device; cognition was assessed by Computerized Mental Performance Assessment System; mood was assessed by Profile of Mood States. All outcomes were measured at baseline, Days 14 and 28. Safety included vital signs, clinical chemistry, haematology and adverse events (AEs). All AEs were resolved by the end of the study period or upon subsequent follow up, and out of range laboratory values and changes in vital signs were deemed not clinically relevant following AlphaWave® L-Theanine supplementation. Participants supplemented with AlphaWave® L-Theanine had decreases of 12.92% (p = 0.051) and 17.98% (p = 0.04) in PSS scores after 14 and 28days, respectively, while those on placebo had respective decreases of 9.74% (p = 0.061) and 17.88% (p = 0.009). There were no significant differences between groups for change in salivary cortisol. The AlphaWave® L-Theanine group demonstrated decreased time asleep after 28days and significantly reduced light sleep after 14 and 28days compared to placebo (p ≤ 0.040). The AlphaWave® L-Theanine group significantly improved by 21.79% and 21.33% in Stroop test correct reaction time after 14 and 28days, respectively, while those on placebo improved after 28days only (p = 0.005). AlphaWave® L-Theanine supplementation for 28days was safe and significantly decreased perceived stress significantly decreased perceived stress and light sleep, improved sleep quality and enhanced cognitive attention in the studied population. Larger, randomized controlled trials with longer duration of AlphaWave® L-Theanine supplementation are warranted to reduce inter-individual variability and the potential placebo effect. ClinicalTrials.gov identifier, NCT05808595.

Immunomodulating effects of the single bacterial strain therapy EDP1815 on innate and adaptive immune challenge responses-a randomized, placebo-controlled clinical trial.

The gut microbiome can modulate systemic inflammation and is therefore target for immunomodulation. Immunomodulating effects of EDP1815, a bacterial commensal strain of Prevotella histicola, were studied in healthy participants. Effects on adaptive immunity were evaluated by a neo-antigen challenge with keyhole limpet haemocyanin (KLH), while effects on innate immunity were evaluated by topical toll-like receptor 7 (TLR7) agonist imiquimod. Capsules with two enteric coating levels (EC1, EC2) were compared.Thirty-six healthy participants were included and received a daily dose of 8 × 1010 cells EDP1815-EC1, EDP1815-EC2 or placebo (randomization 1:1:1) for 60 days. They received KLH vaccinations at days 8, 24 and 36, with intradermal skin challenge at day 57. KLH challenge outcomes were antibody levels, and skin blood flow and erythema after skin challenge, measured by imaging techniques. Imiquimod administration started at day 57, for 72 h. Outcomes consisted of imaging measurements similar to the KLH challenge, and the influx of inflammatory cells and cytokines in blister fluid.There was no effect of EDP1815 treatment on the KLH challenge, neither on the imaging outcomes of the imiquimod challenge. There was a consistently lower influx of inflammatory cells in the blister fluid of EDP1815-treated participants (neutrophils, p = 0.016; granulocytes, p = 0.024), more pronounced in EC1. There was a lower influx of interleukin [IL]-1β, IL-6, IL-8, IL-10, interferon [IFN]-γ and tumour necrosis factor in blister fluid of EDP1815-treated participants.EDP1815 had immunomodulatory effects on the innate immune response driven by imiquimod, but no effect on the KLH challenge was observed. Trial registration number: NCT05682222; date: 22 July 2022.

A randomized, double-blind, placebo-controlled study on immune improvement effects of ethanolic extract of Echinacea purpurea (L.) Moench in Korean adults.

Echinacea purpurea (L.) Moench (EP), a medicinal plant native to North America, is now cultivated in various regions including Europe. With increasing popularity of Echinacea in Korea recently, a human clinical trial was conducted to evaluate immune-enhancing efficacy and safety of EP 60% ethanolic extract (EPE) in Koreans. Eighty volunteers were recruited for this randomized, double-blind, placebo-controlled clinical trial. They were randomly divided into two groups and given either a daily dose of 200 mg of EPE or a placebo. All participants underwent testing for Natural Killer (NK) cell cytotoxic activity, serum cytokine levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, TNF-α), Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), and Multidimensional Fatigue Scale (MFS) during this study to assess changes in outcomes. After 8 weeks of EPE consumption, a significant increase in NK cell cytotoxic activity compared to the placebo was observed. Additionally, serum cytokine levels of IL-2, IFN-γ, and TNF-α also significantly increased following EPE consumption. However, no significant changes were observed in WURSS-21 and MFS before and after EPE consumption. Throughout the 8-week study period, no adverse reactions were reported in relation to EPE consumption, and there were no clinically significant changes in diagnostic laboratory tests or vital signs in the EPE group. These results indicate that consumption of EPE could lead to immune improvement without any adverse effects. This clinical trial was the first to demonstrate beneficial effects of EPE consumption on immunity in Korean adults.

A 4-week Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Use of Grape Seed Extract for Reducing Plasma Glucose, Lipid Profile, and Blood Pressure in Patients with Type 2 Diabetes Mellitus

: Diabetes mellitus (DM) is a common chronic disease that can significantly decrease life expectancy due to its complications. Grapes (Vitis Vinifera L.) and their byproducts, including seeds, have been used globally to treat various ailments. In this clinical trial, we investigated the effect of Iranian grape seed extract (GSE) on fasting blood sugar (FBS), lipid profile [including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG)], as well as systolic and diastolic blood pressure (SBP and DBP, respectively) in patients with type 2 DM (T2DM). Seventy-four patients with T2DM were divided into two groups; 38 patients in the treatment group received 263.2 mg of GSE (standardized to contain 250 mg of proanthocyanidine) twice daily, and 36 patients in the placebo group received 263.2 mg of placebo twice daily for thirty days. At the end of the intervention, a statistically significant decrease was observed in SBP [from 125.83 ± 13.39 in the placebo group to 121.94 ± 7.49 in the treatment group (P = 0.002]), and FBS [from 144.75 ± 30.82 in the placebo group to 129.87 ± 31.79 in the treatment group (P = 0.001)]. There were no significant changes in total cholesterol, HDL, LDL, TG, and DBP between the two groups. Consuming Iranian GSE for a short duration can lower FBS and systolic blood pressure (BP), suggesting that GSE may play a key role in improving BP and fasting blood glucose in patients with T2DM.

Effect of nano-curcumin supplementation on angina status, and traditional and novel cardiovascular risk factors in overweight or obese patients with coronary slow flow phenomenon: a randomized double-blind placebo-controlled clinical trial

BackgroundCardiovascular events and poor quality of life are frequently observed in patients with coronary slow flow phenomenon (CSFP). This trial evaluated the effect of nano-curcumin supplement containing curcuminoids, as multifunctional nutraceuticals, on angina status, and some traditional and novel cardiovascular risk factors in overweight or obese patients with CSFP.MethodsIn this double-blind, randomized, placebo-controlled clinical trial, 42 overweight or obese patients with CSFP received either 80 mg/day of nano-curcumin or placebo for 12 weeks. Seattle angina questionnaire (SAQ) as a clinical measure of angina status, circulating endocan, adropin, homocysteine, lipid profile, and the novel scores of visceral adiposity index (VAI) and waist-triglyceride index (WTI) were assessed before and after the intervention. The independent samples t-test, Mann-Whitney test, analysis of covariance, Chi-square, and Fisher’s exact tests were used where appropriate.ResultsAll domains of SAQ including physical limitation, angina stability, angina frequency-severity, treatment satisfaction, and disease perception and quality of life improved significantly in the nano-curcumin compared with the placebo group. No significant changes were observed in serum endocan, adropin, and homocysteine following the intervention. Triglycerides, triglyceride/high-density lipoprotein cholesterol ratio, WTI and VAI values improved significantly only within the nano-curcumin group.ConclusionsSupplementation with 80 mg/day nano-curcumin (containing curcuminoids) for 12 weeks significantly improved clinically important disease-specific aspects of health in patients with CSFP. Some traditional and novel cardiovascular risk factors improved significantly only compared with the baseline values, which need further investigation.Trial registrationThis study was approved by the Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1398.794). The study protocol was registered at Iranian Registry of Clinical Trials by IRCT20131125015536N8 registration ID at 19.06.2019.

The effect of probiotic-fortified kefir on cardiovascular risk factors in elderly population: a double-blind, randomized, placebo-controlled clinical trial

IntroductionThe outbreak of cardiovascular disease (CVD) augments with age. Gut dysbiosis can worsen or initiate systemic disorders such as metabolic diseases and CVDs. Therefore, this research aimed to assess the effect of kefir fortified with Lactobacillus helveticus R0052 and Bifidobacterium longum R017 on CVD risk factors in the elderly population. The subjects of this study were selected from the Motahari Clinic in Shiraz, Iran.MethodThis study was a double-blind, randomized, and controlled clinical trial that was conducted on 67 elderly people who were randomly divided into two groups: the fortified kefir group (n = 32), which received one bottle of fortified kefir (240 cc), and the placebo group (n = 35), which received one bottle of regular kefir for eight weeks. To analyze the data, SPSS software was applied.ResultsAfter eight weeks, significant differences were seen in atherogenic and Castell’s risk index I between the fortified and regular groups (p = 0.048 and p = 0.048, respectively). No significant differences were found in Castelli’s risk index II, high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides (TG), non-HDL-C, TG-cholesterol index, and fasting blood sugar by comparing the two groups.ConclusionOur investigation demonstrated that fortified kefir with probiotics did not significantly affect lipid profiles. Still, it could significantly affect some indices, including Castelli’s risk index I and atherogenic index. More studies are required to confirm the findings and mechanisms of probiotics’ effect on CVD risk factors.Trial numberThe present registered at the Iranian Registry of Clinical Trials (IRCT20130227012628N3) at 2023-02-21.

Assessment of the Impact of RNase in Patients With Severe Fatigue Related to Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): A Randomized Phase 2 Trial of RSLV-132.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and RNA debris persist in viral reservoirs for weeks to months following infection, potentially triggering interferon production and chronic inflammation. RSLV-132 is a biologic drug composed of catalytically active human RNase1 fused to human IgG1 Fc and is designed to remain in circulation and digest extracellular RNA. We hypothesized that removal of SARS-CoV-2 viral RNA from latent reservoirs may improve inflammation, neuroinflammation, and fatigue associated with post-acute sequelae of SARS-CoV-2 infection (PASC). This was a phase 2, double-blind, placebo-controlled randomized clinical trial in participants with a 24-week history of PASC and severe fatigue. The primary endpoint of the trial assessed the impact of 6 intravenous doses of RSLV-132 on the mean change from baseline at day 71 in the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue SF 7a). A statistically significant difference on day 71 was not observed with respect to the primary or secondary endpoints. This was likely due to a placebo response that increased during the trial. Statistically significant improvement in fatigue as measured by the PROMIS Fatigue SF 7a, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and Physicians Global Assessment (PGA) instruments were observed earlier in the trial, with women demonstrating greater responses to RSLV-132 than men. While fatigue was not statistically significantly improved at Day 71, earlier timepoints revealed statistically significant improvement in fatigue and physician global assessment. The data suggest eliminating latent viral RNA by increasing serum RNase activity may improve fatigue in PASC patients. Women may respond better to this approach than men. Future studies will aim to confirm these findings.

Safety, Tolerability, and Outcomes of Tafamidis for the Treatment of Acquired Amyloid Neuropathy in Domino Liver Transplant Recipients.

Acquired amyloid neuropathy is an iatrogenic disease that appears years after a domino liver transplant. The objectives of our study are to analyze the efficacy and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. This post-authorization, prospective, longitudinal study included seven domino liver transplant recipients with acquired amyloid neuropathy who received treatment with tafamidis for 18months. The primary endpoints were the response rate, defined as those patients with an increase of<2 points on the Neurological Impairment Score (NIS) from baseline, and the change in the NIS score from baseline. Secondary endpoints included the Quantitative Sensory Test, 10-m walk test, quality of life (Norfolk), and disability (Rasch-built Overall Disability Scale). As safety parameters, the evidence of graft rejection, changes in immunosuppressive trough levels and changes in antiviral and allogeneic cellular immunity before and 12months after tafamidis treatment were also assessed. Six patients (85.7%) had responded at 18-months. Compared to baseline, we observed non-statistically significant improvement in mean NIS score at 6months (- 2.54 points, CI - 5.92 to 0.84), 12months (- 3.25 points; CI - 6.63 to 0.13), and 18months (- 2.35 points; CI - 5.74 to 1.02). Changes in the Quantitative Sensory Test, 10-m walk tests and the quality of life and disability questionnaires were not statistically significant. The use of tafamidis did not induce relevant side effects or drug interactions. Also, no acute rejections events nor changes in functional adaptive immunity were observed. Our study supports the safety and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. Tafamidis shows promise as a useful treatment in the clinical management of these patients. Future randomized placebo-controlled clinical trials with longer follow-up durations are needed.

Antibiotic prophylaxis may effectively reduce early failures after beginner-conducted dental implant surgery.

A randomized, double-blind, placebo-controlled clinical trial. To assess the impact of antibiotic prophylaxis on postoperative recovery and implant short-term survival in clinically healthy patients who underwent placement of 2-4 dental implants by inexperienced operators. The study adhered to the ethical guidelines of theHelsinki declaration, and followed the CONSORT protocol for randomized controlled trials (RCTs). Signed consent forms were provided by all patients. Included were healthy individuals aged over 18 years, with sufficient and fully healed alveolar ridge (undergone extraction at least 3 months prior), requiring placement of 2-4 dental implants, and were classified as ASA I or II. Exclusion criteria were: systemic diseases, hypersensitivity to penicillin, pregnancy or lactation, smoking, recent antibiotic usage, and history of periodontitis. Patients were randomly allocated into 2 groups: the antibiotic group received 1 g of amoxicillin one hour before surgery, while the placebo group was given starch-filled capsules that looked identical to the antibiotic. All implants were installed through 2-stage procedures by students of a specialization course in implant surgery, employing a standardized procedure and armamentarium. Each patient was evaluated preoperatively, and at 2 days and 7 days postoperatively, for the following parameters: mouth opening, experienced pain (using a visual analog scale), and signs of infection (fistula, wound ulceration, tissue necrosis, flap dehiscence, and purulent exudates). Implant survival was monitored for up to 90 days after implant surgery. A total of 90 patients (224 implants) were included: 43 patients (108 implants) in the antibiotic group, and 47 patients (116 implants) in the placebo group. Overall, there were 58 women and 32 men, aged from 23 to 70 years old. In terms of mouth opening, pain, and infection parameters, no statistically significant differences were observed between the groups at any of the time points evaluated. Similarly, there was no statistically significant difference regarding antibiotic usage and implant loss at the patient level (p = 0.06). However, at the implant level, significantly higher implant loss rate was noted in the placebo group (14.9%) compared to the antibiotic group (2.3%) [p < 0.05]. Prophylactic antibiotic administration effectively reduced the occurrence of implant loss after implant surgery performed by inexperienced practitioners.

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.

Phase III Randomized, Placebo-Controlled Clinical Trial of Donepezil for Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy (WF-97116).

To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy. Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo. Cognition and self-report cognitive functioning was assessed at baseline, 12, 24 (end of intervention), and 36 (washout) weeks postrandomization. Mixed-effects repeated measures analysis of covariance models were used to assess treatment differences in immediate recall (primary outcome) on the Hopkins Verbal Learning Test-Revised (HVLT-R) and other cognitive domains (secondary outcomes) with covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification, and an unstructured covariance matrix to account for within participant correlation over time. Two hundred seventy-six BCS from 87 NCORP practices (mean age, 57.1, standard deviation [SD], 10.5) who were at a mean of 29.6 months (SD, 14.2) postchemotherapy were randomly assigned to donepezil (n = 140) or placebo (n = 136). At 24 weeks, treatment groups did not differ on HVLT-R scores (donepezil mean = 25.98, placebo = 26.50, P = .32). There were no statistically significant differences between treatments at 12, 24, or 36 weeks for attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Endocrine therapy and menopausal status did not affect results. BCS 1-5 years after completing chemotherapy with documented memory problems, randomly assigned to 24 weeks of 5-10 mg of donepezil once daily, did not perform differently at the end of treatment on tests of memory, other cognitive functions, or subjective functioning than those randomly assigned to placebo.

The efficacy of curcumin supplementation on serum total antioxidant capacity, malondialdehyde, and disease activity in women with rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial.

Oxidative stress plays a crucial role in the physiopathology of rheumatoid arthritis (RA), which is associated with impaired antioxidant defenses. This study aimed to investigate the effects of curcumin supplementation on serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and disease activity in women with RA. In this clinical trial, 48 women with RA were treated with one capsule of curcumin (500 mg daily) or placebo for 8 weeks. Anthropometric measurements and fasting blood samples were collected at baseline and end of the study. Finally, we assessed the Disease Activity Score in 28 joints (DAS-28), dietary intake, and physical activity levels. While curcumin supplementation for 8 weeks significantly increased the serum levels of TAC (p < 0.05), it decreased tender joint counts, swollen joint counts, visual analog scale (VAS) for pain, and DAS-28 compared to the placebo at the end of the study (p < 0.001 for all). MDA levels significantly decreased in the curcumin group (p < 0.05). However, changes in MDA concentration were not significant between groups at the end of the trial (p = 0.145). Curcumin supplementation had a beneficial effect on increasing the serum levels of TAC and decreased DAS-28 in women with RA.

Impact of intraoperative dexmedetomidine on postoperative delirium and pro-inflammatory cytokine levels in elderly patients undergoing thoracolumbar compression fracture surgery: A prospective, randomized, placebo-controlled clinical trial.

This study evaluates the efficacy of dexmedetomidine (DEX) in reducing postoperative delirium (POD) and modulating pro-inflammatory cytokines in elderly patients undergoing thoracolumbar compression fracture surgery. In this randomized, double-blind, placebo-controlled trial conducted from October 2022 to January 2023 at Anting Hospital in Shanghai, 218 elderly patients were randomized into DEX (n = 110) and normal saline (NS, n = 108) groups. The DEX group received 0.5 µg/kg/h DEX, and delirium incidence was assessed using the Confusion Assessment Method (CAM) on days 1 to 3 post-surgery. Levels of interleukins IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were measured pre-operation (T0) and on postoperative days 1 (T1) and 3 (T3). Preoperative (T0) and postoperative day 1 (T1) cerebrospinal fluid (CSF) samples were treated with varying concentrations of olanzapine or DEX to observe their regulatory effects on the expression of Phospho-ERK1/2 and Phospho-JNK. Dexmedetomidine significantly lowered the incidence of POD to 18.2%, compared to 30.6% in the NS group (P = .033). While all patients showed an initial increase in cytokine levels after surgery, by T3, IL-6 and TNF-α levels notably decreased in the DEX group, with no significant change in IL-1β levels across groups. The adverse events rate was similar between groups, demonstrating the safety of DEX in this population. In postoperative CSF samples, treatment with 0.5 mM DEX significantly downregulated Phospho-JNK and upregulated Phospho-ERK1/2 expression, demonstrating a dose-dependent modulation of inflammatory responses. Dexmedetomidine is effective in reducing early POD in elderly patients post-thoracolumbar compression fracture surgery. It also decreases IL-6 and TNF-α levels, indicating its potential in managing postoperative inflammatory responses. Treatment with 0.5 mM DEX significantly modulated Phospho-ERK1/2 and Phospho-JNK expressions in postoperative CSF samples, indicating a dose-dependent effect on reducing inflammation. This study contributes to understanding DEX's role in improving postoperative outcomes in elderly patients.

Cedirogant in adults with psoriasis: a phase 2, randomized, placebo-controlled clinical trial.

Dysregulated interleukin (IL)-17/IL-23 signaling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage program. To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. In this phase 2b, multicenter, double-blind, 16-week study (NCT05044234), adults aged 18-65 years were randomized 1:1:1:1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg, or placebo. Assessments included ≥50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician Global Assessment 0/1, Psoriasis Symptoms Scale 0, and improvements in itch, adverse events (AEs), pharmacokinetics, and IL-17A/F levels. Efficacy results based on observed cases were summarized descriptively. Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early due to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 28.6%, 7.7%, and 41.7% in the cedirogant 75 mg, 150 mg, and 375 mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75 mg, 150 mg, and placebo groups and higher in the cedirogant 375-mg group; most AEs were mild or moderate. Patients with psoriasis who received cedirogant showed PASI improvement and cedirogant was generally well tolerated. Results should be interpreted in the context of early study termination. Cedirogant development has been discontinued.

Safety of deer antler extract in children: A 12-week randomized controlled clinical trial.

Deer antlers have been used as strong tonifying medicine in Asian countries, especially for the growth and development of children in pediatrics of Korean medicine. The safety of deer antler in adults cannot be applied directly to children because of their physiological characteristics. To accumulate reliable data on the safety of deer antler in pediatric populations, well-designed clinical studies are required. This research is a 12-week, randomized, double-blind, placebo-controlled clinical trial evaluating the safety of deer antler extract (DAE) in children. The DAE group received an intervention containing 1586 mg of DAE, whereas the control group received a placebo for 12 weeks. The safety was assessed by monitoring adverse drug reactions (ADRs) and laboratory test results. One hundred participants were included in the safety analysis. Three and 2 participants in the DAE and control groups, respectively, reported ADRs. There was no significant difference in incidence between the 2 groups. ADRs are categorized into gastrointestinal and skin-related symptoms. No serious ADR was observed throughout the study. The laboratory test results were within or outside the normal range at clinically insignificant levels. The research discovered that the DAE is safe in terms of ADRs and laboratory parameters under the conditions studied. Further studies are required to accumulate safety data about DAE dosage adjustment and potential interactions with other medicines.

Abstract PS07-03: Randomized trials of oestrogen-alone and breast cancer incidence: a meta-analysis

Abstract Background Findings from cohort studies compared with those from the Women's Health initiative (WHI) randomized, placebo-controlled clinical trial regarding estrogen-alone and breast cancer risk are discordant. The WHI randomized trial enrolled 10,729 postmenopausal women with prior hysterectomy, mean age 64 years (33.2% 50-59), no prior breast cancer and a non-suspicious baseline mammogram. After 7.2 years intervention and 16.2 years cumulative follow-up, conjugated equine estrogen (CEE)-alone (vs placebo) significantly reduced breast cancer incidence by 22% (P = 0.005) and significantly reduced breast cancer mortality by 40% (P = 0.04) (Chlebowski JAMA 2020). In contrast, cohort studies had opposite findings, estrogen-alone use was associated with significantly higher breast cancer incidence and significantly higher breast cancer mortality. Therefore, we identified all available estrogen-alone randomized clinical trials where breast cancer findings were reported to conduct a meta-analysis examining the totality of the randomized clinical trial evidence regarding estrogen-alone influence on breast cancer incidence. Methods We conducted PubMed and Google Scholar searches on randomized trials and: estrogen, hormone therapy, and breast cancer, and searches from a prior meta-analyses and reviews. In the current meta-analysis, for trials with published relative risks (RR) and 95% confidence intervals (CI), each log-RR was multiplied by weight = 1/V, where V = variance of the log-RR, and V was derived from the corresponding 95% CI. For smaller trials with only breast cancer numbers, a different method was used, the corresponding log-RR = (O – E)/weight, where O is the observed case number in the oestrogen-alone group and E the corresponding expected case number, E = nP. Findings Ten randomized trials, incorporating WHI findings, and findings from nine smaller trials included 14,272 randomized participants and 591 incident breast cancers. Of 9 smaller trials, 6 required negative baseline screening mammograms; mean entry age: 50 to 56 years in 5 trials and 62 to 71 years in 4 trials. In the nine smaller trials, 1.2% (24 of 2029) vs 2.2% (33 of 1514) randomized to estrogen-alone vs placebo (open label, one trial) were diagnosed with breast cancer, respectively (RR 0.65 95% CI 0.38-1.11, P = 0.12). For 5 trials evaluating estradiol formulations, RR = 0.63 95% CI 0.34-1.16, P = 0.15. In the WHI trial, 4.5% (238 of 5310) vs 5.5% (296 of 5429) randomized to estrogen-alone were diagnosed with breast cancer, respectively (RR 0.78 95% CI 0.65-0.93, P = 0.005)). Combining smaller trials and WHI results, 3.6% (262 of 7339) vs 4.7% (329 of 6943) randomized to estrogen-alone vs placebo were diagnosed with breast cancer, respectively (overall RR 0.77 95% CI 0.65-0.91, P = 0.002). Results from a sensitivity analysis for the smaller trials using exact conditional logistic regression were essentially unchanged (RR 0.64 95% CI 0.35-1.13). Interpretation The totality of randomized clinical trial evidence supports a conclusion that estrogen-alone use, among postmenopausal women with prior hysterectomy, significantly reduces breast cancer incidence. This consistent pattern seen in these randomized trials suggests the WHI CEE-alone findings are not “stand alone” outcomes or due to chance. Citation Format: Rowan Chlebowski, Aaron Aragaki, Kathay Pan, Joanne Mortimer, Karen Johnson, Jean Wactawski-Wende, Meryl LeBoff, Sayeh Lavasani, Dorothy Lane, Rebecca Nelson, JoAnn Manson. Randomized trials of oestrogen-alone and breast cancer incidence: a meta-analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS07-03.

Pycnogenol® French maritime pine bark extract in randomized, double-blind, placebo-controlled human clinical studies.

Pycnogenol® French maritime pine bark extract is a well-known and thoroughly studied patented extract from the bark of Pinus pinaster Ait. ssp. Atlantica. In 39 randomized double-blind, placebo-controlled (RDP) human clinical trials including 2,009 subjects, Pycnogenol® French maritime pine bark extract supplementation for two weeks to six months has been shown to beneficially affect cardiovascular health, chronic venous insufficiency, cognition, joint health, skin health, eye health, women's health, respiratory health and allergies, oral health and sports performance. The mechanisms of action that can explain the respective effects on different conditions in the human body are discussed as well. As investigated in several in vitro, in vivo and in clinical studies, Pycnogenol® French maritime pine bark extract showed antioxidative effects, anti-inflammatory abilities, beneficial effects on endothelial function and reinforcing effects on the extracellular matrix. The present review aims to give a comprehensive overview of currently available "gold standard" RDP trials of Pycnogenol®'s benefits across various health domains compared to placebo. In addition, some of the processes on which the presented effects of Pycnogenol® French maritime pine bark extract are based will be elucidated and discussed. This broad overview of RDP studies on Pycnogenol® in different health domains can be used as a basis for further research on applications and mechanisms of this unique French maritime pine bark extract.

Comparative analysis of the drugs efficacy for carbohydrate metabolism early disorders (prediabetes) treatment: A review

In the contemporary reality pharmacological correction of the early carbohydrate metabolism disorders is the main method for the type 2 diabetes prevention. Taking into account the main role of insulin resistance in the prediabetes development it can be supposed that pharmacological agents directly activating the insulin receptor are the pathogenic-base therapy for prediabetes treatment. Such kind of this pathogenic therapy is Subetta® – a representative of the class of biological drugs created using the based graduated technology. Due to the absent of the direct comparative trials of Subetta® versus metformin in the efficacy of the type 2 diabetes prevention in prediabetes patients, was performed an analysis of the effectiveness of these two drugs using the adjusted indirect comparison method of the results of the randomized double-blind placebo-controlled clinical trial of Subetta® efficacy and safety in impaired glucose tolerance patients with the results of several metformin studies similar in inclusion and efficacy criteria. The results indicate greater Subetta® efficacy in the treatment of glucose intolerance and metformin's – in the impaired fasting glucose treatment, which can be explained by the differences in the action mechanisms of these two drugs for prediabetes treatment.