Current Clinical Trials Research Articles

Current clinical trials on gastric cancer surgery in China

Current clinical trials on gastric cancer surgery in China

Recent Therapeutic Advancements for Gaucher Disease

AbstractGaucher Disease (GD) is a well‐known lysosomal storage disease resulting from mutations in the GBA1 gene. GD exhibits a range of clinical manifestations, each with unique symptoms and severity levels. This review explores the genetic foundations of GD, highlighting the significance of Glucocerebrosidase (GCase) deficiency, resulting in the skeletal complications associated with GD, such as osteonecrosis, fractures, and bone pain, all of which significantly negatively influence the quality of life for patients. Over 700 mutations in the GBA1 gene are found to cause variations in gene expression in GD, indicating the disease's complexity and the need for continued research. Early diagnosis and prognosis evaluation depend heavily on diagnostic approaches integrating laboratory assessments, genetic testing, and clinical symptoms. Treatment strategies like enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) have advanced, but issues like high costs and invasiveness still exist. This review focuses on novel therapeutic approaches that show promise in treating GD, including gene and cell‐based therapies, pharmacological chaperone therapy (PCT), and drug delivery via nanoparticles. Finally, discussions on current clinical trials, limitations of the advanced therapies, and future scope are summarized.

Impact of L-carnitine supplementation on gastric emptying and bowel function in pediatric ketogenic diet therapy: a clinical trial.

Ketogenic diet (KD) is an excess fat, enough protein, and minimal carbohydrate diet. The high fat content in KD lowers the oesophageal sphincter tone, slows gastric emptying, and decreases intestinal transit time. The primary aim of the current clinical trial was to study the effect of L-carnitine supplementation on gastric emptying in children with drug resistant epilepsy (DRE) on KD. Assessment of the protective effect of L-carnitine on bowel function and habits in those patients was a secondary aim. The current study recruited 30 patients aged 12 months to 18 years newly diagnosed with DRE assigned to start KD who were following up at the Pediatric Clinical Nutrition and Neurology Outpatient Clinics or were admitted due to DRE at the Pediatric Neurology Inpatient Department, Children's Hospital, Ain Shams University (Egypt). Participants were assigned randomly into 2 arms; arm I: received KD with L-carnitine supplementation, arm II: received KD only. Patients were assessed at baseline and after 3 months of starting KD, the assessments of children included: 24-hour dietary recall, Chalfont Seizures Severity Scale, gastrointestinal symptoms score and Bristol stool chart, frequency of defecation per week, anthropometric measurements assessment, fasting serum lipid profile and measurement of the antral length by ultrasound. There was significant increase in antral length in the patients who received KD with L-carnitine supplementation compared to the non-supplemented group. The antral length showed a significant negative correlation with GI symptoms score in all cases and the L-carnitine supplemented group. It also showed a significant positive correlation with Bristol stool score in all patients and a significant positive correlation with stool frequency in the L-carnitine supplemented group only. L-carnitine supplementation to children with DRE on KD has a significant role in improving gastric motility and it increases the frequency of defecation. Further studies are recommended to explore additional benefits, meanwhile it is prudent to advise L-carnitine supplementation for such patients.

PCSK9 inhibitors in the management of atherosclerotic cardiovascular disease: Current clinical trials and future directions

PCSK9 inhibitors in the management of atherosclerotic cardiovascular disease: Current clinical trials and future directions

Recent Advances in Biomaterial‐Based Scaffolds for Guided Bone Tissue Engineering: Challenges and Future Directions

ABSTRACTBone tissue engineering (BTE) has emerged as a promising approach for the regeneration and repair of bone defects caused by trauma, disease, or aging. This review provides an overview of recent advancements in BTE, with a focus on the development and application of biomaterial‐based scaffolds, including natural (e.g., collagen, chitosan), synthetic (e.g., polylactic acid [PLA], polycaprolactone [PCL]), and composite materials (e.g., hydroxyapatite‐based composites). It discusses their properties, benefits, and limitations. Additionally, this review examines innovative fabrication strategies such as 3D printing, electrospinning, and freeze‐drying, which enhance scaffold customization and performance. This review aims to provide insights into future directions of BTE research and its potential applications in regenerative medicine. Functionalization strategies, including surface modifications, coating, and the incorporation of growth factors and cells, are reviewed for their roles in improving scaffold bioactivity. In vivo and in vitro research have demonstrated the therapeutic promise of these scaffolds, while current clinical trials offer insights into their translational use. Challenges facing the translation of these technologies into clinical practice are also highlighted.

Advancements in Gene Therapy for Human Disease: Trend of Current Clinical Trials

Advancements in Gene Therapy for Human Disease: Trend of Current Clinical Trials

Natural killer cell engagers: From bi-specific to tri-specific and tetra-specific engagers for enhanced cancer immunotherapy.

Innovative NKCEs: NK cell engagers (NKCEs) represent a promising new class of immunotherapeutics targeting tumours by activating NK cells. Multi-specific formats: The transition from bi-specific to multi-specific NKCEs enhances their versatility and therapeutic efficacy. NKCEs have the potential to improve NK cell activation by engaging activating receptors and incorporating cytokines. Current clinical trials demonstrate the safety and efficacy of various NKCEs across different cancer types. Future research directions: Optimising NKCE designs and exploring combination therapies are essential for overcoming challenges in cancer treatment.

Comparison of the effect of self-care education with two methods, teach-back and smartphone application, on the adherence to treatment in patients with inflammatory bowel disease.

Self-care is one of the basic principles in the management of chronic diseases, which influences follow-up and adherence to treatment. Therefore, the current study was conducted with the aim of comparing the effect of teach-back (TB) and a smartphone application on adherence to treatment in patients with inflammatory bowel disease (IBD). The current clinical trial was conducted among 80 patients with IBD in Mashhad, Iran, in 2021-2022. Self-care education (diet, personal and social relationships, medications, sleep, physical activity, sexual relationships, etc.) was provided through TB method in one group and by using a smartphone application in another group. The control group only received the routine education. A checklist for demographic information and the adherence questionnaire in patients with chronic diseases were used for data collection. Patients' mean age was 38.73 ± 10.32 years. The majority of patients had ulcerative colitis (81%) and were married (67%). Mean and standard deviation score of adherence to treatment were the same in all three groups before the intervention (P = 0.668). The mean post-test scores of adherence to treatment in the TB, application, and control groups were 170.04 ± 14.19, 167.99 ± 11.59, and 159.60 ± 10.94, respectively. The difference was statistically significant (P = 0.003). A significant difference was observed in regards to the mean post-test scores of adherence to treatment between TB and control groups (P = 0.004) and app and control groups (P = 0.048). However, the difference between TB and app groups was not significant (P = 0.989). TB method and smartphone application have the same effect on adherence to treatment in patients with IBD. Due to the usability and cost-effectiveness of smartphone applications, this method can be used by health-care providers to educate this group of patients.

Treatment with flozins across the whole spectrum of heart failure in Poland between February 2022 and June 2023 based on Heart Failure Observational Study by Polish Cardiac Society.

Abstract Since the introduction of the ESC guidelines in 2021 and the increased level of recommendations in 2023, SGLT2 inhibitors (SGLT2i) have been widely used in all patients with heart failure (HF), improving their prognosis. Current guidelines recommend the use of SGLT2i across the entire spectrum of HF regardless of ejection fraction. The aim of the study was to summarize the usage of SGLT2i in patients with HF in Poland, based on data gathered in the Heart Failure Observational Study (HEROES) conducted by the Polish Cardiac Society. Overall, 1176 patients (enrolled between Feb 2022 and Jun 2023) were included in the analysis (hospitalizations: N=918, outpatient visits: N=258). Most of them were men (71.7%) with a median age of 69 years (IQR: 60-75). Patients with reduced ejection fraction (HFrEF) were the most numerous group (48%, N=565) followed by preserved (HFpEF, 22%, N=259) and mildly reduced (HFmrEF, 14%, N=166) ejection fraction. In 16% of cases, ejection fraction was not reported. Only fewer than 60% of subjects were reported to be treated with SGLT2i (overall: 59.5%; HFrEF: 82.3%; HFmrEF: 48.8%, HFpEF: 32.4%). We divided the whole study group into 4 even quartiles based on the number of consecutive patients enrolled (Q1: Feb 2022-Dec 2022; Q2: Sep 2022; Q3: Mar 2023; Q4: Jun 2023). Results showed an overall increasing number of patients treated with SGLT2i in consecutive quartiles, especially in HFmrEF group (Fig. 1). However, in the last quartile (Q4), less than 40% usage of SGLT2i in HFpEF patients was observed (38.2%). The analyzed period ended before the release of the 2023 focused update of HF guidelines that strengthened recommendations for SGLT2i use to the first class of recommendations regardless of ejection fraction. This document will probably further increase the usage of SGLT2i in the Polish HF population. Nevertheless, our data are worrying, as overall more than 1/3 of HF patients in the last quartile were not treated with one of the basic and effective drugs in HF. It is worth mentioning that the 2021 HF guidelines recommended SGLT2i in the first class of recommendations only in HFrEF, but by that time, current clinical trial results had already shown great benefit in HFmrEF and HFpEF patients.SGLT2i treatment in PL (Feb2022-Jun2023)

Regulation of HTT mRNA Biogenesis: The Norm and Pathology.

Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of the CAG repeat in exon 1 of the HTT gene, leading to the formation of a toxic variant of the huntingtin protein. It is a rare but severe hereditary disease for which no effective treatment method has been found yet. The primary therapeutic targets include the mutant protein and the mutant mRNA of HTT. Current clinical trial approaches in gene therapy involve the application of splice modulation, siRNA, or antisense oligonucleotides for RNA-targeted knockdown of HTT. However, these approaches do not take into account the diversity of HTT transcript isoforms in the normal conditions and in HD. In this review, we discuss the features of transcriptional regulation and processing that lead to the formation of various HTT mRNA variants, each of which may uniquely contribute to the progression of the disease. Furthermore, understanding the role of known transcription factors of HTT in pathology may aid in the development of potentially new therapeutic tools based on endogenous regulators.

Unraveling the potential biomarkers of immune checkpoint inhibitors in advanced ovarian cancer: a comprehensive review.

The ongoing research on the role of immunotherapy in advanced ovarian cancer (OC) and current clinical trials indicate that patients shown limited response to immune checkpoint inhibitor (ICI) monotherapy. When combined with other treatments or drugs, the efficacy of immunotherapy will be significantly improved. Biomarkers can be used to identify patients with better responses, thereby improving the precision and efficacy of immunotherapy. Key biomarkers for advanced OC include homologous repair deficiency, programmed death-ligand (PD-L) 1 expression, chemokines, and tumor infiltrating lymphocytes. These biomarkers could be applied in the future to select the most suitable patient populations. This review comprehensively examines the research and development of biomarkers in OC immunotherapy from three omics perspectives: genomics, transcriptomics, and proteomics, which may provide guidance for the effectiveness of OC immunotherapy strategies.

Self-efficacy in patients with inflammatory bowel disease: the effect of self-care education by two randomized methods-teach-back and a smartphone application.

The use of the best teaching method to promote self-care in patients with inflammatory bowel disease (IBD) has not been well defined. Therefore, the current study was conducted to compare the effect of self-care education by two methods of teach-back and a smartphone application. The current clinical trial with a pre- and post-test design was conducted among 78 patients with IBD. Patients were allocated to three groups of application, teach-back and control using a simple blocked randomization. Data were collected using a checklist for demographic information and Inflammatory Bowel Disease Self-efficacy Scale. Collected data were analyzed using SPSS. Participants in all three groups were homogeneous in terms of demographic variables. The mean pretest scores of self-efficacy (SE) in the application, teach-back and control groups were 191.37 ± 49.15, 193.92 ± 45.54 and 192.76 ± 43.12, respectively. The mean post-test scores of SE in the application, teach-back and control groups were 224.51 ± 49.89, 207.48 ± 48.109 and 189.92 ± 40.28, respectively (P = 0.033). The results of the current study showed that self-care education by the application can better improve the mean scores of SE and its four dimensions of managing stress and emotions, managing symptoms and disease, managing medical care and maintaining remission, compared to other methods. It seems that the use of the application as a continuous and cost-effective educational strategy will become widespread in the future for patient education among most healthcare and treatment systems.

Patient-Derived Organoids: A Game-Changer in Personalized Cancer Medicine.

Research on cancer therapies has benefited from predictive tools capable of simulating treatment response and other disease characteristics in a personalized manner, in particular three-dimensional cell culture models. Such models include tumor-derived spheroids, multicellular spheroids including organotypic multicellular spheroids, and tumor-derived organoids. Additionally, organoids can be grown from various cancer cell types, such as pluripotent stem cells and induced pluripotent stem cells, progenitor cells, and adult stem cells. Although patient-derived xenografts and genetically engineered mouse models replicate human disease in vivo, organoids are less expensive, less labor intensive, and less time-consuming, all-important aspects in high-throughput settings. Like in vivo models, organoids mimic the three-dimensional structure, cellular heterogeneity, and functions of primary tissues, with the advantage of representing the normal oxygen conditions of patient organs. In this review, we summarize the use of organoids in disease modeling, drug discovery, toxicity testing, and precision oncology. We also summarize the current clinical trials using organoids.

TARGETED THERAPY IN DIFFUSE INTRINSIC PONTINE GLIOMA: A COMPREHENSIVE REVIEW OF MONOCLONAL ANTIBODIES

Abstract AIMS Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor, marked by its poor prognosis and frequent recurrence despite conventional therapy. Our review examines the molecular landscape of DIPG, highlighting key factors driving tumor progression. We evaluate the therapeutic potential of various monoclonal antibodies (mAbs) targeting these factors, providing insights into their mechanisms and ongoing clinical trials. Our aim is to guide future investigations and immunotherapeutic strategies for DIPG. METHOD A narrative review was conducted using the PubMed database to identify relevant review articles, clinical trials, and observational studies published within the past 10 years, focusing on the use of mAbs in DIPG. The search terms “monoclonal antibodies”, “diffuse intrinsic pontine glioma”, and “targeted therapy” were employed. Additionally, a search was conducted on clinicaltrials.gov to gather information on ongoing and completed clinical trials. RESULTS Current human clinical trials on the checkpoint inhibitors anti-PD-1 (Nivolumab, Pembrolizumab, Balstilimab, Cemiplimab), anti-PD-L1 (Durvalumab), and anti-CTLA-4 (Ipilimumab, Zalifrelimab) have not demonstrated significant improvement in overall patient survival. One major limitation has been the small sample size and limited expression of such markers in DIPG. Conversely, combination therapies involving anti-VEGF (Bevacizumab) and anti-EGFR (Nimotuzumab and Cetuximab) have shown promising results in small sample studies, but these results are not conclusive. Trials on anti-CD276 (Omburtamab) and CD40 agonist (APX005M) have shown no specific clinical or tumor outcomes in DIPG. Newer emerging agents like anti-TIM3 and anti-IL13Ra2 have shown very favorable results in in-vivo and in-vitro studies. CONCLUSION Current evidence is insufficient to support the use of mAbs in DIPG. More large-size studies investigating the combinations of checkpoint inhibitors with different therapeutic agents are needed. Additionally, the promising results seen with anti-VEGF and anti-EGFR mAbs in their respective combination therapies warrant exploration in large-scale studies to draw more accurate conclusions. Furthermore, human trials should be conducted on anti-TIM3 and anti-IL13Ra2.

Dysphagia and Muscle Weakness Secondary to Botulinum Toxin Type A Treatment of Cervical Dystonia: A Drug Class Analysis of Prescribing Information.

The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R2) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R2 = 0.74; muscle weakness = 0.096, R2 = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY®, Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia.

Microbial Therapeutics in Oncology: A Comprehensive Review of Bacterial Role in Cancer Treatment.

Conventional cancer therapies, including chemotherapy, radiotherapy, and immunotherapy, have significantly advanced cancer treatment. However, these modalities often face limitations such as systemic toxicity, lack of specificity, and the emergence of resistance. Recent advancements in genetic engineering and synthetic biology have rekindled interest in using bacteria as a novel therapeutic approach in oncology. This comprehensive review explores the potential of microbial therapeutics, particularly bacterial therapies, in the treatment of cancer. Bacterial therapies offer several unique advantages, such as the ability to selectively target and colonize hypoxic and necrotic regions of tumors, areas typically resistant to conventional treatments. The review delves into the mechanisms through which bacteria exert antitumor effects, including direct tumor cell lysis, modulation of the immune response, and delivery of therapeutic agents like cytotoxins and enzymes. Various bacterial species, such as Salmonella, Clostridium, Lactobacillus, and Listeria, have shown promise in preclinical and clinical studies, demonstrating diverse mechanisms of action and therapeutic potential. Moreover, the review discusses the challenges associated with bacterial therapies, such as safety concerns, immune evasion, and the need for precise targeting, and how recent advances in genetic engineering are being used to overcome these hurdles. Current clinical trials and combination strategies with conventional therapies are also highlighted to provide a comprehensive overview of the ongoing developments in this field. In conclusion, while bacterial therapeutics present a novel and promising avenue in cancer treatment, further research and clinical validation is required to fully realize their potential. This review aims to inspire further exploration into microbial oncology, paving the way for innovative and more effective cancer therapies.

Outcome of Patients Transplanted for C3 Glomerulopathy and Primary Immune Complex-Mediated Membranoproliferative Glomerulonephritis

IntroductionAround 50% of C3 glomerulopathy and primary immune-complex-mediated membranoproliferative glomerulonephritis (C3G, IC-MPGN) patients reach kidney failure at 10 years after diagnosis. Since these patients are generally young, the majority will be listed for kidney transplantation. However, reported outcomes in patients transplanted for C3G and IC-MPGN are heterogeneous and conflicting, as they are mainly based on retrospective monocentric studies. We thus aimed to provide detailed multicenter data on these patients, taking advantage of the ongoing nationwide Swiss Transplant Cohort Study. MethodsWe analyzed patient and graft outcome, including the risk of graft loss in relation to recurrence of glomerulopathy. ResultsForty-one (10 C3G, 31 IC-MPGN) transplanted recipients were included with a mean age at transplantation of 48+16 years. Living donation provided 53% of the organs. During a mean follow-up of 4.7 years, 7 patients (4 C3G, 3 IC-MPGN) presented disease recurrence with a mean time to recurrence of 1.2 years. New-onset or rapidly increasing proteinuria was an early marker of recurrence, preceding significant decline in eGFR. Following recurrence, 28% lost their graft, compared to 11% of patients without recurrence. Disease recurrence was the primary cause of graft loss in all patients. Finally, 14% of patients died during follow-up. ConclusionThis study provides important insights into the epidemiology and outcome of C3G and IC-MPGN patients and their grafts after kidney transplantation. The data also suggest that proteinuria may serve as an early biomarker of disease recurrence and should be considered in patient management as well as an endpoint in current clinical trials using novel complement modulators.

The effects of selenium administration on mean platelet volume, neutrophil-to-lymphocyte ratio, and red cell distribution width in critically ill older adults: A double-blinded randomized clinical trial

BackgroundLow serum Selenium (Se) levels in critical patients have been associated with poor clinical outcomes and higher mortality rates. The purpose of this study was to investigate the effect of Se administration on mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (N/L), and red cell distribution width (RDW) in older adults admitted to the intensive care unit (ICU). MethodThis study was a double-blinded randomized clinical trial. Critically ill patients were randomly divided into two groups of Se and placebo. The Se group (N=30) initially received 3000 mg of Se at once within 3 hours, followed by a dose of 1500 mg daily for 10 days as a one-hour infusion. The control group (N=30) received normal saline for 10 days. A venous blood sample was collected on the first and 10th day. Statistical analysis was performed using SPSS.26 statistical software. To analyze quantitative data in two groups, based on the estimated normality, an independent t-test was used. P value less than 0.05 was considered statistically significant. ResultsOn day 10, the MPV value in the Se group was significantly lower compared to the placebo group (9.32 ± 1.78 and 10.43 ± 2.06, respectively, p = 0.03). Within the Se group, contrary to the controls, the MPV value decreased significantly from day 1 to day 10 (p<0.001). Further, the RDW value in the Se group was significantly lower compared to the placebo group (13.77 ± 1.57 and 15.32 ± 2.42, respectively, p = 0.005). The N/L ratio remained similar between the two groups before and after the intervention. ConclusionOur findings suggest that Se can affect the MPV and RDW parameters in older adults hospitalized in the ICU. However, further studies with a larger population are necessary to support these findings. Clinical Relevancy StatementThe effects of selenium administration on hematological parameters in older adults admitted to the ICU are not well-established. There is limited direct evidence linking serum selenium levels to erythrocyte and hemoglobin stability in humans. The current clinical trial promotes the current literature and shows that selenium holds potential in management of the older ICU patients.

Cell therapy for neurological disorders.

Cell therapies for neurological disorders are entering the clinic and present unique challenges and opportunities compared with conventional medicines. They have the potential to replace damaged nervous tissue and integrate into the brain or spinal cord to produce functional effects for the lifetime of the patient, which could revolutionize the way clinicians treat debilitating neurological disorders. The major challenge has been cell sourcing, which historically relied mainly on fetal brain tissue. This has largely been overcome with the advent of pluripotent stem cell technology and the ability to make almost any cell of the nervous system at scale. Furthermore, advances in gene editing now allow the generation of genetically modified cells that could perform better and evade the immune system. With all the remarkable new approaches to treat neurological disorders, we take a critical look at the state of current clinical trials and how challenges may be overcome with the evolving technology and innovation occurring in the stem cell field.

Ewing Sarcoma in the Pediatric Population: Predictors of Survival Within the United States.

Bone and joint tumors are the third most common cause of pediatric cancer-related deaths in the United States. Although there have been improvements in survival rates among pediatric cancer patients over the past few decades, bone and joint cancers remain the exception. Considering current clinical trials involving novel targeted therapies, the establishment of updated mortality rates and predictors of survival for this cancer would be prudent. This investigation sought to determine updated 5-year survival rates and predictors of survival among pediatric Ewing sarcoma (ES) of bone treated within the United States. The National Cancer Database was retrospectively inquired for all pediatric ES cases within the most updated bone and joint public use file available in September 2022. The reported data were truncated to only include patients with reported 5-year vital (ie, survival) status. Cox proportional hazard regression was conducted on both the truncated data and the entire cohort to validate the findings. The patients were then separated into alive versus deceased cohorts, and univariate regression analysis was done followed by multivariable regression of notable variables of interest. Overall, an aggregated 5-year survival rate of 74.5% was found in the included patient cohort. Patients with localized cancer had a comparatively improved 5-year survival rate of 84.70% as opposed to those with macrometastatic disease on presentation with a survival rate of 50.4%. Patient demographic-, tumor-, and treatment-specific variables all demonstrated an effect on survival. The multivariable predictors of worse mortality were found to include older age, larger tumor size (>8 cm), macrometastatic disease on presentation, and positive surgical margins. This analysis serves to establish updated survival rates of pediatric ES treated within the United States to set standards for comparison among future studies. Continued multi-institutional and international collaboration is needed to optimize current treatment results and develop novel targeted therapies.