Reviews on Recent Clinical Trials - Online First

Clinical trial regulations are essential for ensuring the safety, efficacy, and ethical conduct of drug development. However, the regulatory frameworks governing these trials vary significantly across different countries, affecting approval processes, trial conduct, and drug development timelines. By comparing clinical trial regulations and trial management practices, this study aims to identify regulatory challenges and propose improvements to enhance global harmonization.

This review examines clinical trial regulations across the United States, European Union, Australia, and India, selected based on their diverse regulatory frameworks and global influence on clinical research. Literature screening was conducted using PubMed, Scopus, and official regulatory agency websites, focusing on publications from 2016 to 2024. Selection criteria included regulatory frameworks, amendments, ethical guidelines, and compliance measures related to clinical trials. The analysis covered key aspects such as trial approval timelines, safety reporting requirements, cost implications, and oversight mechanisms to identify regulatory challenges and potential improvements.

The findings reveal that although the studied countries maintain strict regulatory frameworks, they still exhibit gaps and inconsistencies. For instance, variations in approval timelines, safety reporting standards, and oversight mechanisms create inefficiencies and delays in drug development. It notes the absence of specific regulations for Clinical Research Organizations (CROs) authorization and herbal medicine trials in most regions.

Therefore, a key recommendation is to certify CROs to enhance the credibility of clinical trials. Additionally, specific regulations for herbal medicine trials are required to ensure safety and efficacy. Ethical concerns, particularly in pediatric and orphan drug research, demand more stringent oversight. The integration of blockchain technology is also proposed to improve accountability in drug development. Overall, promoting global regulatory harmonization is essential to minimize delays in patient access to essential therapies. These insights are intended to guide policymakers, researchers, and stakeholders in enhancing the quality, safety, and accessibility of medicines.

This review underscores the importance of consistent, transparent, and adaptable clinical trial regulations across global jurisdictions. While current frameworks demonstrate a commitment to ethical and scientific rigor, targeted reforms, such as CRO recognition, herbal trial regulation, and technology integration, are important for advancing clinical research. A harmonized regulatory landscape not only accelerates drug development but also ensures timely patient access to innovative and life-saving therapies.

Among premenopausal women, polycystic ovarian syndrome (PCOS) is one of the most ubiquitous endocrine and metabolic conditions. Abdominal adiposity, insulin resistance, obesity, metabolic diseases, and cardiovascular hazards are often associated with PCOS. This investigation aims to decipher the influence of oral Vitamin D3 supplementation (2000 IU/day for three months) on glucose metabolism in PCOS women.

123 subjects (females 16 to 40 years of age) were arbitrarily allocated to three cohorts (n = 41 in each cohort) Each participant received two tablets daily and a sachet every month for three months (Group I: Vitamin D3 Tablets + placebo sachets; Group II: Placebo Tablets + Vitamin D3 sachets; Group III: Tablets + Placebo sachets).

Among 123 PCOS subjects, 93.4% exhibited hypovitaminosis D. The baseline 25-hydroxyvitamin D (25(OH)D) concentration of 13.76 (SD ± 10.61) ng/ml increased by 86.84% post-intervention. Groups I and II (active group) depicted substantial diminution in pre-treatment fasting and 2-h blood glucose, with no substantial change in the HOMA-IR. Group III (placebo) showed no improvement in vitamin D status or HOMA-IR. Overall, we observed no substantial HOMA-IR improvement with vitamin D subjunction. However, subgroup analysis revealed a statistically significant enhancement in HOMA-IR for subjects achieving a two-fold upsurge in post-supplementation 25(OH)D levels (≥ 20 ng/ml) compared to those without this increase (p = 0.025).

The cohort’s mean blood 25-hydroxyvitamin D concentrations were successfully boosted by 84% by Vitamin D3 dosage; yet, the influence on insulin resistance markers displayed a subtle complexity. A relationship was found amid the absolute variation in HOMA-IR and the percentage variation in Vitamin D. Nevertheless, there was no substantial general alteration in the mean HOMA-IR across different subgroups.

Vitamin D3 supplementation improves glucose metabolism, as demonstrated by lower fasting and 2-hour blood glucose levels, but overall has no substantial repercussion on measures of insulin sensitivity like HOMA-IR. A larger vitamin D3 dose and an extended follow-up study are essential to comprehend the complex physiology of vitamin D and glucose homeostasis.

Radiotherapy for breast cancer has a clear benefit for long-term survival and local control rate. However, it can negatively impact a patient’s quality of life by affecting healthy surrounding normal tissues, including the heart and lungs. This study aimed to clarify the contribution of echocardiography with Global Longitudinal Strain (GLS) to early radiation-induced cardiotoxicity detection.

A prospective study was conducted on 25 early-stage left-sided breast cancer patients. All underwent 2D strain echocardiography before and one year after RT. Normality was assessed using the Shapiro-Wilk test and box plots. The Wilcoxon signed-rank test was conducted to compare GLS values. A statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 25.

Mean Global Longitudinal Strain value before and one year after radiotherapy was -20.2% and -21.2%, respectively. In half of these cases, the values ranged from -19.65% to -22.70% before radiotherapy and between -18.8% and -22.25% after radiotherapy. The non-parametric Wilcoxon test indicated no statistically significant difference before and after radiotherapy (Ζ = 0.902, p = 0.367).

Although no statistically significant reduction in GLS was observed one year post-radiotherapy, a decrease was noted in patients receiving higher cardiac doses, suggesting potential early subclinical myocardial changes. Strain echocardiography shows promise as a sensitive tool for the early detection of radiation-induced cardiotoxicity, warranting further research with larger cohorts and extended follow-up.

While this small cohort study did not show significant GLS changes post-RT, it highlights the need for larger studies with longer follow-ups to confirm the role of strain imaging in identifying early cardiotoxicity in breast cancer patients.

Significant advancements have been achieved with the use of targeted molecular therapies for the treatment of Soft Tissue Sarcomas (STS). However, data remain scarce about the potential benefits and toxicity of this therapeutic option. In this narrative review, we aim to better clarify the potential wound healing complications in STS patients undergoing neoadjuvant (NA) radiotherapy (RT) combined with targeted therapies.

We used the PubMed database to retrieve journal articles, and the inclusion criteria were all studies that illustrated the potential RT toxicity, combined with targeted therapies, in the NA setting of STS patients.

Our search resulted in seven studies that fulfilled the inclusion criteria. Delayed wound complication rates were observed similarly to RT alone, while one study reported intolerable toxicity without referring specifically to wound complications.

The combination of RT with targeted therapies in STS seems to be effective and well tolerated. Due to the lack of studies with a high level of evidence, further research is required to enhance the existing knowledge for its potential value in this field.

Sexual health is an essential part of women's lives at different ages. Pregnancy, childbirth, and breastfeeding can affect women's sexual function by inducing biological, psychological, and social changes. Due to the prevalence of sexual dysfunction in lactating women and the effects of reflexology therapies on it, this study was conducted to investigate the effect of foot reflexology on the sexual function of lactating women.

This randomized clinical trial was conducted in selected health centers of Isfahan in 2022 on 64 lactating women (32 women in each group of intervention and control). The samples were selected using the convenience sampling method and were randomly divided into two groups with a random number table. Each participant in the intervention group received 10 sessions of foot reflexology, and each session lasted for 50 minutes (25 minutes for each foot) and was held every three days. The female sexual function index (FSFI) questionnaire was completed before the intervention and four weeks after the end of it. The control group received routine care and completed the questionnaire before the intervention and 9 weeks later. Data were analyzed using SPSS version 20 and independent/paired t-tests.

Data analysis showed that the subjects of the two groups were homogeneous in demographic and fertility characteristics at the beginning of the study. The total mean score of sexual function in the intervention group was 20.36 ± 4.16 before the intervention and 28.05 ± 2.89 after the intervention. In the control group, this score was 20.51 ± 3.75 before the intervention and 20.54 ± 3.71 nine weeks after it. A comparison of the total mean score of sexual function and dimensions showed a significant difference between the two groups four weeks after the intervention (p <0.001). In the intervention group, significant changes were observed in the total mean score of sexual function and its dimensions four weeks after the intervention compared to before the intervention. However, in the control group, there were no significant changes in this score and its dimensions nine weeks later compared to before the intervention.

Based on the results of this study, lactating women in the two groups did not have a desirable sexual function before the intervention. However, foot reflexology in the present study could effectively improve the sexual function of women in the reflexology group. Therefore, it is recommended to employ foot reflexology therapy in health centers to help lactating women restore their sexual function.

IRCT20210814052180N1.

Millions of people worldwide suffer from dry eye disease. Dry eye, a multifunctional condition of the ocular surface, typically occurs in conjunction with an unbalanced tear film. With increasing age, the dry eye problem becomes worse. Aqueous-deficit dry eye and evaporative dry eye are the two traditional classifications for dry eye. Various examination tools are used to diagnose dry eye. Clinical trials are conducted in four phases to check the safety and efficacy of drugs. The quick clearance from the precorneal space is ensured by the eye's advanced defense mechanism. It restricts the integrated medicine's entry into the eyes, resulting in a usually low bioavailability for topical eyedrops. In this study, we focus on recently developed formulations for curing dry eye.

This review's goal was to outline the etiology, clinical discovery and development, patents, and recent advancements for dry eye disease.

The current study has described the widespread incidence of dry eye, which was found to be more common as people aged and recently developed formulations are treating dry eyes. According to research, novel formulations are enhancing ocular drug delivery.

In this review, etiology, clinical data, dry eye formulation patents, and recent advancements are all included.