Cts-Clinical and Translational Science最新文献

{"title":"Surfing the T Wave: A Primer on ECG T Wave Morphologies Encountered in Clinical Trials and Impact on the QT Interval and Patient Safety","authors":"Robert M. Lester,&nbsp;Sabina Paglialunga","doi":"10.1111/cts.70145","DOIUrl":"https://doi.org/10.1111/cts.70145","url":null,"abstract":"<p>Electrocardiogram (ECG) interpretation and measurement is an essential aspect of patient safety and pharmacovigilance in clinical trials. Changes in the T wave segment of an ECG can provide both diagnostic and prognostic information and may be affected by a variety of intrinsic and extrinsic factors related to drug administration. To add, regulators in their guidance encourage sponsors to provide analysis on treatment-emergent T wave morphology changes when submitting clinical study reports. Despite the T wave representing an important element of an ECG and impacting QT interval measurement, there is often a lack of recognition and incomplete understanding of the different T wave configurations that would affect subject management. Moreover, this topic has not been formally incorporated in pharmaceutical research. Therefore, this comprehensive review aims to profile normal and abnormal T wave morphologies that scientists and principal investigators might encounter during study conduct that would influence patient management and safety. This includes commentary on T wave pathophysiology, prognostic information, and short- and long-term management strategies when T wave abnormalities are present.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Safety Profile of SNS812, a First in Human Fully Modified siRNA Targeting Wide-Spectrum SARS-CoV-2, in Healthy Subjects","authors":"Yi-Chung Chang,&nbsp;Yi-Fen Chen,&nbsp;Chi-Fan Yang,&nbsp;Hui-Ju Ho,&nbsp;Jen Fu Yang,&nbsp;Yuan-Lin Chou,&nbsp;Ching-Wen Lin,&nbsp;Pan-Chyr Yang","doi":"10.1111/cts.70202","DOIUrl":"10.1111/cts.70202","url":null,"abstract":"<p>Severe acute respiratory syndrome caused by the coronavirus (SARS-CoV-2) in the COVID-19 pandemic has highlighted the need for effective treatments, as rapid viral mutations complicate therapeutic development. SNS812, a fully modified inhaled siRNA that targets the conserved RNA-dependent RNA polymerase (RdRP) gene of SARS-CoV-2, has been shown to possess its suppression ability against wide-spectrum SARS-COV-2 variants preclinically. To evaluate the safety and tolerability of inhaled SNS812 in healthy participants, a randomized, double-blind, placebo-controlled phase 1 trial was conducted. To justify the first-in-human inhalation study, this research was divided into two parts: single ascending doses (0.3, 0.6, and 1.2 mg/kg) and multiple doses (0.6 and 1.2 mg/kg) of daily inhalation for seven consecutive days to assess the safety, tolerability, immunogenicity, and pharmacokinetics of SNS812. Of the 44 participants, 3 in the 0.3 mg/kg single-dose group, 2 in the 1.2 mg/kg multiple ascending doses group, and 1 in the placebo group reported treatment-emergent adverse events (TEAEs). No serious adverse events (SAEs), treatment-related adverse events (TRAEs), or TEAEs caused discontinuation or deaths were observed. PK showed rapid absorption of SNS812, with peak concentrations (median <i>T</i>_max) reached at 1.5–2 h, and an elimination half-life (t _1/2) between 4.96 and 7.08 h. No antidrug antibodies (ADAs) were detected in either group. The results demonstrated that the first-in-human, fully modified with wide-spectrum anti-SARS-COV2 siRNA by inhalation following a single dose and multiple doses was safe and well tolerated in healthy participants.</p><p><b>Trial Registration:</b> NCT05677893</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nontraditional Factors Influencing Cardiovascular Disease Risk: Correlation Among Framingham Risk Score, Body Composition Index, and Sleep-Breathing Monitoring Index","authors":"Libo Zhao,&nbsp;Xin Xue,&nbsp;Yinghui Gao,&nbsp;Weimeng Cai,&nbsp;Zhe Zhao,&nbsp;Dong Rui,&nbsp;Tingyu Nie,&nbsp;Tianjiao Li,&nbsp;Cong Ma,&nbsp;Li Fan,&nbsp;Lin Liu","doi":"10.1111/cts.70170","DOIUrl":"https://doi.org/10.1111/cts.70170","url":null,"abstract":"<p>To examine the correlation among body composition, sleep-breathing indicators, and Framingham risk score (FRS) to identify and amplify nontraditional factors that influence the risk of CVD in males, A total of 195 male participants underwent examinations for body composition and sleep-breathing monitoring. We compared the differences in individual factors across various FRS groups. We further conducted multiple linear regression analysis. A cutoff value of FRS ≥ 14 was utilized, and potential influencing factors were examined by logistic regression analysis. Statistical differences were observed in the levels of fasting blood glucose (FBG), CO₂, serum ferritin, hemoglobin (HB), and ECT/TBW among the FRS tripartite groups. However, no significant differences were found in AHI and MSpO₂. The multiple linear regression analysis revealed positive correlations between ECW/TBW and FBG with FRS (<i>β</i> = 0.324 and 0.324, <i>p</i> &lt; 0.001), while HB and muscle/fat mass exhibited negative correlations with the score (<i>β</i> = −0.185 and − 0.169, <i>p</i> &lt; 0.01). These five factors—ECW/TBW, FBG, HB, serum ferritin, and muscle/fat mass—collectively accounted for 28.6% of the variation in FRS. A higher ECW/TBW was significantly associated with FRS ≥ 14 (OR = 2.208, 95% CI: 1.503–3.244). Conversely, reduced levels of muscle/fat mass, HB, and basal metabolic rate (BMR) were significantly linked to moderate-to-high CVD risk (OR_ratio = 0.532, 95% CI: 0.284–0.996; OR_HB = 0.961, 95% CI: 0.932–0.991; OR_BMR = 0.997, 95% CI: 0.995–1.000). This study revealed correlations among ECW/TBW, HB, FBG, and muscle-to-fat mass ratio with the risk of CVD predicted using FRSs.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Informing Implementation Strategies for Pharmacogenomics in Cancer: Development of Survey Tools for Healthcare Professionals and Consumers","authors":"Marliese Alexander,&nbsp;Chiao Xin Lim,&nbsp;Senthil Lingaratnam,&nbsp;Sarah Glewis,&nbsp;Joanne Wickens,&nbsp;Abbey Hird,&nbsp;Zi Yue Chen,&nbsp;Alistair Bozkurt,&nbsp;Amit Khot,&nbsp;David Routledge,&nbsp;Sam Harris,&nbsp;Craig Underhill,&nbsp;Ashley Whitechurch,&nbsp;Lydia Leong,&nbsp;Marcus Pergolini,&nbsp;Gail Rowan,&nbsp;Monnette Samo,&nbsp;Chloe Georgiou,&nbsp;Peter Savas,&nbsp;Jenny Devine,&nbsp;Alysia Kepert,&nbsp;Safeera Y. Hussainy","doi":"10.1111/cts.70144","DOIUrl":"https://doi.org/10.1111/cts.70144","url":null,"abstract":"<p>Integration of clinical pharmacogenomics (PGx) within routine cancer care is limited despite frequent use of medicines impacted by PGx, evidence for the benefits of PGx, and the availability of international PGx clinical guidelines. Our study objective was to develop survey tools to assess PGx knowledge, attitudes, practices, perceptions, and education needs among (a) doctors, nurses, and pharmacists involved in cancer care (healthcare professionals, HCPs) and (b) adults who have received cancer treatment or their carers (consumers), with the view to informing implementation strategies for PGx in solid and hematologic cancers. Survey tools were developed in a three-phase (ph) mixed-methods approach. Content was informed by systematic literature review findings and framed by determinants of behavior as informed by the Theoretical Domains Framework (ph-1). Refinement occurred through four separate priority partnership meetings (ph-2). Meetings focused on clinical PGx practices within select cancer streams, and consumers' knowledge, attitudes, and preferences for PGx testing. Content/face validity and health literacy (Flesch Kincaid Grade Level) assessments informed final refinements (ph-3). Separate HCP and consumer survey tools were developed with six common sections: (1) introduction; (2) demographics; (3) experience; (4) knowledge, attitudes, practices and perceptions; (5) education; and (6) vignettes. Content and face validity were rated highly with acceptable health literacy assessments for questions within the consumer survey (median grade level 6; range 1–8). The developed survey tools will be used to generate evidence to inform local implementation strategies for PGx in cancer and promote broader integration of pharmacogenomics in routine clinical care.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Selective Serotonin Reuptake Inhibitors on Coagulation: Fact or Fiction?","authors":"Antoine Mokhtarian,&nbsp;Sophie Melicine,&nbsp;Virginie Siguret,&nbsp;Georges Jourdi","doi":"10.1111/cts.70164","DOIUrl":"https://doi.org/10.1111/cts.70164","url":null,"abstract":"<p>Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety yet are associated with an increased bleeding risk. While this risk is mainly linked to the decrease in platelet serotonin content, thus abnormal platelet functions, some studies suggest an inherent effect of SSRIs on coagulation. Hence, we performed a literature review to provide an overview of the different studies assessing SSRI's effects on coagulation assays routinely used in clinical practice. A search of the PubMed database yielded 22 relevant studies. Results were inconsistent: While some studies showed minor changes in routine coagulation assays, namely, prothrombin time and activated partial thromboplastin time, the majority found no significant effects of SSRIs on coagulation tests. Then, we specifically investigated the impact of citalopram, a commonly prescribed SSRI, on the thrombin generation assay (TGA) allowing the detection of any potential procoagulant or anticoagulant effect. TGA was performed in platelet-poor plasma from 14 healthy volunteers spiked with citalopram at therapeutic (0.1 and 0.5 μM) and supratherapeutic (50 μM) concentrations. TGA parameters were not significantly changed compared to the control condition regardless of the citalopram concentration. All in all, our findings failed to demonstrate any compromised coagulation function associated with SSRI therapy.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Pharmacokinetics in Rats Using Machine Learning: A Comparative Study Between Empirical, Compartmental, and PBPK-Based Approaches","authors":"Moritz Walter,&nbsp;Ghaith Aljayyoussi,&nbsp;Bettina Gerner,&nbsp;Hermann Rapp,&nbsp;Christofer S. Tautermann,&nbsp;Pavel Balazki,&nbsp;Miha Skalic,&nbsp;Jens M. Borghardt,&nbsp;Lina Humbeck","doi":"10.1111/cts.70150","DOIUrl":"https://doi.org/10.1111/cts.70150","url":null,"abstract":"<p>A successful drug needs to combine several properties including high potency and good pharmacokinetic (PK) properties to sustain efficacious plasma concentration over time. To estimate required doses for preclinical animal efficacy models or for the clinics, in vivo PK studies need to be conducted. Although the prediction of ADME properties of compounds using machine learning (ML) models based on chemical structures is well established in drug discovery, the prediction of complete plasma concentration–time profiles has only recently gained attention. In this study, we systematically compare various approaches that integrate ML models with empiric or mechanistic PK models to predict PK profiles in rats after intravenous administration prior to synthesis. More specifically, we compare a standard noncompartmental analysis (NCA)-based approach (prediction of CL and V_ss), a pure ML approach (non-mechanistic PK description), a compartmental modeling approach, and a physiologically based pharmacokinetic (PBPK) approach. Our study based on internal preclinical data shows that the latter three approaches yield PK profile predictions of comparable accuracy across a large data set (evaluated as geometric mean fold errors for each profile of over 1000 small molecules). In summary, we demonstrate the improved ability to prioritize drug candidates with desirable PK properties prior to synthesis with ML predictions.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Profiles of Lansoprazole in Patients With Morbid Obesity Post-Roux-en-Y Gastric Bypass Surgery","authors":"Suthep Udomsawaengsup,&nbsp;Sathienrapong Chantawibul,&nbsp;Naranon Boonyuen,&nbsp;Sarunnuch Panyavorakhunchai,&nbsp;Pattharasai Kachornvitaya,&nbsp;Wasu Wisanuyothin,&nbsp;Pittawat Somvanapanich,&nbsp;Warittha Lertwatthiphong,&nbsp;Napatsanan Tanathitiphuwarat,&nbsp;Pajaree Chariyavilaskul","doi":"10.1111/cts.70200","DOIUrl":"https://doi.org/10.1111/cts.70200","url":null,"abstract":"<p>Data on the effects of Roux-en-Y gastric bypass (RYGB) surgery on lansoprazole pharmacokinetics in morbidly obese patients are limited. This study aimed to evaluate the impact of RYGB surgery on the pharmacokinetic profile of lansoprazole in Thai morbidly obese patients. Participants received 30 mg of lansoprazole twice daily for 7 days before surgery and continued the regimen for 6 weeks post-surgery. Plasma lansoprazole concentrations were measured at predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 h after dosing, both pre- and post-surgery, using a validated high-performance liquid chromatography technique. <i>CYP2C19</i> genotyping classified participants as normal metabolizers (<i>*1</i>/<i>*1</i>) or intermediate metabolizers (<i>*1</i>/<i>*2</i> and <i>*1</i>/<i>*3</i>). Pharmacokinetic parameters, including the area under the plasma concentration-time curve from 0 to 8 h (AUC_0–8 h), maximum plasma concentration (Cmax), and time to maximum concentration (Tmax), were compared before and after surgery. A total of 13 patients (mean age 37.0 ± 3.9 years; body mass index 54.0 ± 4.8 kg/m²) were enrolled. Post-surgery, AUC_0–8 h and Cmax decreased by 16% (<i>p</i> = 0.009) and 31% (<i>p</i> = 0.003), respectively, while Tmax remained unchanged. A 30% reduction in Cmax (<i>p</i> = 0.007) was observed in <i>CYP2C19</i> normal metabolizers, whereas no significant changes were noted in intermediate metabolizers. In conclusion, RYGB surgery significantly reduced lansoprazole systemic exposure, particularly in <i>CYP2C19</i> normal metabolizers. Further studies are needed to explore the clinical implications of these pharmacokinetic changes and develop optimized treatment strategies for post-RYGB patients.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: TCTR20220118001</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspectives on Using Pharmacogenomics to Guide Tobacco Cessation: Survey Results From an American Indian Community","authors":"Madeline L. Wichman,&nbsp;Daniela M. Wall,&nbsp;Suzanna S. Garcia Mota,&nbsp;Shayna R. Killam,&nbsp;Karen E. Brown,&nbsp;Kaja Aagaard,&nbsp;Juanita Swaney,&nbsp;LeeAnna I. Muzquiz,&nbsp;Bernadette N. Corum,&nbsp;Katrina G. Claw,&nbsp;Erica L. Woodahl","doi":"10.1111/cts.70194","DOIUrl":"https://doi.org/10.1111/cts.70194","url":null,"abstract":"<p>Pharmacogenomics research has predominantly focused on populations of European ancestry, limiting the application to diverse populations such as American Indian and Alaska Native (AIAN) communities. Our community-centric study aims to understand perspectives on utilizing pharmacogenomics to guide tobacco cessation in an AIAN community using a survey with qualitative and quantitative components. We assessed participant (<i>n =</i> 273) tobacco usage and cessation history, pharmacogenomics knowledge, and perceptions of utilizing pharmacogenomics in the context of tobacco cessation. We found that the majority of participants (92%) were aware of the risks associated with tobacco usage and believed it to be a problem within their community (76%). Our results showed that 29% of participants had some level of knowledge regarding pharmacogenomics and only 6% had previously participated in pharmacogenomics research, demonstrating the need for further education and awareness. Community involvement was a priority for participants, with 64% preferring Tribal inclusion in all research stages and 63% favoring partnerships with local health centers. We also found support for future research, with 68% viewing pharmacogenomics as a beneficial tool. Concerns were raised regarding the handling of genetic material and result dissemination, emphasizing the importance of ethical research practices, transparent communication, and community partnership. Our findings serve as a foundation for shaping future research efforts and developing a framework for implementing tobacco cessation interventions. Our community-centered approach addresses the specific needs of this AIAN community and offers insights applicable to research practices within other underserved and marginalized populations, particularly those with a historical distrust of research.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-In-Human Safety, Tolerability, and Pharmacokinetics of PPI-1011, a Synthetic Plasmalogen Precursor","authors":"Tara Smith,&nbsp;Kaeli J. Knudsen,&nbsp;Shawn A. Ritchie","doi":"10.1111/cts.70195","DOIUrl":"https://doi.org/10.1111/cts.70195","url":null,"abstract":"<p>PPI-1011 is a synthetic plasmalogen precursor designed to augment plasmalogen levels in patients with Rhizomelic chondrodysplasia punctata (RCDP), an ultra-rare genetic disorder caused by a plasmalogen deficiency that results in significant physical and mental delays. We report here a Phase I, randomized, double-blind, placebo-controlled study that evaluated the safety, tolerability, and pharmacokinetics (PK) of single (10–100 mg/kg) and multiple (75 and 100 mg/kg/day) ascending doses of PPI-1011 in healthy adults. All treatment-emergent adverse events (TEAEs) were mild, monitorable, and resolved without intervention, suggesting no significant safety concerns. The most common TEAEs were gastrointestinal in both the placebo and PPI-1011 groups, suggesting they were likely related to the oil-based nature of the formulation. PK analysis confirmed that both single (25, 50, 75 and 100 mg/kg) and multiple-dose (75 and 100 mg/kg, once daily) administration of PPI-1011 significantly increased serum levels of the target plasmalogen (PlsEtn 16:0/22:6). With a once-daily regimen, PPI-1011 administration resulted in a sustained increase of PlsEtn 16:0/22:6 serum concentrations in healthy participants over a duration of 14 days and beyond.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Effect of Epigallocatechin Gallate (EGCG) in Reducing Folate Levels in Reproductive Aged Women by MTHFR and DHFR Genotype in Combination With Letrozole or Clomiphene","authors":"Jeremy J. Johnson,&nbsp;Hiba Siblini,&nbsp;Ayman Al-Hendy,&nbsp;James H. Segars,&nbsp;Frank González,&nbsp;Hugh S. Taylor,&nbsp;Bhuchitra Singh,&nbsp;Sandra A. Carson,&nbsp;Gregory M. Christman,&nbsp;Hao Huang,&nbsp;Bikash Dangi,&nbsp;Heping Zhang","doi":"10.1111/cts.70189","DOIUrl":"https://doi.org/10.1111/cts.70189","url":null,"abstract":"<p>Previous epidemiological studies have suggested that green tea catechins, including Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, may be associated with reduced serum folate levels. This is of particular interest as women of childbearing age may be consuming EGCG from tea, dietary supplements, or involved in active clinical trials studying EGCG or green tea extract. EGCG was reported to shrink uterine fibroids in preclinical and clinical studies. This observation led to the development of a multicenter NICHD-funded clinical trial to evaluate the safety of EGCG for treating women with fibroids and unexplained infertility (NCT04177693). To answer the question of whether green tea extract standardized to EGCG led to a reduction in folate, 39 women aged ≥ 18 to ≤ 40 years, with/without uterine fibroids, were evaluated. These women were randomized to receive either EGCG, EGCG + clomiphene, or EGCG + letrozole for 30 days. A daily dose of 720 mg of highly characterized green tea extract containing EGCG was used. Participants were genotyped for polymorphisms at positions 677 and 1298 in MTHFR and for the −19 bp deletion polymorphism of DHFR. During the intervention with EGCG, folate levels remained in the normal range in all subjects. Our data suggest that in reproductive-age women, a 30-day course of EGCG 720 mg daily taken alone or in combination with clomiphene citrate or letrozole (for 5 days) is well-tolerated and is not associated with folate deficiency even in the presence of MTHFR and/or DHFR polymorphisms known to negatively impact folate synthesis.</p><p><b>Trial Registration:</b> Clinical trial: NCT 01311869</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}