Pisa

Researchers are exploring the use of intraoral ultra-high frequency ultrasonography to improve the diagnosis of oral mucosal lesions, specifically focusing on oral squamous cell carcinoma. Current diagnosis relies on clinical exams and biopsies, but this study aims to assess how well this advanced imaging technique can visualize tissue beneath the mucosal surface to support clinical decisions. This approach may offer a minimally invasive, repeatable, and cost-effective diagnostic tool in oral medicine. The study involves using an ultrasonographic scan with a 70 MHz probe to examine oral soft tissue lesions. This device is designed to provide detailed images of the oral mucosa, potentially helping to measure tumor thickness and depth of invasion. Participants eligible for surgical treatment of oral squamous cell carcinoma will undergo this imaging as part of the study's evaluation process. Participants will be clinically diagnosed with oral squamous cell carcinoma and agree to be included in the study. Researchers will assess the depth of tumor invasion before surgery using the ultrasound scans. The study focuses on measuring the tumor invasion depth to better understand the role of this imaging method. Safety and participation are monitored throughout the study, but no additional treatments or follow-up periods are specified.

Researchers are studying the brain-to-brain connection between mothers and their infants born very preterm (VPT) compared to full-term (FT) infants. This study focuses on how early sensory stress and separation during Neonatal Intensive Care Unit (NICU) stays may affect neurodevelopment and parent-infant interaction. It aims to compare brain co-regulation patterns between FT and VPT mother-infant pairs and examine how an early parenting video-feedback (VF) intervention after hospital discharge might improve brain-to-brain synchrony in VPT dyads. The trial is a randomized controlled study with three groups: FT dyads, VPT dyads receiving the VF intervention, and VPT dyads receiving usual care. The VF intervention includes 8 weekly remote sessions over about two months after NICU discharge. These sessions help mothers understand and respond to their infants' behaviors through shared video feedback and guided play. The intervention focuses on sensory, behavioral, cognitive, and emotional aspects of parenting to support infant development and parent-infant closeness. Participants will complete questionnaires on maternal well-being, parenting stress, bonding, and infant development at 3, 6, and 9 months corrected age. At 9 months corrected age, mother-infant pairs will participate in a 5-minute EEG hyperscanning task to measure brain-to-brain co-regulation using Phase-Locking Value, Amplitude-Amplitude Coupling, and Imaginary Coherence. Researchers will analyze these brain synchrony indexes to understand their role in the effects of the VF intervention and to predict developmental outcomes.

Researchers are investigating a new treatment approach for metastatic colorectal cancer (mCRC) in patients whose tumors have MGMT silencing and are microsatellite stable (MSS). This approach combines several chemotherapy drugs, including fluoropyrimidines, irinotecan, temozolomide, and bevacizumab, aiming to overcome resistance seen with single chemotherapies. The study includes phase 1b and phase 2 parts, focusing on safety, dosing, and effectiveness of this combination in patients not previously treated for advanced disease. The treatment regimen starts with an induction phase of four 28-day cycles combining 5-fluorouracil, leucovorin, irinotecan, temozolomide, and bevacizumab (FLIRT-bevacizumab), followed by a maintenance phase where 5-FU/LV and bevacizumab are given every two weeks along with oral temozolomide on days 1 to 5 every 28 days. Doses of temozolomide are escalated during treatment to find the recommended phase 2 dose. Bevacizumab, irinotecan, leucovorin, and 5-fluorouracil are administered intravenously every two weeks. Participants undergo tumor assessments before treatment and every eight weeks to monitor disease progression, side effects, and treatment response. The study tracks safety by identifying dose-limiting toxicities during the dose-escalation phase and evaluates the treatment’s efficacy over 24 months. Patients continue treatment until disease progression, unacceptable toxicity, withdrawal, or death. The phase 1b portion has been completed, and the phase 2 part is ongoing.

Researchers are evaluating molnupiravir, a study medicine designed to stop the COVID-19 virus from multiplying, to see if it can prevent severe illness from COVID-19 more effectively than a placebo. This Phase 3 randomized, placebo-controlled, double-blind study focuses on non-hospitalized adults at high risk of severe disease progression due to COVID-19. The study addresses the need for alternative treatments for people who cannot take certain COVID-19 medications due to availability or potential drug interactions. Participants will receive either molnupiravir or a placebo, both given orally as two 400 mg film-coated tablets every 12 hours for 5 days, totaling 10 doses. Some participants may also receive remdesivir as part of standard care if clinically appropriate and available. The study compares the effects of molnupiravir with placebo in preventing severe illness outcomes. Throughout the study, participants will be monitored for outcomes such as hospitalization, death, or medically attended visits related to COVID-19 up to 29 days. Safety is assessed by tracking adverse events for up to about 5 months and discontinuation of study treatment due to adverse events for about 5 days. The study involves laboratory tests, symptom assessments, and safety evaluations to understand molnupiravir's impact on disease progression and participant health.

Researchers are investigating new treatments for people with high-risk, early-stage breast cancer, specifically targeting triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/HER2-negative breast cancer. These types have little or no HER2 protein and involve hormones like estrogen or progesterone. The study aims to evaluate if the addition of sacituzumab tirumotecan (sac-TMT), a targeted therapy, combined with pembrolizumab and chemotherapy can improve outcomes compared to pembrolizumab with chemotherapy alone. Participants receive treatments including sacituzumab tirumotecan, pembrolizumab, and chemotherapy drugs such as carboplatin and paclitaxel, all given by intravenous infusion. Rescue medications like antihistamines, acetaminophen, dexamethasone, or steroid mouthwash may be used as needed. The study is randomized and open-label, comparing sac-TMT followed by chemotherapy plus pembrolizumab to chemotherapy and pembrolizumab without sac-TMT. During the study, researchers will monitor participants up to about 30 weeks to assess the percentage of people with no remaining cancer cells at surgery. They will also follow participants for up to approximately 92 months to track event-free survival, meaning time without cancer growth, spread, or return. Participants will undergo imaging, clinical assessments, and laboratory tests to evaluate treatment effects and safety throughout the study.

Researchers are evaluating the efficacy and safety of rilvegostomig compared to pembrolizumab as first-line treatments for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have high PD-L1 expression. This Phase III, randomized, double-blind, and global study focuses on participants with stage IV mNSCLC who do not have certain genetic mutations or rearrangements and are eligible for systemic therapy. Participants receive either rilvegostomig or pembrolizumab intravenously on Day 1 of each 21-day cycle. The study compares these two biological treatments given as monotherapy. Both groups will be monitored over time to assess treatment impact and safety. Throughout the study, participants undergo evaluations including tumor measurements by CT or MRI, performance status assessments, and organ function tests. Researchers will measure overall survival and progression-free survival for up to approximately five years. Tumor samples are collected before treatment for central testing, and participants’ health and treatment responses are closely followed during the trial period.

Researchers are evaluating the long-term safety and tolerability of dazodalibep in adults with Sjögren's Syndrome. This phase 3 open-label extension study focuses on participants who have previously received dazodalibep or placebo in earlier phase 3 trials and completed those studies through Week 48. Participants will receive dazodalibep intravenously during this long-term extension study. The first dose is administered around Week 48 (+28 days) following the prior phase 3 studies. The study monitors safety and tolerability over an extended period to assess treatment-emergent adverse events up to 152 weeks. During the study, participants will undergo regular evaluations to monitor their health and any side effects. Researchers will collect data on adverse events that emerge during treatment. The overall goal is to gather long-term safety information to better understand how participants tolerate dazodalibep when used over an extended time frame.

Researchers are studying adults with confirmed Primary Biliary Cholangitis (PBC) and cirrhosis, a scarring of the liver caused by damage to bile ducts. PBC is a slowly progressing disease that causes bile acid buildup and further liver damage, which can lead to cirrhosis. This study aims to evaluate if elafibranor, a daily medication, can prevent worsening clinical outcomes such as the need for liver transplant or death, compared to a placebo. It also looks at the safety of long-term elafibranor use and its effect on symptoms like itching and tiredness. Participants will take either an 80 mg tablet of elafibranor or a matching placebo once daily for up to 3.5 years in a double-blind setup, meaning neither the participants nor researchers know who receives which treatment. This long-term treatment period is designed to monitor the drug's impact over time. The study includes two groups: one receiving elafibranor and the other receiving placebo, with treatment lasting up to approximately 42 months. During the study, participants will be regularly assessed from the start until 4 weeks after treatment ends, with a maximum involvement of 3.5 years. Researchers will measure event-free survival, tracking if participants avoid clinical events indicating disease worsening. Safety monitoring will include tracking side effects and overall health, while symptom impact will be evaluated. Participants will provide informed consent and follow the study protocol throughout this extended observation period.

Researchers are monitoring the long-term safety of efgartigimod, a biological treatment, in patients with generalized myasthenia gravis (gMG). This study is a non-interventional, prospective, post-authorization safety study designed to observe patients who are either starting or already receiving efgartigimod, as well as those with gMG who have not been treated with it. The study aims to compare the occurrence of serious infections and other safety outcomes over a period of up to 10 years. Patients with gMG who are expected to begin efgartigimod treatment at enrollment or who are currently in their first treatment cycle will be included in the efgartigimod group. Those with gMG who are not starting efgartigimod and have never received it will be enrolled in a non-efgartigimod group. There are no assigned treatments or interventions from the researchers; the study simply observes patients as they receive routine care. Participants will be followed for up to 10 years to track safety outcomes, including serious infections. Data collection will involve routine clinical assessments and monitoring as per standard medical practice. The study observes the real-world use of efgartigimod and its safety profile in managing gMG, providing valuable long-term information without altering patients' treatment plans.

Researchers are studying the effects of NEU-411 in men and women aged 40 to 80 years who have early Parkinson's Disease (PD) with increased activity in the LRRK2 pathway, identified through a genetic test. This Phase 2 trial aims to evaluate how well NEU-411 works and its safety in this specific group compared to a placebo. The study involves participants with clinically established or probable PD and focuses on those with LRRK2-driven PD. Participants will be randomly assigned to receive either NEU-411, a brain-penetrant oral drug that inhibits LRRK2 activity, or a matching placebo once daily for 52 weeks. After completing this treatment phase, participants will have a safety follow-up visit within two weeks. Those eligible may join an open-label extension to receive NEU-411 for an additional 26 weeks. During the study, researchers will monitor changes in a digital biomarker score using a Parkinson's Disease app from enrollment through 52 weeks, along with recording any treatment-emergent or serious adverse events until the study ends at 54 weeks. Assessments include genetic testing, clinical evaluations of PD status, safety monitoring, and tracking of side effects to understand the drug's effects and tolerability over time.