Orsay

Researchers are studying acute pyelonephritis (AP), a common bacterial kidney infection in children, focusing on those aged 1 month to less than 3 years without prior urological malformations. The study compares a short 3-day intravenous (IV) antibiotic treatment alone to a 3-day IV treatment followed by 7 days of oral antibiotics. The goal is to see if the shorter IV-only treatment is as effective at preventing infection recurrence and long-term kidney scarring, while possibly reducing antibiotic resistance and preserving gut microbiota diversity. Participants receive either IV ceftriaxone and/or amikacin once daily for 3 days, or the same 3-day IV treatment followed by 7 days of oral cotrimoxazole or cefixime. The study includes procedures like procalcitonin testing and fecal or rectal swabs collected at several points during and after treatment (day 0, 3, 10 or 17, and 31 or 38) to monitor bacterial presence and gut microbiota changes. Treatment begins after initial confirmation of infection and favorable early response. During the study, children are closely monitored for infection recurrence 28 days after completing antibiotics. Assessments include clinical evaluations, urine cultures, and monitoring for any adverse effects. The total participation covers treatment and follow-up periods to ensure safety and measure outcomes such as infection recurrence and bacterial resistance. This is a Phase 4 open-label randomized trial conducted across multiple centers.

Researchers are evaluating the effectiveness and safety of remibrutinib in adults aged 18 to 65 years with secondary progressive multiple sclerosis (SPMS). This Phase III study is randomized, double-blind, and placebo-controlled, designed to better understand how remibrutinib affects disability progression in SPMS patients over time. Participants will be randomly assigned to receive either oral remibrutinib tablets or matching placebo tablets during the Core Part of the study, which is event-driven and double-blinded. After this period, all participants may enter an Extension Part where they receive open-label remibrutinib treatment. This design allows researchers to compare remibrutinib against placebo and then monitor long-term effects when all participants receive the active drug. Throughout the study, participants will undergo regular assessments including MRI scans and clinical evaluations to track changes in disability using the Expanded Disability Status Scale (EDSS). The primary outcome measured is the time to confirmed disability progression over six months, with follow-up lasting up to approximately five years. Safety, tolerability, and other health parameters will also be closely monitored during both study phases.

Researchers are investigating liver diseases by assessing the reproducibility of liver stiffness measurements (LSM) using FibroScan examinations with a single probe compared to standard reference probes (M and XL). This international, prospective, interventional study will include 309 adult patients across sites in Hong Kong and France. The purpose is to explore whether a single probe FibroScan can provide consistent liver stiffness results comparable to the established reference probes. Participants will undergo a series of FibroScan examinations using different probes. For the first 50 patients, three exams will be performed with three different single probes followed by an exam with the reference FibroScan probe, with the order of the single probes alternated to reduce bias. For patients 51 to 309, two exams will be done: one with the single probe FibroScan and one with the reference FibroScan, with the order of exams alternated. All exams are conducted at the same measurement points to ensure accuracy. During the study, researchers will compare liver stiffness measurements from the single probe FibroScan to those from the standard reference probes on the day of examination. Participants will be monitored for their ability to complete the exams, and results will help evaluate the reliability of the single probe FibroScan device. The total involvement includes these same-day assessments, with no long-term follow-up detailed in the study information provided.

This research aims to develop a new method for measuring liver stiffness using FibroScan in adults with liver diseases. Conducted as a European, prospective, interventional, multicenter clinical investigation, the study will include 114 adult patients from two French medical centers. It focuses on patients with liver disease, suspected liver disease, or related consequences from any cause. Participants will undergo multiple FibroScan examinations using both a Research FibroScan device and a Reference FibroScan device. The examinations are structured in phases: Patients 1 to 25 will have two exams comparing the Research and Reference devices at the same measurement point. Patients 26 to 75 will have alternating exams between the two devices. Patients 76 to 114 will receive four consecutive exams split between the Research and Reference devices, all performed at the same measurement points using the same probes. During the 24 months of the study, researchers will assess the consistency and precision of liver stiffness measurements using the new method compared to the standard one. Participants' involvement includes multiple examinations, with measurements carefully recorded to evaluate reduced variability within single examinations. Safety and study adherence will be monitored throughout the study period.

Major depressive disorder is a leading cause of disability worldwide, with commonly used antidepressant medications often having limited effectiveness and a delayed onset of 2 to 6 weeks. This delay can necessitate hospitalization, especially for those experiencing severe major depressive episodes (MDE). Researchers are investigating whether adding intravenous ketamine to venlafaxine treatment can improve early symptom relief in hospitalized patients with severe unipolar depression. Previous studies have shown ketamine's benefits in treatment-resistant depression and its potential to increase synaptic density in the brain. In this Phase 3 study, participants are randomly assigned to receive either intravenous ketamine or a placebo alongside venlafaxine over one week, with infusions occurring on Days 1, 4, and 7. Both groups continue venlafaxine treatment while receiving their assigned intravenous infusions. This design aims to assess the early effects of ketamine compared to placebo when used with venlafaxine in treating severe depressive episodes. Participants will be closely monitored through clinical assessments of depressive symptoms at the start of the study and after one week. Researchers will measure changes in depressive symptomatology to evaluate early treatment efficacy. Safety monitoring and follow-up will also be conducted throughout the study period. Overall participation lasts at least one week during which treatment and assessments are performed to determine the early impact of the interventions.

Researchers are investigating early psychosis, including schizophrenia, as a progressive disorder where cognitive problems appear before symptoms start. The study evaluates a new approach called Composite Personalised Care (CPC) that combines cognitive training and tailored neuroprotective treatments to improve functional recovery in young people at ultra-high risk or experiencing their first episode of psychosis. This approach aims to support brain plasticity and target biological factors like inflammation and nutritional deficiencies that may contribute to psychosis onset. The study compares three interventions over 12 weeks: digital cognitive training using the PSYCARE application, with an optional virtual reality cognitive remediation for those with higher cognitive deficits; personalized neuroprotective supplements including vitamin B12, folinic acid, Omega 3 fatty acids, and N-acetyl-cysteine, adjusted to each participant's biological profile; and treatment as usual, which includes standard psychoeducation and group cognitive behavioral therapy, plus antipsychotics for first-episode psychosis patients. The personalized supplements are given daily for 12 weeks. Participants aged 15 to 30 years will be involved in cognitive training and receive personalized care tailored to their needs. Researchers will assess global functioning 3 to 4 months after starting the interventions to measure improvements. The study also monitors biological and cognitive factors that might affect outcomes. This trial offers remote, youth-friendly tools and aims to improve early intervention strategies for psychosis by enhancing cognitive abilities and functional recovery.

Spirometry is a widely used, non-invasive test that measures lung function by recording forced breaths to determine forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). It helps detect and characterize respiratory diseases and assess treatments but only provides global lung ventilation information and requires active patient cooperation. This study aims to evaluate a new technique called 3D magnetic resonance spirometry, which creates detailed local maps of lung function and mechanical behavior to improve diagnosis of regional lung diseases in healthy individuals and patients with asthma, COPD, or lung transplants. Participants will undergo standard spirometry tests in sitting and lying positions with different breathing types, as well as dynamic 3D lung MRI scans in prone and supine positions before and after a bronchodilator (salbutamol) test. The salbutamol is given via inhalation at a total dose of 400 mcg. The study compares the results from traditional spirometry with those from the 3D MRI spirometry to assess agreement and differences across various lung regions. During the study, participants will be evaluated through lung function tests and dynamic MRI imaging at different positions and before and after medication. Researchers will measure correlations and differences in expiratory volumes and tidal volumes between lung sides and lung regions over two months. The study involves detailed lung function assessments to better understand local lung mechanics and respiratory health in various patient groups and healthy volunteers.

Researchers are investigating the neural mechanisms behind different forms of Alzheimer's disease, focusing on patients with early onset symptoms under 65 years old and those with a focal brain condition called posterior cortical atrophy (PCA). The study aims to understand why some patients show widespread cognitive deficits while others have more localized brain damage despite having similar pathological features like amyloid and tau protein deposits. The goal is to uncover how certain brain networks may resist damage, a phenomenon called resilience, which could influence future treatments and rehabilitation strategies for Alzheimer's disease. Participants will undergo a combined PET and MRI scan using a hybrid camera to assess brain function and structure. This includes a 30-minute PET scan performed 80 minutes after an injection of a radioactive tracer, followed by various MRI sequences such as anatomical, diffusion, and functional imaging. The entire imaging session lasts about three hours and is designed to capture detailed information about brain network changes and protein deposits related to Alzheimer's and PCA. During the study, researchers will collect data on brain network resilience and the extent of brain damage over a three-month period. Assessments include neuropsychological evaluations, imaging scans, and laboratory tests to confirm Alzheimer's pathology. The study also monitors participant safety through blood tests and checks for any medical conditions that might affect results. Findings from this research could help refine diagnosis, tailor treatments, and improve understanding of resilience mechanisms in neurodegenerative diseases.

The CLOSE trial (NCT00562289, NEJM 2017) has unambiguously demonstrated the superiority of patent foramen ovale (PFO) closure over antiplatelet therapy alone in patients aged up to 60 years with a PFO associated with an atrial septal aneurysm (ASA) or a large right-to-left shunt (so-called "high-risk PFO"), and an otherwise unexplained ischemic stroke. Oral anticoagulant therapy is also a logical approach assuming that PFO-related strokes are due to paradoxical embolism which implies a venous source of embolism, or to direct embolization of a thrombus formed at the atrial level. The CLOSE trial also suggested that oral anticoagulants might reduce stroke recurrence compared to aspirin. There is accumulating evidence that presence of a PFO is significantly associated with cryptogenic stroke in patients over 60 years. Cryptogenic ischemic strokes represent about one third of all ischemic strokes in patients older than 60 years. However, the optimal therapeutic strategy in patients older than 60 years with a PFO and an otherwise unexplained ischemic stroke is unknown, because these patients were excluded from randomized trials. The hypothesis tested in this trial is that transcatheter PFO closure plus long-term antiplatelet therapy is superior to antiplatelet therapy alone and that oral anticoagulant therapy is superior to antiplatelet therapy to prevent recurrent stroke in patients aged 60 to 80 years who have a high-risk PFO and a recent otherwise unexplained ischemic stroke.

Researchers are investigating treatments for advanced metastatic adenocarcinoma of the stomach and gastro-esophageal junction, a serious cancer with low survival rates. Current treatments include chemotherapy combinations and immunotherapy, which have improved outcomes for some patients. However, when cancer progresses after these therapies, options are limited, and new approaches are needed to extend survival and maintain quality of life. This international Phase III trial (FRUQUITAS) tests whether adding fruquintinib, an anti-angiogenic drug, to the oral chemotherapy drug trifluridine/tipiracil can improve survival for patients whose cancer has continued to grow despite prior treatments. The study compares two groups: one receiving trifluridine/tipiracil alone and the other receiving trifluridine/tipiracil combined with fruquintinib. Trifluridine/tipiracil is given orally twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle, repeated until disease progression or unacceptable side effects. Fruquintinib is taken orally once daily for 21 days of a 28-day cycle, also continued until progression or toxicity. This combination aims to block the tumor's blood supply while providing chemotherapy. The trial evaluates if this approach extends overall survival compared to chemotherapy alone. Participants will be adults with metastatic adenocarcinoma who have received two or three previous treatment lines. They will undergo regular assessments including tumor evaluations per RECIST criteria, blood tests to monitor organ function, and safety checks. Researchers will measure overall survival up to 18 months after starting treatment. The study involves ongoing monitoring for side effects and treatment tolerance, with participation lasting until disease progression, unacceptable toxicity, or withdrawal. Biological samples may also be collected for further research, and informed consent is required before enrollment.