Clinical trials

This is a pivotal study designed to demonstrate the non-inferiority of the Odon Device™ versus vacuum extraction

The study is sponsored by the University Hospital of Besancon under the coordination of Dr. Julie Castagna from the Department of Dermatology and Allergology. Approximately ten percent of patients with severe chronic urticaria remain refractory to standard or optimized biologic therapy, and this observational multicenter retrospective project aims to thoroughly evaluate these challenging cases. By analyzing a target population of seventy adult participants across French hospitals, the research focuses on identifying specific clinical and biological traits, outlining risk factors associated with non-response to high-dose treatment regimens, and documenting the alternative therapeutic strategies that follow treatment failure. Data collection is structured retrospectively to cover the period from January 2020 through the end of December 2026, leveraging existing medical records without imposing any additional clinical visits or physical procedures on participants, aside from sending an informational mailer to ensure transparency regarding data utilization. Eligibility requires documented resistance to optimized omalizumab defined by a validated Urticaria Control Test score below six or less than fifty percent clinical improvement as judged by the investigator, alongside mandatory affiliation with the French social security scheme and a lack of objection from the participant regarding the secondary use of their personal health information. Strictly enforced exclusion conditions eliminate cases where omalizumab was initiated for alternative diagnoses, halted due to adverse side effects, or administered to vulnerable groups such as pregnant individuals, minors, or those under legal protection frameworks. To maintain absolute data integrity and regulatory compliance, individual participant data will not be shared publicly or externally because the documentation contains confidential and fully anonymized clinical details designed strictly to safeguard patient privacy throughout the research lifecycle.

Acute hypoxemic respiratory failure (AHRF) is a common condition associated with substantial morbidity, mortality, and healthcare resource utilization. Although advances in oxygen therapy, particularly high-flow nasal oxygen (HFNO), have improved the management of AHRF, the transition from HFNO to conventional low-flow oxygen therapy remains an important and understudied phase of patient care. During oxygen weaning, oxygen flow is usually adjusted manually by healthcare professionals according to a target oxygen saturation (SpO₂). Because oxygen saturation is often assessed intermittently outside continuously monitored settings, patients may experience episodes of hypoxemia or hyperoxia before oxygen flow is adjusted. FreeO2 is an automated oxygen titration system that continuously adjusts oxygen flow according to the patient's SpO₂. Its safety and effectiveness have been demonstrated in several clinical settings, but its use during oxygen weaning after HFNO has not been specifically evaluated. The objective of this study is to assess whether the use of the FreeO2 system during oxygen weaning after HFNO in patients recovering from acute hypoxemic respiratory failure improves oxygen saturation control and facilitates the weaning process compared with standard oxygen therapy.

Several cancer immunotherapies that target the PD-L1/PD-1 pathway (i.e., checkpoint inhibitors) show promising clinical activity in patients with HCC. In particular, atezolizumab selectively targets PD-L1 to prevent interaction with receptors PD-1 and B7-1, thus reversing T-cell suppression. Moreover, atezolizumab in combination with bevacizumab, a monoclonal antibody that targets VEGF and inhibits angiogenesis, is associated with an objective response rate of 27.3% (Cheng et al. 2021; Finn et al. 2020). This tumor response has led to FDA (Food and Drug Administration) and EMA (European Medicines Agency) approvals, in first-line treatment in unresectable HCC. Combinations studies evaluating anti-CTLA4 and anti-PD1/PDL1 antibodies displayed greater benefits (Abou-Alfa et al. 2022). In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, a single priming dose of tremelimumab (anti-CTLA-4) plus durvalumab (anti-PD-L1) in the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen significantly improved OS versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. In the HIMALAYA study, STRIDE regimen induced long term survival (defined as the absence of progression above 36 months following inclusion) in 103 out of the 393 patients exposed to this strategy (26%). The identification of biomarkers allowing the prediction of immunotherapy efficacy in HCC is still an unmet medical need.

The primary objective of the SLEEPLAY study is to assess the feasibility of a research protocol investigating the impact of video games on sleep in adults. More specifically, this study aims to identify potential barriers, facilitators of participation, and participant adherence to various measurement tools (such as actigraphy and melatonin assays) to validate the protocol for a larger future study. Additionally, it seeks to optimize the recruitment of regular adult gamers and determine the conditions that will enable better collection of objective sleep data. The relevance of this feasibility study lies in its ability to test and refine the methodology, thereby facilitating future research while minimizing costs and implementation time.

The aim of this multicenter prospective interventional pilot study is to describe the evolution of myocardial fibrosis in cirrhotic patients before and after liver transplantation (LT). Through multimodal analysis of myocardial function and architecture, and analysis of specific markers of inflammation, we aim to explore the following hypotheses: 1) systemic inflammation promotes myocardial fibrosis in cirrhotic patients and could be an early marker of cirrhotic cardiomyopathy; 2) LT allows resolution of myocardial fibrosis by preventing the bacterial translocation that favors the development of deleterious systemic inflammation.

This study aims to describe, over a one-year period, the clinical, biological, and histological evolution of a cohort of kidney transplant recipients who developed antibody-mediated rejection and were treated with extracorporeal photopheresis.

Recent advances in personalized 3D modeling make it possible to consider personalized hand modeling based on cone-beam CT. The goal is to develop a personalized 3D modeling tool for use in routine clinical practice that reduces both the radiation dose to which patients are currently exposed during CT scans and the time required to process CT data (segmentation). the main, objective of the study is to compare the quality of 3D hand modeling based on cone-beam CT with the gold standard of computed tomography. This prospective, single-center, interventional study will include 6 healthy volunteers.

In the present TACTIC clinical trial, the investigators propose to determine the clinical interest and immunological efficacy of a treatment combining MP0317 the FAP (Fibroblast Activation Protein)-dependent CD40 agonist, with anti-PD-L1(Programmed Death-Ligand 1) therapy (durvalumab) and gemcitabine-cisplatin-based chemotherapy in unresectable cholangiocarcinoma. The main objective is to assess the 12-month progression free survival (PFS) rate in the experimental arm. The trial proposed is a non-comparative proof of concept randomized two-stage phase II. The control arm will serve to verify the good calibration of the null hypothesis made in the experimental arm and to provide "true" controls for translational investigations. A semi-continuous monitoring of toxicity is planned in the experimental arm during the first stage of the study to warrant the tolerability of the experimental treatment and then to guarantee the security of the patients. 75 patients (50 in the experimental arm) will be included. The investigators will also decipher, as a translational objective, the molecular and immunological parameters determining the clinical outcomes.

Despite technological advances, a genetic etiology has been identified in only about 50% to 60% of patients with Neurodevelopmental disorders (NDDs), with a higher diagnostic yield in the syndromic NDD and IDD subgroups. However, identifying a precise etiological diagnosis is essential to optimize patient care, clarify their prognosis, consider targeted therapies, refer families to appropriate resources and support, and provide genetic counseling to relatives. The tests typically offered as part of the etiological assessment of syndromic NDDs and IDD include DNA microarray analysis, testing for fragile X syndrome and genome sequencing from a blood sample. When this assessment remains negative, the cause usually remains unknown. Mosaic genomic abnormalities (or post-zygotic variations) are a common cause of negative results in current diagnostic genetic tests and represent a field of research that has yet to be fully explored outside of skin disorders. Identifying mosaic genomic abnormalities remains technically complex due to the difficulty of detecting low levels of mosaicism and limited access to the tissue of interest when the variation is absent from blood tissue. High-depth exome sequencing is the technique of choice for detecting low levels of mosaicism. In the case of NNDs, as the affected tissue is not available, the buccal epithelium is an interesting alternative to blood, as it is easily accessible and inexpensive. The objective of our study is to evaluate the diagnostic yield of high-depth exome sequencing technology on a DNA extracted from a buccal swab in the etiological assessment of patients with IDD or syndromic NDD whose reference analysis (genome sequencing on blood) proved inconclusive.

The challenge for medical oncology is to develop plasma biomarkers that can detect the influence of the stroma on diagnosis, prognosis and response to chemotherapy. Today, there is no validated blood test to help diagnose pancreatic cancer (PDAC). The search for blood biomarkers of the tumor stroma and immunological markers is therefore a major challenge in orienting the diagnosis towards PDAC and optimizing the therapeutic management of pancreatic cancers. The aim of the study is to identify biomarkers associated with the presence of malignant pancreatic lesions (patients from the Pancreas-CGE cohort, a cohort already set up by our team) compared with benign lesions (patients followed up for benign pancreatic lesions). Candidate biomarkers from our preliminary work will be considered initially. Other biomarkers may be explored secondarily. The ultimate goal is to develop a clinico-biological signature that is as efficient as possible in predicting the presence of malignant pancreatic lesions compared with benign ones.

The TERTIO trial will propose to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with anti-PD-L1 therapy (atezolizumab) and bevacizumab in unresectable HCC by evaluation of the objective response rate at 6 months (randomized phase II, 10 centers, 105 patients)

Colorectal cancer (CRC) is the third most common cancer in men and the second in women with an incidence of 43,350 new cases in 2018. This incidence is increasing every year. Early detection is crucial in this pathology. In France, free screening is organized by health insurance for people aged 50 to 74 years. This screening is based on an immunological test (FIT: Fecal Immunological test), which aims to detect the presence of blood in the stool. In fact, some polyps or cancers cause bleeding that is often minimal and therefore difficult or even impossible to detect with the naked eye. If this test is positive, a colonoscopy is done to check whether or not abnormalities are present in the colon or rectum. Performed under anesthesia, this examination can detect the possible presence of polyps or cancer. Recently, with the covid-19 epidemic, the investigators were faced with an extension of the delays for colonoscopies which led to delays in patient care. To prevent this, they propose to develop a blood test that would allow rapid identification of patients with colorectal cancer, requiring rapid management. This blood test will permit to have a parameter for stratifying the therapeutic care in the event of epidemia or situation that constrains the organisation of the health system.

The goal of this retrospective observational study is to evaluate the diagnostic performance of the AORTAs score integrated with environmental exposure data (AORTAs-E) for the identification of Acute Aortic Syndrome (AAS) during initial maangement in the emergency departement. The main question it aims to answer is: Can the integration of real-time meteorological and atmospheric pollution data improve the early identification of AAS in patients presenting in the emergency department for chest, abdominal, or back pain? Researchers will analyze medical records and environmental data for 580 adult patients (290 cases with confirmed AAS and 290 controls) managed at the University Hospital of Besançon between 2014 and 2026. Environmental exposure, including temperature and pollutant concentrations, will be calculated based on each patient's residential address to determine if adding these factors to clinical data increases diagnostic accuracy.

Shock is a common and serious cause of admission to intensive care. Vascular filling is one of the cornerstones of shock treatment, aimed at increasing cardiac output and restoring adequate organ perfusion through rapid intravenous administration of a solution. However, this vascular filling can be accompanied by venous congestion, which can be harmful. Fluid administration must therefore be sparing and carefully considered. However, it is difficult to assess the correct amount of intravenous fluid to inject. Multi-site venous ultrasound (inferior vena cava, suprahepatic vein, portal vein, renal vein), recently published under a score called VExUS, could be a useful bedside tool for documenting venous congestion and avoiding excessive vascular filling. Nevertheless, this tool has been little evaluated in the general intensive care population, particularly in patients with acute respiratory distress syndrome (ARDS). Its link with other venous sites (femoral, popliteal) has also been little studied to date. The main objective of our study is to describe the distribution of the VEXUS score among patients in a general intensive care unit. The secondary objectives are: * To study the feasibility of measuring the VEXUS score in patients with ARDS, including during prone positioning, a recommended and frequently used treatment for this condition, which could make it difficult to acquire venous ultrasound data. * In this case, other more accessible venous flows could be analysed, namely the femoral venous flow and the popliteal venous flow. We will therefore also study their feasibility during prone positioning sessions. * Subsequently, we will study the correspondence between the VEXUS score and these other types of venous flow (femoral, popliteal). * Finally, we will evaluate the association between the VEXUS score in our general intensive care population and the long-term prognosis of patients, in this case death on day 28 and the occurrence of acute renal failure requiring renal replacement therapy during the intensive care stay.

APhyDeM is a randomized controlled study investigating the relationship between adapted physical activity and mitochondrial function in postmenopausal women with major depressive disorder. Depression is associated with metabolic dysfunction, including alterations in mitochondrial activity and inflammatory processes. Physical activity has been shown to influence mitochondrial function, yet individuals with depression frequently experience reduced physical activity levels. This study aims to evaluate whether an adapted physical activity program can improve mitochondrial function compared with a control intervention. Mitochondrial function will be indirectly assessed using near-infrared spectroscopy to measure post-exercise muscle oxygen recovery kinetics. The study compares adapted physical activity with a non-physical therapeutic intervention in postmenopausal women receiving care in a psychiatric day hospital setting.

This feasibility study aims to assess interest, recruitment, and adherence to a supervised physical activity (APA) program among individuals with Alcohol Use Disorder (AUD). It also investigates the program's impact on sleep quality and efficiency. Key objectives include evaluating recruitment feasibility, assessing randomization acceptance, quantifying adherence rates, and identifying sensitive sleep assessment tools. The study will explore whether APA improves sleep outcomes in AUD patients with sleep complaints, laying groundwork for larger-scale research. Participants will engage in APA sessions, complete sleep assessments (including sleep diaries and psychometric scales), and provide sociodemographic data and past activity adherence.

Background: SGLT2 inhibitors reduce CHF morbidity/mortality but are underutilized in elderly patients with acute decompensated CHF (ADCHF) admitted outside cardiology departments. Objective: Assess feasibility of early ED-initiated gliflozin therapy in elderly ADCHF patients. Design: Multicenter, randomized, open-label pilot study; N=144 patients (72 per arm) across 6 EDs over 30 months. Population: Age ≥75 years, ED admission for ADCHF (symptomatic worsening, congestion, elevated natriuretic peptides), gliflozin-naïve, requiring hospitalization. Key Exclusions: Type 1 diabetes, eGFR \<25 mL/min/1.73m², cardiogenic shock, recent ACS, cardiology ward admission. Intervention: Treatment: Dapagliflozin 10mg daily within 24h + cardiac nurse telephone follow-up at 1 month Control: Standard care only Primary Outcome: Feasibility (organizational implementation, acceptability, protocol adherence, timeline compliance). Follow-up: 7-day visit (clinical assessment, NT-proBNP, echocardiography) and 3-month cardiology consultation (mortality, rehospitalization, QoL, biomarkers, safety parameters).

Glioblastomas (GBM) are the most frequent brain tumors and one of the most lethal adult cancers despite maximal multimodal therapy. Despite maximal safe resection followed by radiotherapy and temozolomide (TMZ) ± tumor-treating fields, median overall survival for newly diagnosed GBM remains around 18 months and long-term survival is rare, and recurrence is nearly universal. So, the development of new therapeutic strategies is a critical unmet need in GBM. Despite the limited success of anti-PD(L)-1 therapy, immunotherapy remains a promising option in GBM. Current challenge supports to develop combinatorial therapy approaches considering the particular immune tumor microenvironment in GBM. Anticancer vaccines have shown promising signs of efficacy in GBM but critical factors challenge their efficacy. CD4 T help is of major interest for cancer vaccine effectiveness and for immune checkpoint inhibitors success. We previously designed UCPVax a CD4 T helper-targeted cancer vaccine derived from telomerase (TERT), a very attractive GBM-associated antigen (Adotévi O, J Clin Oncol 2023 ; Laheurte C, Cell Report Med 2025). The induction of robust tumor reactive CD4 T cell response with UCPVax together with TMZ-mediated immune effects will promote recruitment of effectors immune cells into tumor bed creating a more suitable microenvironment for anti-PD-1 action. This is a proof-of-concept phase II trial to evaluate the efficacy of maintenance therapy evaluating UCPVax +/- pembrolizumab combined to standard treatment in newly diagnosed unmethylated MGMT glioblastoma. A translational research network will be implemented to better understand the therapeutic efficacy of this combination.

This study will assess the diagnostic contribution of early abdominal ultrasound for acute abdomen in premature newborns. Early ultrasound assessment would provide diagnostic assistance, in conjunction with clinical examination and biological testing, in the three main clinical situations encountered with an acute abdomen in premature infants: enterocolitis (digestive translocation of a bacterium secondary to inflammation, local fragility of the digestive tract, associated ischemic phenomena), reflex ileus (decrease in intestinal peristalsis secondary to peritoneal reactivity following inflammatory phenomena) and digestive immaturity (expressed by bloating, regurgitation, absence of spontaneous transit, related to the degree of prematurity).

Fluoropyrimidine drugs (5-Fluorouracil or 5-FU and its prodrug capecitabine) are a widely used in the treatment of numerous solid tumors in adults. Approximately 85% of administered 5-FU is rapidly catabolized in the liver into inactive dihydrofluorouracil (5-FUH2) by dihydro-pyrimidine dehydrogenase (DPD), leaving only a small fraction of the initial drug for an eventual transformation into cytotoxic metabolites. Impeded DPD activity is associated to an increase of cytotoxic metabolites leading to potentially very severe toxicities. To prevent these toxicities, a pre-therapeutic measurement of plasma uracil can help assess DPD activity. Indeed, uracil is an endogenous substrate of DPD and an increase in its plasma concentration may be associated with a decrease in DPD activity. In this case, a reduction of the fluoropyrimidine dose is suggested. However, the investigators observed that uracilemia increased concomitantly to the severity of renal impairment. There are two possible explanations for this observation. Either the renal impairment reduces the renal elimination of uracil from blood, or DPD activity is actually impaired. In both cases, this can explain an increase in plasma uracil concentration. However, the impact on fluoropyrimidine dosage is different in the two cases. If the increase in uracilemia is due to renal impairment, DPD activity remains unaffected and there is no need to reduce the fluoropyrimidine dose. If DPD activity is actually impaired, a reduction in the fluoropyrimidine dose is required. In cases of renal impairment, uracilemia may therefore not be as relevant for DPD assessment as in the absence of renal impairment. To assess if DPD activity is actually impede during renal impairment, the DPD activity of Peripheral Blood Mononuclear Cells (PBMCs) will be assessed together with uracilemia in patients with or without renal impairment. As uracilemia decreases after dialysis, the DPD activity of Peripheral Blood Mononuclear Cells (PBMCs) will also be assessed in patient before and after dialysis. Four groups of 50 patients will be studied: patients with normal renal function with hyperuracilemia (uracilemia ≥ 16 ng/mL) or normal uracilemia (uracilemia \< 16 ng/mL) ; and patients with renal impairment with hyperuracilemia (uracilemia ≥ 16 ng/mL) or normal uracilemia (uracilemia \< 16 ng/mL). The main objective of the study is to describe the distribution of DPD activity in these four populations. The secondary objectives are to determine in normorenal patients the optimal threshold for DPD activity in non-deficient patients, allowing differentiation between deficient and non-deficient patients based on uracilemia ; and to describe in patients with impaired renal function the distribution of uracilemia with respect to the threshold previously described with the aim of verifying the relevance of uracilemia as a marker of DPD activity in such patients.

Ten years after our team's publication, practices have changed considerably in the management of severe cirrhotic patients. This study will analyse these practices in primary care hospitals and in a tertiary centre, and assess the impact of these changes on the prognosis of these patients. The following hypotheses will be tested: * Improvement in intensive care and overall prognosis compared with data from the literature prior to 2014 * Improved access to liver transplantation compared with the literature prior to 2014 * Improvement in intensive care unit practices (for example: application of recommendations published by learned societies concerning the intensive care unit management of patients with cirrhosis, access to comfort care, degree of clinical severity on admission to the intensive care unit, etc.). * Centre' effect: variability in the phenotype of patients admitted to intensive care depending on the technical facilities available and whether or not the hospital centre has access to TH.

Context: Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) is a rapid-onset, sensorineural hearing loss of unknown etiology. It is one of the most common ENT emergencies, with spontaneous recovery occurring in 32% to 65% of cases. Treatment remains controversial, and the need for treatment itself is debated. Oral corticosteroids (OCS) are commonly used as first-line therapy, although they may have short-term side effects. Intratympanic corticosteroid injections (ITCIs) are an option for patients with contraindications to OCS or as a salvage treatment. The most recent Cochrane review includes three placebo-controlled studies on OCS efficacy (totaling 267 patients): two found no superiority of OCS, while one showed improvement in hearing. These studies are inconsistent and present methodological biases. Therefore, a sufficiently powered study is needed to assess OCS efficacy and establish clear treatment recommendations for ISSHL. Objectives: Primary Objective: To demonstrate the equivalence of OCS as first-line treatment for ISSHL compared to no treatment, in terms of hearing recovery between days 7 and 10. Secondary Objectives: To assess the effect of OCS versus no treatment on tinnitus, and hearing recovery based on initial severity of ISSHL. To evaluate hearing recovery in patients treated with rescue ITCIs. In the absence of equivalence, to investigate the superiority of OCS over no treatment. Methods: This multicenter, randomized, controlled equivalence trial will include two arms, each with 215 patients: one receiving OCS and the other a no-treatment control. In the absence of early hearing improvement, ITCIs will be administered regardless of study arm. Perspective: The goal is to clarify the role of OCS in treating ISSHL and guide the development of updated treatment recommendations.

The goal of this exploratory, interventional, multicentre study is to compare the prefrontal activity during a negative emotion regulation task in women with Binge-Eating Disorder (BED) and healthy women with and without Emotional Eating (EE). The aim of this study is to compare the prefrontal processing of cognitive control of emotions between BED and EE and to compare the emotional processing and emotional experience between BED and EE. The study will thus compare four experimental groups: patients with BED, BMI-matched healthy volunteers with EE, BMI-matched healthy volunteers, and healthy volunteers of normal weight without BED. Participants will perform a down-regulation task of negative emotions elicited by negative pictures. During this task, their cerebral activity will be recorded using functional near-infrared spectroscopy (fNIRS), as well as their autonomous activity (skin conductance, pulse rate, respiration rate).

The aim of this study is to validate a new hybrid (ecological + virtual) decision-making tool. The difference in behavior (risky choices) between the "hybrid" task and the "virtual" task will be evaluated.