Clinical trials

The purpose of this study is to evaluate the safety and efficacy of FOXP3-T4 (an autologous gene therapy) alone or in combination with low-dose IL-2 for the treatment of IPEX syndrome. The therapy involves the transplantation of autologous CD4+ T-cells transduced ex vivo with the LV-EF1a-FOXP3-LNGFR lentiviral vector. The study follows a staggered approach: the first two patients will receive FOXP3-T4 monotherapy. Subsequent patients will receive FOXP3-T4 followed if needed by low-dose IL-2 treatment consisting of a daily dose for 5 days, then weekly administrations for 3 months. The study aims to stabilize autoimmune manifestations and potentially cure the underlying disease, ultimately allowing for the discontinuation of ongoing immunosuppressive treatments.

In orthoptics, fusional vergence (FV) measurement is one of the key tests used to assess fusion ability. These amplitudes are generally reduced in individuals with convergence insufficiency. Fusional vergence are quantified by placing a prism bar randomly in front of one eye-first for distance vision and then for near vision. Rehabilitation exercises using the prism bar are also performed in the same manner. Depending on orthoptic practice, the prism bar is placed in front of the left eye or the right eye, in a dogmatic manner, or in front of the right eye, in a conventional manner, without any study providing any justification. However, some practitioners report interocular differences when measuring fusion amplitudes depending on which eye is prismed, while others do not. The hypothesis put forward is that, in individuals with an interocular difference in fusional vergence, ocular dominance (sensory and motor) could be the cause of this measurement discrepancy. The objective is therefore to compare the difference in fusional vergence depending on whether the dominant or non-dominant eye is tested, using a randomized order of eyes and tests. If this hypothesis is confirmed (greater fusional vergence when tested on the dominant eye), this would: (1) enhance our understanding of fusion mechanisms, (2) provide more targeted insights for the assessment, quantification, and rehabilitation of fusional vergence to improve the effectiveness of orthoptic intervention.

In patients with septic shock, vasopressin is increasingly used in combination with norepinephrine, but its timing of initiation remains heterogeneous and its clinical hemodynamic effects are still insufficiently characterized. Available data suggest variable responses, which may depend on the hemodynamic phenotype at the time of treatment initiation. In particular, the effects of vasopressin may differ according to the presence of preload dependency, baseline cardiac output, impaired systolic function, or baseline diastolic arterial pressure, reflecting the degree of vasoplegia. In this context, the VASO-PHENO study aims to provide a detailed and dynamic description of the early hemodynamic and clinical effects of vasopressin initiation in septic shock. To date, no clinical study has systematically and dynamically evaluated the effects of vasopressin on central and peripheral hemodynamic parameters according to the hemodynamic profile at the time of its initiation. Describing these effects appears essential to better understand the variability in clinical responses and to contribute to a more rational and personalized approach to vasopressor escalation in septic shock.

This study evaluates adherence to a personalized prevention plan in female night shift workers at increased risk of breast cancer. Night shift work is associated with circadian disruption and increased cancer risk, as well as cardiovascular and reproductive health risks. Participants attend an initial consultation including clinical assessment and development of a personalized prevention plan targeting modifiable risk factors such as alcohol consumption, physical activity, smoking, diet, and weight. Follow-up is conducted remotely over 5 years to assess adherence to recommendations and screening. Participant satisfaction and adherence to additional consultations are also evaluated.

The purpose of this study is to evaluate treatment adherence among patients followed in the Department of Inherited Metabolic Diseases at Necker Hospital, in order to assess the need for implementing a therapeutic education workshop focused on medication adherence.

It is proposed to conduct an exploratory study to analyze the skin, intestinal, and salivary microbiome, as well as the skin mycobiome and virome, of patients (adolescents and young adults) with Netherton syndrome, a condition characterized by an impaired skin barrier that most likely promotes the development of allergic manifestations. The study will be conducted on patients with Netherton syndrome and control subjects in order to investigate possible correlation factors between the three microbiomes and identify which ones.

Acute respiratory distress syndrome (ARDS) in children is associated with significant morbidity and mortality. Current studies seek to individualize the management of children by defining several phenotypes, based until now mainly on clinical presentation. A better understanding of the respiratory mechanics of each patient could allow the individualization of other phenotypes and adapt their management with individualized ventilation. The method for detecting airway opening pressure (AOP) in children has not yet been validated and the reference methods in adults are difficult to apply in children due to their physiological particularities. The main objective of the study is to evaluate the feasibility of two methods for measuring airway opening pressure in invasively ventilated pediatric patients.

The project is to explore in humans the hypothesis of the link between the alteration of tubulo-interstitial metabolism and the rate of deterioration of renal function by comparing various nephropathies.

The primary objective in this study is to achieve a 15% 6-month improvement in therapeutic adherence among patients with chronic pathologies, thanks to a simple, standardized and redundant message delivered by healthcare professionals during consultations/interviews Trained healthcare professionals deliver a simple, standardized and redundant 3-point message to patients, based on the levers of action concerning therapeutic adherence. This message is delivered with the aim of modifying the patient's behavior with regard to treatment intake.

The purpose of this study is to identify and analyze suboptimal perinatal (obstetric-pediatric) care in the occurrence and management of severe perinatal asphyxia or death of the newborn at or near term. Perinatal asphyxia is a serious and often unexpected pathology, requiring urgent multidisciplinary care (obstetric - pediatric - intensive care, etc.) with a high level of technical expertise and care coordination. Because of its rarity and complexity, it may be subject to suboptimal care. The aim of this study is to provide feedback within the center itself, coupled in 1/3 of cases with a confidential investigation into the search for and understanding of suboptimal care. Primary endpoint: Frequency of optimal or non-optimal maternal and neonatal management of hypoxic-ischemic encephalopathy (AIE) or neonatal death related to severe perinatal asphyxia.

The RENATO trial is a multicenter randomized controlled trial that evaluates the efficacy of pioglitazone to improve renal outcomes in ANCA-associated vasculitis. Patients with biopsy-proven kidney involvement of ANCA vasculitis will be included in this trial at diagnosis. All patients will receive a standard of care immunosuppressive (SOC) therapy combining corticosteroids and rituximab (375 mg/m2/week for 4 consecutive weals followed by 500 mg re-infusion every 6 months). They will be randomized 1:1 to receive either pioglitazone 30 mg/day or placebo for 6 months, on top of SOC. The primary objective of this trial is to demonstrate that pioglitazone reduces kidney damage, reflected by the early improvement of proteinuria and serum creatinine levels. The secondary objectives will be to assess the efficacy of this drug on the reduction of hypertension and metabolic effects of glucocorticoids, to measure its impact on vasculitis activity and to evaluate the safety profile of pioglitazone in this population.

Suspected acute or subacute cardiovascular diseases-including chest pain, dyspnea, and palpitations-are among the most common reasons for unscheduled emergency department visits and pre-hospital referrals. Despite this high clinical burden, the diagnostic yield is often limited, with a frequent mismatch between initial clinical suspicion and final diagnosis, contributing to substantial healthcare utilization and hospitalization rates. Current evidence is largely focused on specific conditions such as acute coronary syndromes, heart failure, arrhythmias, or pulmonary embolism, and rarely integrates the full spectrum of clinical, biological, and imaging data obtained during initial evaluation. To address this gap, we will establish a prospective cohort of all consecutive patients referred to the ambulatory day-hospital cardiology unit at Lariboisière University Hospital. This unit acts as a specialized downstream referral structure within the emergency care pathway, receiving patients after triage by emergency physicians, pre-hospital regulation services (SAMU), mobile intensive care units (SMUR), or emergency departments. Although it does not capture all suspected cardiovascular emergencies, it represents a selected real-world population deemed to require specialized acute cardiology assessment. The primary objective is to assess the frequency of cardiac conditions diagnosed in this cohort. Secondary objectives include characterization of patient profiles and diagnostic pathways; evaluation of the diagnostic and prognostic performance of clinical, biological, imaging, and multimodal parameters using final Heart Team diagnosis as reference; analysis of prior health history and healthcare utilization; and assessment of the medico-economic burden of suspected acute cardiovascular disease. The study will further support the development of a dedicated biobank and the validation of next-generation biomarkers, including AI-driven and voice-based markers, as well as decision-support algorithms for binary classification of cardiac involvement. Through integration of multimodal data and linkage with national health records, this approach aims to improve diagnostic accuracy, risk stratification, and understanding of the healthcare impact of acute cardiovascular presentations in a real-world setting.

This study aims to investigate the impact of platelet concentrate (PC) transfusions on endothelial function and the systemic inflammatory response in thrombopenic patients admitted to intensive care who require prophylactic platelet transfusions. Endothelial function will be measured using a laser Doppler device coupled with an acetylcholine iontophoresis system that is applied to the skin.

Acute respiratory distress syndrome (ARDS) is a severe lung condition that often requires invasive mechanical ventilation in the intensive care unit. In these patients, setting the ventilator appropriately is essential to improve oxygenation while limiting ventilator-induced lung injury. One important ventilator setting is positive end-expiratory pressure (PEEP), which helps keep the lungs open. However, the optimal PEEP level may vary from one patient to another. The recruitment-to-inflation ratio (R/I ratio) is a bedside measurement used to estimate the potential for lung recruitment during a decrease in PEEP. It compares the compliance of the lung volume recruited by PEEP with the compliance of the already aerated lung. A higher R/I ratio suggests that increasing PEEP is more likely to reopen collapsed lung units, whereas a lower R/I ratio suggests limited recruitability and a higher likelihood that additional pressure would mainly distend lung areas that are already open. In clinical practice, the R/I ratio is increasingly used to guide PEEP adjustment, with the aim of improving recruitment and oxygenation while avoiding unnecessary increases in airway pressure. However, although the R/I ratio is used in routine care, there are currently no data demonstrating that this measurement is reproducible when repeated in the same patient under similar conditions. The hypothesis of this study is that the R/I ratio is reproducible when measured twice in the same patient under stable conditions, including no significant changes in ventilator settings, hemodynamic status, or ongoing treatments. This prospective, multicenter, non-interventional study will include adult ICU patients with ARDS who are receiving invasive mechanical ventilation, deep sedation, and assist-control ventilation. For each patient, airway opening pressure will be assessed, and the R/I ratio will be measured twice on the same day by a trained clinician, between 20 and 120 minutes apart, without changes in ventilator settings or treatments likely to influence the measurement. The main objective is to evaluate the within-patient reproducibility of the R/I ratio. Secondary objectives include describing changes in airway opening pressure and R/I ratio over time, assessing the reproducibility of expired tidal volume during the maneuvers, and evaluating the clinical tolerance of these ventilatory measurements. The study will include 80 patients across 4 French intensive care units. No additional intervention outside routine care will be performed. Clinical, ventilatory, and biological data already collected as part of usual care will be recorded.

PORTAL-4D is a prospective, interventional, non-randomized, parallel-group diagnostic study conducted at Pitié-Salpêtrière Hospital (Paris, France). Portal hypertension is the main driver of hepatic decompensation and is associated with ascites, variceal bleeding, hepatic encephalopathy, and reduced survival. The current gold standard for assessing portal hypertension is the invasive hepatic venous pressure gradient (HVPG) measurement performed via the transjugular route. However, HVPG is invasive, operator-dependent, and limited to specialized centers. A reliable non-invasive alternative is therefore highly needed. 60 adults patients with cirrhosis will be enrolled and divided into two parallel groups: MASLD group (n=24): Patients with compensated cirrhosis related to metabolic dysfunction-associated steatotic liver disease (MASLD). TIPS group (n=36): Patients with decompensated cirrhosis referred for transjugular intrahepatic portosystemic shunt (TIPS) placement. The primary objective is to assess the correlation between invasive HVPG values and 4D-flow MRI parameters. Secondary objectives include evaluating the prognostic value of 4D-flow MRI in predicting portal hypertension-related complications and post-TIPS outcomes within 6 months. The study is expected to validate 4D-flow MRI as an non-invasive diagnostic and prognostic tool for portal hypertension, potentially improving patient selection for TIPS and reducing reliance on invasive procedures.

Acute heart failure (AHF) is a major cause of acute dyspnea in emergency departments (EDs), driven primarily by venous congestion, which can lead to hepatic congestion and risk of subsequent liver dysfunction. Current diagnostic tools include clinical evaluation, biomarkers, and imaging (Chest X-Ray or echography), are often limited by delayed results, variability, and suboptimal accuracy in emergency settings. Fibroscan®, a non-invasive device originally designed to assess liver stiffness in chronic liver conditions, has shown potential in detecting liver congestion linked to heart failure. Studies have highlighted significant correlations between liver stiffness measurements (LSM) and markers of venous congestion, such as central venous pressure and adverse outcomes in heart failure patients. Preliminary findings suggest that LSM could provide rapid, bedside insights into systemic congestion, offering a promising avenue for improving diagnostic workflows in acute care. While prior research has mainly focused on chronic heart failure or small study populations, further investigation is needed to explore the utility of Fibroscan® in acute presentations of AHF within EDs. This could help address the limitations of existing diagnostic approaches and enhance patient management in time-sensitive environments.

This multicenter, non-randomized interventional study aims to assess coronary artery disease progression over 5 years in patients with genetically confirmed heterozygous familial hypercholesterolemia (HeFH), using coronary computed tomography angiography (CCTA). The primary endpoint is the visual evaluation of coronary stenosis using CAD-RADS v2.0, identifying changes between baseline (2018-2022) and study inclusion. The study will enroll 300 patients (100 protected, 200 non-protected) from La Pitié-Salpêtrière hospital and Saint Antoine Hospital (Paris). Participation lasts up to one week. Total study duration is 2 years, with extended follow-up through routine care data over 10 years.

Since 1985, growth hormone deficiency (GHD) in children has been the first condition treated with daily injections of recombinant human growth hormone. Noncompliance with daily growth hormone (GH) therapy is common. Several long-acting growth hormone (LAGH) treatments have recently become available for prescription in France after pivotal phase III trials demonstrated the non-inferiority of these LAGH compared to daily GH administration. To date, published data on LAGH in children are largely limited to clinical trials of GH deficiency (GHD). Contrary to what is observed with daily GH, body mass index increases during the first year of LAGH treatment. With the Somapacitan, the observed mean body mass index (BMI) (SDS) remained within the normal range, but with an increase from -0.17 to +0.39 in the LAGH group and a decrease from -0.25 to -0.49 in the daily GH group. In the Somatrogon study, BMI increased from -0.51 to -0.08 in the somatrogon group, while it decreased from -0.44 to -0.64 in the daily GH group. This increase in BMI was transient and then normalized over the 3-year follow-up. In June 2025, recent data from the experience of private endocrinologists in France (AFPEL) on the real-life use of somatrogon were presented at the congress of the French Society of Pediatric Endocrinology and Diabetology. They reported a +1 SD increase in BMI during the first months of treatment in a cohort of 99 children, but an improvement was observed after prolonged treatment. However, significant and persistent weight gain was observed in some patients, with a marked increase in abdominal adiposity. Some discontinued LAGH treatment in favor of daily GH. Longer-term, real-life data are therefore needed to better understand the changes in BMI in these children treated with LAGH.

"Candida auris is an emerging fungus that can cause severe infections, particularly in hospitalized patients, and is often resistant to multiple antifungal treatments. Rapid and accurate detection of this pathogen is essential to control its spread in healthcare settings. This study aims to evaluate the clinical performance of the NG-Test® Candida auris rapid diagnostic test (RDT), developed by CEA and NG Biotech. The test uses immunochromatography and can detect Candida auris in about 15 minutes. Its results will be compared to the reference method, MALDI-TOF, performed on colonies grown from routine patient samples. Both retrospective (using stored isolates) and prospective (using new isolates) evaluations will be conducted. The study will measure the sensitivity and specificity of the test, and also include an assessment of its ease of use by laboratory staff. No additional samples will be collected from patients, and all testing will use de-identified isolates to ensure confidentiality."

The purpose of this study is to determine whether a single infusion of tocilizumab is effective in reducing the time to successful weaning from both supplemental oxygen and any respiratory support, in pediatric and adult patients with sickle cell disease (SCD) during acute chest syndrome (ACS).

Early diagnosis is a key factor in the prevention and management of rheumatic diseases. Rheumatic diseases are classically diagnosed based on criteria combining clinical, biological and radiological features. However, in up to 20% of the cases, diagnoses remain unstated and underlying rheumatic diseases unclassified, which might lead to delayed specific treatment and unfavourable clinical outcomes. In addition, conventional methods could lack sensitivity and specificity for early diagnosis. Biological samples are attractive targets for the early detection of articular damage because they allow for collection of multiple levels of information from the clinic and the laboratory\]. Biological samples most frequently collected from patients with rheumatic diseases are synovial fluid by joint aspiration, blood by venous puncture and tissue specimen by surgery. The investigators hypothesize that in challenging situations, novel biomarkers detected from synovial fluid or articular tissues using both conventional (e.g. histology, immunodetection, PCR) and innovative (e.g. Raman spectroscopy, nanospectroscopy) laboratory tests may help refining diagnosis and better classifying patients with rheumatic diseases.

The aims of this collaborative, interdisciplinary research project are to understand and describe the psychological impact of the announcement of a rare, serious disease present since birth and detected in the context of the systematic neonatal screening (DNS), in terms of the parents' experience, but also on the part of the medical team, in order to improve its process and the support it provides for the announcement of the diagnosis.

Ulcerative Colitis (UC) is a chronic Inflammatory Bowel Disease characterized by chronic inflammation of the colon. Composition of gut microbiota of UC patients is abnormal (dysbiosis). Ulcerative Colitis patients have an increased risk of Clostridioides difficile infection (CDI) and CDI complications (colectomy, death, recurrence). The reason for this increased risk in IBD patients is not fully understood. The decrease in the proportion of secondary bile acids, induced by microbiota dysbiosis in patients with UC could favor C. difficile infection. The main objective of the study is to describe the composition of bile acids (primary and secondary) in children followed for UC during relapse with or without CDI and to compare it to children with UC in remission and healthy controls. The composition of fecal microbiota will be also describe to correlate dysbiosis and bile acid abnormalities. And finally some fecal biomarkers will be study : short chain fatty acids, metabolic pathway of Tryptophan, and fecal Calprotectin.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare auto-inflammatory bone disease that primarily affects children and/or adolescents at a median age of 10 years. Until now, there is no consensus regarding the treatment of CRMO. Non-steroidal anti-inflammatory drugs (NSAIDs) are considered the first line of therapy with remission in approximately 30% of cases. If unsuccessful, several treatments are tried in addition to NSAIDs, including bisphosphonates and anti-TNFs. The effectiveness of bisphosphonates (including zoledronate) has been reported in clinical cases and/or retrospective series. They are said to be particularly effective in multifocal forms, mandibular and/or vertebral involvement, but no controlled trials have been conducted. Bisphosphonates have even been proposed as first-line therapy in spinal involvement. The only prospective study, is a phase II trial currently underway in Denmark to study the efficacy of zoledronate (NCT02594878) versus placebo in SAPHO (acronym, standing for Synovitis - Acne - Pustulosis - Hyperostosis - Osteitis) patients considered to be a very similar form of CRMO occurring in adults. In this context, this study proposes evaluate the efficacy of zoledronate compared to placebo in reducing pain at week 12 in children aged ≥4 and \<17 years with NSAID-resistant CRMO. Zoledronate will be administered in three escalating doses: 0.025 mg/kg at baseline (W0), 0.05 mg/kg at week 12 (W12), and 0.05 mg/kg at week 24 (W24). In addition to pain reduction, improvements in MRI findings will be observed, biological markers of inflammation, and quality of life in the zoledronate group. Although subjective, pain reduction remains the most widely used criterion in clinical practice to assess therapeutic efficacy. Zoledronate efficacy will therefore be assessed by the change in standardized pain score (0-10 scale) from baseline to week 12 as the primary endpoint, with additional pain assessments at weeks 4, 24, and 36 as secondary endpoints.

The EPICIRC SCLC project aims to improve our understanding and treatment of extensive-stage small cell lung cancer (ES SCLC), the most aggressive form of lung cancer that accounts for 15% of all cases. Despite current treatments, which combine chemotherapy with immunotherapy, the outlook for patients remains poor, with an average survival of just 12 months. Recent research has shown that this cancer can be classified into four subtypes, which respond differently to anti-cancer treatments. However, these subtypes may change over time, particularly during chemotherapy, which could explain why many patients eventually become resistant to treatment. Understanding how these subtypes evolve could pave the way for better treatment strategies, but it has been difficult to study these changes because new tumor samples are rarely collected after a patient is diagnosed. The EPICIRC SCLC project tackles this challenge by using liquid biopsies, a minimally invasive technique that analyzes circulating free DNA (cfDNA) found in patients blood. This approach allows to monitor changes in the tumor's molecular profile over time without needing additional tissue samples. By collecting and analyzing blood samples from patients at three key points-before treatment, after four cycles of chemo-immunotherapy, and at disease progression-the project aims to track the evolution of the tumor's molecular subtypes and identify patterns associated with treatment resistance. Using advanced epigenomic technologies, we will study how genes are regulated and how their activity changes during treatment. This will provide a detailed map of the tumor's molecular evolution and could uncover new targets for future therapies. In the long term, these findings would lead to more personalized treatment strategies, helping clinicians select therapies based on the specific molecular profile of each patient's cancer at different stages of their treatment.