Clinical trials

The objective of this research project is to evaluate the biological effects of long-chain omega-3 supplementation, administered in an optimized, high-purity formulation (EPA:DHA 6:1, \>95% v/v), as an adjunct to standard-of-care treatment in patients with pulmonary arterial hypertension (PAH). The expected results are confirmation in humans of our preliminary data, namely a beneficial effect on systemic inflammation and pulmonary endothelial dysfunction in PAH. If our hypothesis is confirmed, omega-3s could constitute a complementary nutritional approach to current PAH therapies, subsequently requiring validation through a larger-scale, randomized, controlled study.

Dementia with Lewy bodies (DLB) is a neurodegenerative disease diagnosed primarily based on the presence of cognitive decline, which may include difficulties with memory, attention, and more. Additionally, at least two of the following symptoms are needed for a probable diagnosis of DLB, and at least one for a possible DLB diagnosis (McKeith et al. 2017 and 2020): * Fluctuations in cognition, attention, and/or alertness * Visual hallucinations * Spontaneous parkinsonism * REM sleep behavior disorder Patients with DLB can experience cognitive deficits that can fluctuate and can vary for each patient. These may include deficits in memory, executive functions (planning and organizing), attention, visual processing, and language. This study aims to evaluate the effect of red-light therapy, delivered using a helmet that contains small LED lights, in patients with DLB. Participants' cognitive functions, clinical symptoms, quality of life and functional cerebral connectivity will be evaluated before starting therapy and again after three and six months of twice daily therapy use. As DLB also indirectly affects caregivers, the caregiver's quality of life and burden will also be evaluated before and at three and six months of therapy use by the participant. The study's inclusion period is 24 months and the duration of participation for each patient is 8 months (+/-10 days) maximum.

The OPTIMISTE program is based on a structured postoperative follow-up centered on patients' subjective perception of recovery using validated Patient Reported Outcome Measures (PROMs), including the mQoR-15f score. Follow-up is delivered by specifically trained nurses and embedded in a decompartmentalized care model combining in-person and remote interactions, integrating hospital teams and primary care professionals within a coordinated pathway. OPTIMISTE was recently evaluated in a multicenter randomized controlled trial, the SUPPORT study (NCT06182254), which included 280 patients. The study demonstrated a significant impact of PROM-based follow-up on perceived recovery at postoperative day 35, and more importantly, an approximately 50% reduction in the proportion of patients with persistent opioid use at that time point. Although this was a secondary endpoint, the findings suggest that active postoperative monitoring centered on patient-reported outcomes and rapidly relayed to community care providers represents a major lever for preventing opioid misuse after surgery. However, these results require further confirmation and refinement. First, the effect on persistent opioid consumption needs to be validated as a primary endpoint. Second, despite the benefit observed, more than 12% of patients in the intervention group still exhibited persistent opioid use five weeks after surgery, compared with 21% in the control group. This residual persistence, although reduced, remains clinically concerning and indicates that the current OPTIMISTE model does not yet fully prevent unanticipated prolonged opioid exposure. The hypothesis of the present protocol is that the effectiveness of OPTIMISTE in reducing postoperative persistent opioid use can be strengthened through earlier, more individualized and primary-care-driven management. This enhancement relies on better mobilization of community healthcare professionals - general practitioners, community nurses and pharmacists - supported by digital health tools and reinforced coordination channels such as secure platforms, teleconsultations and structured transmission of PROM scores. By systematically integrating primary care providers into longitudinal postoperative follow-up guided by PROMs, the protocol aims to improve therapeutic responsiveness, reduce unjustified prolonged prescriptions and promote early tapering when clinically appropriate. The objective is to optimize hospital-community coordination in order to amplify the impact of the OPTIMISTE pathway on patient-perceived recovery and opioid stewardship. Ultimately, this research seeks to demonstrate that strengthening the role of primary care, combined with fine-grained assessment of patient-reported recovery, represents an effective, ethical and scalable strategy to improve the quality, safety and efficiency of postoperative care pathways while sustainably reducing persistent opioid use at both individual and population levels.

Extremely premature newborn infants (ELNs) admitted to hospital are exposed to stressful and painful stimuli, and often to maternal separation, which can affect their long-term neurological development. Child- and family-centred developmental care (CFDC) in neonatology aims to adapt the hospital environment to the needs of the child, support the continued presence of the family and help to improve their future. Specific assessment and appropriate analgesic treatment are therefore priorities for preserving the well-being and cerebral development of this population, which is particularly vulnerable to pain. Pain relief for certain procedures necessary for the care of newborn babies, such as venipuncture (PV), remains inadequate. Venipuncture is a common procedure in the first few weeks of life for very premature newborns. Its analgesic treatment is based on non-medicinal strategies largely carried out in the nurse's own role: non-nutritive suctioning combined with the administration of a sugar solution and wrapping. In line with the SDCEF philosophy, and reinforced by the "zero separation" concept, parental involvement in the treatment of their newborn's pain becomes natural and fundamental. A number of studies have shown the benefits of parents' presence and participation through specific isolated analgesic actions. Skin- to-skin contact (PAP) is one of these and has multiple benefits for the newborn. However, in practice, when a PV is necessary for a very premature baby, its use as a pain-relieving strategy is hampered by a number of obstacles. As NN are naturally oriented towards the maternal voice, using it is a new approach to analgesia. In an innovative study carried out in a single centre, direct maternal voice contact, in addition to the usual non- pharmacological analgesic strategies, reduced the NN's pain, without completely eliminating it during heel sampling (a skin incision known to be more painful than a PV). This analgesic strategy should therefore be combined with other non-pharmacological strategies, taking advantage of all maternal skills.

After acquired brain injury (ABI), persons can experience emotional and behavioral difficulties, that can be painful both for the person and his/her family. This clinical study aims at measuring the effectiveness of a third wave cognitive behavioral therapy called "dialectical behavior therapy" (DBT). DBT aims at teaching persons emotion regulation skills, interpersonal effectiveness skills, mindfulness and distress tolerance skills through group and individual sessions. The study's hypothesis is that DBT, in an adapted format for persons with ABI can lead to * a better quality of life, emotional and behavioral regulation, and self-esteem * decrease in problematic behaviors * progress in life goals * increase post traumatic growth and spirituality * better family functioning and lesser burden for care givers * experiencing more emotions and more free will 45 persons with an ABI sustained more than 18 month back, will follow a 3 phases, follow-up with care as usual for 5 months, followed by 5 months of DBT, followed by 5 months of care as usual + DBT monthly sessions. Self- and family-questionnaire will explore quality of life, emotional regulation, self-esteem, stress, anxiety, cognitive difficulties, family functioning and coping, post traumatic growth and spirituality and will be compared across the 3 phases. Results will be analyzed at a group level but also at an individual level (each patient separately) to test for decrease in unwanted behaviors and at a dyadic level (the person and his/her spouse) to test for the mutual effect of regulating emotions. Persons' memories will by analyzed at 3 time points by a linguistic analysis, and experience of free will after ABI will be analyzed by transcribed narratives of participants.

The prevalence of post-surgical lumbar neuropathic radiculopathy is approximately 30%. Poor response to the treatments recommended for neuropathic pain, namely antidepressants and/or gabapentinoids, requires the development of new techniques to prevent this chronic pain. Certain well-tolerated techniques, such as the administration of plasma enriched with platelets and fibrin (PRF), are increasingly used in regenerative medicine for their anti-inflammatory and analgesic properties. Thus, a periradicular intraoperative application of PRF may have an analgesic effect on the intensity of residual postsurgical neuropathic pain after disc herniation surgery.

Systemic sclerosis is a rare autoimmune disorder characterized by microangiopathy, activation of the immune system, and sclerosis of tissues including the skin. Facial involvement is frequent and disabling. It causes significant functional and aesthetic discomfort, and a major deterioration in quality of life. It results in a loss of suppleness of the skin and subcutaneous tissues, dysfunction of the temporomandibular joint, peribuccal rhagades, microstomia, and dry mouth causing difficulties in mouth opening, feeding, dental care, and weight loss. Facial involvement in systemic sclerosis can be assessed using the Mouth Handicap in Systemic Sclerosis (MHISS) score, a validated patient questionnaire assessing the functional and aesthetic consequences of systemic sclerosis on the face. Although common and disabling, facial involvement is underestimated and poorly managed. Immunosuppressive and/or anti-fibrosis drugs are not very effective. Facial rehabilitation could significantly improve the mouth handicap but facial rehabilitation is not currently performed in standard care in systemic sclerosis patients. The aim of the study is to evaluate the efficacy of a personalized rehabilitation program vs standard care in facial involvement of systemic sclerosis patients.

Kidney transplantation is the treatment of choice for end-stage chronic kidney disease. Kidney transplantation is at the first rank of solid organ transplantation in France, with 3,376 grafts performed in 2022. Immunosuppressive therapy, required to prevent graft rejection, exposes graft recipients to complications related to decreased immunity, including opportunistic infections and neoplastic complications. After the earlt post-transplantation period, up to 10% of kidney transplant recipients will require admission to the intensive care unit (ICU). The main reasons for admission are septic shock and acute hypoxemic respiratory failure. ICU stay has a significant impact on these patients with a mortality rate reaching 40%, that remains increased even after ICU discharge. Furthermore, an impact on graft function has been demonstrated, with deterioration of graft function in 1/3 of patients, and among those, up to one in two will require resumption of renal replacement therapy (RRT). Although the occurrence of septic shock or acute respiratory failure related to an infection is more common and severe, the optimal management strategy for immunosuppressors is not defined in kidney transplant recipients admitted to the ICU in those settings. Maintain a high level of immunosuppressive therapies may hinder the recovery from the acute critical condition. Furthermore, these treatments have a narrow therapeutic index; for instance, the management of calcineurin inhibitors is challenging in the ICU due to pharmacodynamic changes associated with the acute situation (distribution volume, organ failure) and the numerous potential drug interactions that carry inherent risks of overdose. the investigators hypothesize that a reduction in the level of immunosuppressive treatments could promote recovery in kidney transplant recipients admitted to the ICU for septic shock and/or acute hypoxemic respiratory failure, without adversely affecting the risk of rejection or long-term renal prognosis.

Disseminated Intravascular Coagulation is a severe complication of septic shock, associated with high mortality, whose diagnosis relies on complex scores that are rarely used in practice. Preliminary studies have shown that increased neutrophil fluorescence is associated with Disseminated Intravascular Coagulation and could reflect NETosis, a key mechanism of immunothrombosis. This study aims to validate neutrophil fluorescence measured on the SthemA 801 analyzer, alone or integrated into an artificial intelligence model, as an early, reliable, and routinely usable biomarker for the diagnosis of septic Disseminated Intravascular Coagulation.

Halitosis, or bad breath, affects about 30% of people worldwide and is most often caused by oral diseases such as periodontitis. To diagnose it, dentists usually perform a clinical examination and measure specific gases in the breath called volatile sulfur compounds (VSCs), which are responsible for bad odor. However, the equipment needed for this analysis is not widely available, forcing many patients to travel long distances. This study aims to determine whether breath samples can be collected and analyzed later, making remote diagnosis possible. Specifically, it evaluates whether the levels of these gases remain stable for up to 7 days after collection, with a variation of less than 20% considered acceptable. To do this, 100 adult patients with periodontal conditions will be included in a single-center study. During a single visit, patients will provide breath samples by exhaling into a special Tedlar bag and a syringe, which will then be analyzed immediately and again after 7 days using a device called OralChroma. Afull periodontal examination will also be performed, and patient information such as age and risk factors will be collected. The study will also examine how gas levels change over time and whether they are linked to gum disease. If the results confirm that the samples remain stable, this approach could allow patients to collect their breath at home and receive a diagnosis remotely, reducing the need for travel and improving access to care.

The number of surgical procedures performed annually exceeds 300 million worldwide and continues to grow. The management of the most common perioperative symptoms (pain, nausea/vomiting, constipation) represents a major public health challenge. In the context of postoperative pain management, a multimodal analgesia strategy is recommended in order to minimize opioid consumption. The opioid currently most commonly used is oral morphine sulfate. New therapeutic options are emerging, including sublingual sufentanil (Dzuveo®, 30 µg), which combines opioid-like effects with a faster onset of action due to its lipophilicity. The hypothesis of this study is that, because of its unique pharmacokinetic and pharmacodynamic profile, this new formulation is more effective than oral morphine sulfate in the treatment of postoperative pain and in the recovery of health status.

The objective of this study is to respond to frequent requests from patients who wish to reduce or even stop their antipsychotic treatment once they have achieved clinical stability. Psychiatrists are reluctant to respond to these requests because the method for safely reducing or stopping antipsychotic treatment remains poorly understood. The investigators want to verify the existence of an interaction between treatment strategy and psychotic phenotype (cycloid psychosis vs. non-CP), i.e., in terms of functional remission, the benefit of the dose reduction strategy compared to the maintenance strategy will be greater in the CP group than in the non-CP group. To this end, patients will be randomly assigned to four groups based on their phenotype and treatment strategy (CP-dose reduction; CP-dose maintenance; non-CP-dose reduction; and non-CP-dose maintenance). Several hospitals throughout France are participating in this study, in which a random draw (called randomization) will be conducted to determine whether the physician will propose reducing the antipsychotic dose or maintaining it at the same dose for the patient. Patients included in this study will be adults aged 18 to 60 who have been diagnosed with a schizophrenic spectrum disorder (SS): schizophrenia, schizophreniform disorder, schizoaffective disorder, or brief psychotic episode. The antipsychotics studied are: * second-generation antipsychotics: amisulpride, aripiprazole, olanzapine, quetiapine, risperidone; * first-generation antipsychotics: chlorpromazine, flupentixol, haloperidol, levomepromazine, loxapine, pipotiazine, zuclopenthixol. 288 patients will be included and followed for 24 months. The inclusion period is 48 months. Fourteen follow-up visits are planned, every month for four months and then every two months. During these visits, self-questionnaires or cognitive tests will have to be completed by the patient, the caregiver, and/or the treating psychiatrist. Three blood samples will be taken at inclusion, at 6 months, and at the end of the study, in particular to measure the level of medication in the blood.

While the reduced hemorrhagic risk of radial access for percutaneous coronary intervention compared to femoral access is well-established, its main complication remains radial artery occlusion, which can occur in up to 30% of patients. Anticoagulation is the primary preventive measure recommended in clinical practice to reduce the risk of this complication, typically involving heparin injection during the procedure in most centers. However, data on the effect of the timing of heparin injection are limited. The investigators hypothesize that injection of heparin before sheath insertion may reduce the rate of radial artery occlusion compared with injection after sheath insertion.

Apple-birch pollen-food allergy syndrome is particularly common in Northern and Central Europe (70% of patients allergic to birch pollen), and classically induces an oral syndrome that impairs patients' quality of life. Current treatment is based on food avoidance. However, evidence of the efficacy of this treatment is limited (small numbers, lack of validation with a control group, absence of double-blind evaluation of the primary endpoint in a challenge test against placebo). The aim of oral immunotherapy with raw apple is to improve the management of allergic patients by enabling them to acquire tolerance to raw apple and other rosacea.

Dystonia is a motor disorder caused by involuntary, intermittent, or sustained muscle contractions, leading to abnormal movements or postures. It can affect any body region and often results in significant functional disability and healthcare burden. Although its familial nature was recognized early on, the advent of high-throughput DNA sequencing has dramatically increased the identification of dystonia-associated genes. Dystonia now encompasses all modes of inheritance-autosomal dominant (e.g., TOR1A, KMT2B), autosomal recessive, X-linked, and mitochondrial-and over 100 genes have been implicated. Many forms involve structural variants (SVs) or copy number variations (CNVs), which are challenging to detect using standard short-read sequencing (srWGS). Molecular diagnosis is essential, ending the diagnostic odyssey and enabling genetic counseling, prognosis, reproductive planning, and-in some cases-targeted therapies. For instance, GNAO1-related dystonia may respond to deep brain stimulation, while dopa-responsive dystonia benefits from levodopa. Despite advances, srWGS has key limitations, especially for detecting repeat expansions, SVs, and phasing alleles. This likely explains the low diagnostic yield in dystonia compared to other neurological disorders, with over 70% of cases remaining unsolved. Long-read sequencing (lrWGS), such as Oxford Nanopore technology, overcomes many of these challenges by reading native DNA fragments thousands of bases long. It enables comprehensive detection of SNVs, indels, SVs, CNVs, methylation changes, and repeat expansions-including known and newly discovered pathogenic expansions (e.g., in NOTCH2NLC). It also allows phasing without parental samples, which is crucial in recessive cases. The investigators propose that lrWGS could significantly increase the diagnostic yield in dystonia, improving patient care, enabling appropriate genetic counseling, and paving the way for personalized treatment strategies.

OroDental anomalies are one of the phenotypical aspects of at least 900 rare diseases or syndromes affecting by definition less than 1 in 2000 individual within the population (almost 25 million persons in Europe). They are often described in association with other organs or system malformations, which is understandable, because the same genes and signalling pathways regulate the oral cavity formation or odontogenesis and the development of other organs. The various dental and orofacial anomalies can be classified by type (anomalies of tooth number, shape, size, structures of mineralized tissues, eruption, resorption, tumors; anomalies of oral mucosa; anomalies of tongue…), by signalling pathways and by syndrome families. These anomalies (for example hypodontia/oligodontia, amelogenesis imperfecta, dentinogenesis imperfecta…) become increasingly identified as diagnostic and predictive traits. Not only is it important to recognise, name appropriately and integrate these dysmorphic clues into the patient dysmorphology analysis but it is essential to synthesize the observations and confront them to existing data about similar orodental anomalies encountered in some of the corresponding mutant mouse models. Translational approaches in development and medicine, are relevant to gain understanding of molecular events underlying clinical manifestations and to enhance diagnostic accuracy. The aim of this study is to improve the knowledge, diagnosis and care of oral cavity pathologies encountered in rare diseases via the identification and gathering of national and international patient cohorts and to structure the molecular diagnosis behind these conditions via targeted next-generation sequencing assays. Data collection is implemented on validated accredited tools (databases) complying with the legal regulations about patient data protection and medical record collection. All information is anonymized. New effective diagnosis and therapeutic tools are being developed.

Emotional dysregulation (ED) is defined by difficulties in modulating the experience and expression of emotions, which are characterized by particularly marked reactivity, intensity, and duration. To improve the understanding of ED, its consequences in autistic women, and to be able to offer them appropriate treatments, it seems crucial to investigate the links between ED, known adversities during childhood, and premenstrual dysphoric symptoms. This study aims to characterize the variability of ED throughout a menstrual cycle by measuring it in an ecological real-life context. The variability of ED will be compared to that of women with borderline personality disorder (BPD), women with premenstrual dysphoric disorder (PMDD), and women without a diagnosed disorder.

Sepsis is a medical emergency whose prognosis depends on the early identification of patients at risk of septic shock, but the tools available in the Emergency Department remain insufficient. Neutrophils, key players in immunothrombosis, show alterations detectable via cell fluorescence (e.g., NE-SFL), which are strongly correlated with the severity of sepsis and septic DIC. The FLAMES study will evaluate, from the time of admission to the Emergency Department, the relevance of neutrophil fluorescence as an early biomarker of severity, either alone or integrated into an AI model based on the multiparametric data from the SthemA 801, with comparison to the Sysmex XN. It aims to address an unmet clinical need: the immediate stratification of the risk of severe forms of sepsis. Hypothesis: higher initial fluorescence will identify patients at risk of organ failure, septic shock, or DIC.

Internuclear ophthalmoplegia is a symptom frequently associated with multiple sclerosis (MS), although other etiologies are possible. Some patients do not meet the diagnostic criteria for MS at the time of the internuclear ophthalmoplegia episode but subsequently convert to MS. Studying this specific clinical situation may help enable earlier diagnosis of MS. The objective is to analyze the proportion of patients with isolated internuclear ophthalmoplegia who convert to multiple sclerosis and to identify factors associated with this conversion. The study hypothesis is that the presence of internuclear ophthalmoplegia is highly suggestive of multiple sclerosis, particularly when cerebrospinal fluid-specific oligoclonal bands are present.

The purpose of this study is to understand how different areas of the cerebellum (a part of the brain) control different functions and how they can be influenced by non-invasive brain stimulation. While researchers know that repetitive Transcranial Magnetic Stimulation (rTMS) can have positive effects on conditions like stroke and schizophrenia, they do not yet fully understand which specific stimulation settings work best or which exact parts of the cerebellum should be targeted for different symptoms. This study compares the effects of stimulation on two specific regions: * Lobule VIII: Linked to movement and motor learning. * CRUS I/II: Linked to attention, thinking (cognition), and predicting the timing of events.By comparing these areas, researchers hope to gain the information needed to develop better treatments for neurological and psychiatric disorders. This is a randomized, double-blind study involving 40 healthy volunteers. Participants will be split into two groups: * Group 1: Receives "exciting" (activity-increasing) stimulation. * Group 2: Receives "inhibiting" (activity-decreasing) stimulation. Each participant will attend three different test sessions in a random order: * rTMS targeting Lobule VIII * rTMS targeting CRUS I/II * Placebo (Sham) stimulation that looks and feels like the real thing but does not affect the brain. During each session, researchers will use brain imaging (fMRI) and computerized tasks to measure changes in brain connectivity and performance in motor and cognitive activities. There is no direct medical benefit to the participants. However, the results will help scientists create better therapies for patients with brain-related health issues The risks are considered minimal. Common side effects of rTMS include temporary mild headaches or a clicking sound during stimulation. MRI scans can sometimes cause mild discomfort or a feeling of closed-in spaces (claustrophobia). Researchers have put safety measures in place, such as hearing protection and constant medical supervision during scans, to minimize these risks.

The MYTH-MS study is a multicenter prospective study investigating the occurrence of clinical relapses in patients with relapsing-remitting multiple sclerosis (RRMS) in the absence of radiological activity on MRI. While MS relapses are typically associated with gadolinium-enhancing lesions on MRI, some patients present with acute neurological symptoms without radiological correlates, referred to as acute clinical events with stable MRI (ACES). The frequency, mechanisms, and clinical relevance of these events remain unclear due to limitations in previous studies. The primary objective is to determine the proportion of RRMS patients experiencing a relapse without gadolinium-enhancing lesions on early brain and spinal MRI. Secondary objectives include identifying clinical, radiological, biological, and psychological predictors, assessing neurologists' diagnostic accuracy, and evaluating clinical outcomes such as disability, cognition, and quality of life over a 6-month follow-up. A total of 136 patients with recent neurological exacerbations will be included. Each participant will undergo clinical assessment, cognitive and psychological evaluation, and early MRI, with follow-up at 6 months. An ancillary study will explore blood biomarkers (NfL, GFAP, and circulating DNA) to help differentiate true inflammatory relapses from ACES. This study aims to improve the understanding and diagnosis of MS exacerbations and to optimize patient management by reducing misdiagnosis and unnecessary treatments.

Palliative care patients frequently face a "symptom cluster" of pain (up to 96%), fatigue (up to 90%), and anxiety (up to 79%), which severely degrades their quality of life in their final months.The study is built on the concept of passive exposure therapy (VREP), which engages multiple senses to distract the brain from pain signals. By creating an "immersive distraction" or a "flow state," VR can activate the brain's reward networks and reduce activity in areas associated with pain perception. Unlike most existing VR research in palliative care which uses "passive" VR (like watching a 360-degree video), this study uses interactive VR. Patients can perform simple actions-like grabbing or dropping virtual objects-within a calming natural environment, which may better support their sense of autonomy and dignity. Because this is a pilot study, the "Go/No-Go" decision for future larger trials depends on a strict composite of three factors: * Adherence: The patient must complete at least 11 out of 14 planned daily sessions. * Duration: Each session must average at least 7.5 minutes of usable VR exposure. * Tolerance: The patient must experience no device-related serious adverse events and maintain a high average tolerance score (VRISE score ≥ 25).

Microcirculatory dysfunction is a key driver of organ failure and mortality in septic shock, characterized by endothelial injury and impaired vasoregulation. Despite its strong prognostic value, it remains unaddressed by current therapies. SGLT-2 inhibitors (SGLT-2i) have shown promising vasculoprotective, anti-inflammatory, and glucose-lowering effects that may help restore endothelial function, reduce vascular leakage, and manage stress-induced hyperglycemia-factors central to septic shock pathophysiology. Preclinical and clinical observational studies suggest potential benefits, but clinical research in this specific context is lacking. This trial aims to evaluate the efficacy and safety of SGLT-2i in septic shock patients with clinical signs of microcirculatory failure, addressing a critical unmet medical need. Septic shock management relies on rapid infection control, hemodynamic stabilization with fluids and vasopressors, and supportive care, with corticosteroids used in select cases. However, this standardized approach faces major limitations due to patient heterogeneity, treatment-related complications (e.g., fluid overload, vasopressor side effects), and rising antimicrobial resistance. Adjunctive therapies have largely failed to improve outcomes, reflecting the complex pathophysiology of septic shock. These challenges highlight a pressing need for novel, targeted interventions and a shift toward personalized treatment strategies. The investigators hypothesize that early administration of SGLT-2 inhibitors within 14 hours of septic shock onset in patients showing signs of microcirculatory dysfunction will improve 28-day outcomes mainly by targeting endothelial and microvascular injury. Expected benefits include reduced mortality and organ dysfunction, faster recovery with lower resource use, a favorable safety profile, and potential for global implementation as a cost-effective adjunctive therapy. This study will be a multicenter, prospective, randomized, and comparative double-blind trial. All patients admitted with septic shock in the ICU will be screened for trial eligibility criteria. After verifying the eligibility criteria and obtaining patient or family consent, or after an emergency inclusion procedure, eligible patients will be randomized in a 1:1 ratio to receive either Dapagliflozin (10 mg once daily) or matching placebo in addition to standard-of-care. Patients will be followed up for 1 year or until death, whichever occurs first.

Islet transplantation is associated with drastically improvement glucose control in people with type 1 diabetes. This treatment resulted in the disappearance of severe hypoglycemic events. However, its long-term effectiveness is limited by progressive loss of graft function. Currently, there is no standardized method to detect early dysfunction of the transplanted islets. This study aims to determine whether a parameter derived from continuous glucose monitoring (CGM), Time in Tight Range (70-140 mg/dL), is associated with pancreatic islet grafts function. The study hypothesis is that a decrease in Time in Tight Range reflects early loss of islet graft function.

Axial spondyloarthropathy (SpA) is the most common inflammatory rheumatism (1% of the general population) with important medico-economic consequences. Fatigue is a major feature of SA. It can be defined as a feeling of reduced muscle capacity, lack of energy and exhaustion. The fatigue reaches an abnormally high level (fatigue severity score (FSS) ≥4, called severe fatigue in this protocol) in more than two thirds of patients with SA. Skeletal muscle repercussions are present during SA. It is characterized by a decrease in exercise capacity independently of pain and ankylosis but is associated with a decrease in strength and muscle mass, the importance of which varies from one study to another. The link between fatigue (subjective sensation) and the skeletal muscular impact (objective) of SA has never been studied.