Clinical trials

This study evaluates the analgesic benefit of two non-invasive brain stimulation techniques: high frequency repetitive transcranial magnetic stimulation (rTMS) and accelerated intermittent theta burst stimulation (aiTBS) - compared to sham stimulation, in patients with chronic neuropathic pain lasting at least 6 months. Transcranial magnetic stimulation, which is delivered by a coil positioned on the scalp over the motor cortex, generates a low-intensity, submotor-threshold electromagnetic field that noninvasively activates targeted brain regions involved in pain perception. The procedure is painless and non-invasive. Sham stimulation uses the inactive face of the same coil and produces an identical sound, ensuring that neither patients nor investigators know which stimulation is being delivered. Conventional rTMS has demonstrated moderate analgesic efficacy in neuropathic pain, but its effect is delayed and requires at least 5 treatment sessions. iTBS delivers the same total stimulation dose in a much shorter time (approximately 8 minutes per session versus 30 minutes for conventional rTMS) and enables accelerated protocols with multiple sessions per day, which have shown promising results in depression. This study compares aiTBS, rTMS and sham by a randomized controlled trial (RCT) with a crossover design: participants are randomized in a 2:1 ratio to receive either active stimulation (both techniques in sequence) or sham stimulation (both techniques in sequence). Each treatment phase consists of either 5 consecutive daily rTMS sessions or 5 aiTBS sessions delivered on a single day (with a 45-min pause between sessions). The cross-over will take place after a 4 to 6-week washout period between the two active or sham treatments. The total study duration per participant is from 10 to 12 weeks, with 11-12 in-person visits. Assessments include self-reported pain diaries numeric pain rating scale (NPRS), validated pain, psychosocial, and quality-of-life questionnaires, resting-state Electroencephalography (EEG) recordings, and transcranial magnetic stimulation (TMS) based measures of intracortical excitability and inhibition. The exploratory aim is to identify neurophysiological and clinical predictors of treatment response, to better personalize the treatment in chronic pain population.

Repetitive Transcranial Magnetic Stimulation (rTMS) of the motor cortex is a recognized analgesic technique for the treatment of fibromyalgia pain, which represents a largely unmet medical need. However, the effectiveness of motor cortex rTMS is inconsistent, being observed in only about 40% of patients and not always long-lasting. It has been previously shown that predictive factors for a lack of response to motor cortex rTMS include the presence of depressive symptoms, and that prefrontal cortex rTMS is not effective for pain, even though this treatment has proven efficacy in major depressive disorder. The hypothesis is that targeting both the motor and prefrontal cortices with rTMS will yield a particularly beneficial effect in fibromyalgia patients presenting with comorbid depressive symptoms. Given the absence of established biomarkers for predicting rTMS response, an additional aim will be to develop reliable indicators of rTMS efficacy, based on clinical phenotype and measurements of oscillatory patterns assessed by electroencephalogram (EEG) recordings.

The goal of this study is to compare the evolution of the density of small nerve fibers assessed with skin biopsies at the foot between two groups of patients with taxane-induced chronic neuropathic pain matched for sex and age: one group treated with applications of capsaicin 8% and a control group who received a systemic treatment. The hypothesis for the capsaicin 8% arm is that in the chronic phase, in the absence in the nervous environment of the toxic agent (in this case taxanes) causing the neuropathy and the functional modifications at the origin of pain, the new small fibers could regenerate without these pathological alterations. Our analysis will be based on the demonstration of structural abnormalities of small nerve fibers by means of skin biopsy, but also of functional abnormalities using four validated tests commonly used in this field: quantitative sensory testing (QST), laser evoked potential recordings, Sudoscan and confocal corneal microscopy.

This clinical investigation aims to evaluate the efficacy and safety of a home-based device providing electrical stimulation of the brain named transcranial direct current stimulation (tDCS ) , in patients with chronic pain who have been transiently relieved by repetitive transcranial magnetic stimulation delivered at hospital (less than one month benefit). The general objective is to show that these patients may best benefit from home based tDCS while rTMS performed in hospital has only limited and transient efficacy. Each participant will be randomized into one of two arms to receive during 3 months either active tDCS or sham tDCS. Neither the investigator nor the patient will be aware of the treatment. The efficacy will be assessed on pain intensity (primary outcome at 3 months) and several secondary outcomes (qualify of life, pain symptoms , global impression of change, pain relief, sleep, anxiety, depression) every month for up to 3 months. Safety will be assessed at each follow up visit for up to 3 months. The participants will be asked to self stimulate themselves with the device 5 days per week for about 20 minutes.

The primary objective of this study will be to assess the proportion of fibromyalgia patients with diffuse small-fiber neuropathy (i.e. in the upper and lower limbs) and compare this proportion to patients with other chronic pains (nociplastic, nociceptive) and with healthy controls. Our analysis will be based on the demonstration of structural abnormalities of small nerve fibers by means of skin biopsy, but also of functional abnormalities using four validated tests commonly used in this field: quantitative sensory testing (QST), laser evoked potential recordings, Sudoscan and confocal corneal microscopy. It will thus be possible to verify whether or not patients with small fiber neuropathy have a particular clinical profile in terms of pain, physical activity, comorbidities or pain impact.

Septic shock remains a leading cause of mortality in intensive care, and while fluid resuscitation (FR) is a cornerstone of early management, its benefit-risk balance is highly variable. Excessive fluid administration can cause venous congestion and organ dysfunction, while insufficient resuscitation risks hypoperfusion. Current strategies often rely on fluid responsiveness (i.e., increased cardiac output after fluids), but this does not guarantee improved outcomes, particularly if congestion ensues. This prospective, multicenter, observational study aims to assess the clinical impact of FR in septic shock patients who are fluid responsive. The primary objective is to evaluate changes in tissue perfusion and venous congestion markers following FR. Patients will be categorized into four response profiles based on the presence or absence of perfusion improvement and congestion worsening. Secondary objectives include exploring the prognostic implications of each profile (organ dysfunction, mortality), identifying pre-FR predictors of adverse responses, evaluating changes in congestion markers after passive leg raising (PLR), and performing phenotypic clustering and mediation analyses. Eligible patients are adults with septic shock requiring vasopressors and mechanical ventilation, with confirmed fluid responsiveness via echocardiography. Each patient will undergo standardized pre- and post-FR assessments, including cardiac ultrasound, Doppler of hepatic/portal veins (VeXUS), CVP, perfusion markers, and blood gases. Data on SOFA scores, organ support duration, and 28-day mortality will be collected. Approximately 170 patients will be enrolled across five ICUs experienced in advanced hemodynamic monitoring. Statistical analyses will include multivariate modeling, clustering, ROC curves, and mediation analyses. By identifying phenotypes of fluid-responsive but fluid-intolerant patients, the study aims to refine fluid management strategies and improve outcomes through more personalized care in septic shock.