Clinical Research Directory

Study on the Safety and Efficacy of Intratympanic Injection of Small Extracellular Vesicles Derived From Mesenchymal Stem Cells in Severe and Profound Sudden Sensorineural Hearing Loss

The goal of this clinical trial is to learn if small extracellular vesicles derived from mesenchymal stem cells work to treat severe and above sudden sensorineural hearing loss. It will also learn about the safety of small extracellular vesicles. The main questions it aims to answer are: 1. Does small extracellular vesicles combined with traditional drug treatment improve hearing even better in severe and above sudden deafness participants? 2. What medical problems do participants have with intratympanic injection of small extracellular vesicles? Researchers will compare small extracellular vesicles to dexamethasone to see if small extracellular vesicles work to treat severe and above sudden sensorineural hearing loss. In clinical Phase I trial, the investigators will complete the safety check and dose exploration. Participants will: 1. Receive traditional drug treatment in accordance with the "Guidelines for the Diagnosis and Treatment of Sudden Deafness (2015) 2. Receive small extracellular vesicles or a placebo tympanic injection additionally 3. Visit the clinic once every 2 weeks for checkups and tests 4. Receive tympanic injections of small extracellular vesicles ranging from low concentration to high concentration 5. Be evaluated for any adverse reactions In clinical Phase II trial, participants were randomly divided into a control group and an experimental group. Participants will: 6. Received intratympanic injections of small extracellular vesicles 3 times together with traditional drug treatment in experimental group 7. Received intratympanic injections of 5mg dexamethasone 3 times together with traditional drug treatment in control group, also for a total of 3 times Visit the clinic once 7 days , 1month and 3 months after treatment for checkups and tests of pure tone audiometry, speech audiometry, tinnitus disability scale and visual analogue scale assessment

Characterization of Extracellular Vesicles From the Cord Blood of Extremely Preterm New Borns and Their Correlation With Severe Morbidity and Mortality

This study aims to understand the role of extracellular vesicles (EVs) in extremely premature infants, those born before 28 weeks of gestation. EVs are tiny particles released by cells that carry important information about the body's condition. In extremely premature infants, blood vessels may not function properly, leading to serious health problems such as bleeding in the brain, lung injury, or severe infections. Researchers believe that analyzing EVs in the umbilical cord blood of these infants may help predict which babies are at higher risk of developing these complications. By studying the size, number, and type of EVs, the team hopes to identify early markers that can guide doctors in providing better care. The study will collect cord blood from 30 eligible infants born at the CHU of Montpellier. Blood samples will be processed to isolate platelet-poor plasma, which contains EVs. This plasma will be stored in a biobank, allowing future research on EVs and their role in extreme prematurity. EVs will then be analyzed in the laboratory to assess their characteristics and any links to severe health issues. The findings from this study could improve understanding of circulatory problems in extremely premature infants, help identify early predictors of severe complications, and inform better monitoring and treatment strategies. The creation of a plasma biobank also provides a valuable resource for future research to enhance care and outcomes for this vulnerable population.

The Effect of Consumed Berries on Extracellular Vesicle Signalling in the Body

This study examines how berry consumption influences the signaling and distribution of extracellular vesicles (EVs) in the human body. EVs are small bilipid-layered nanoparticles released by cells. EVs carry proteins, lipids, and genetic material, and play a key role in cell-to-cell communication. The composition of EVs reflects the state of their cells of origin, and EVs can affect other cells by delivering their biological contents. EVs offer significant potential for both diagnostics and new therapies. Recent research has shown that EVs can be found in blood, urine, sweat, and can even cross biological barriers such as the blood-brain barrier and placenta. Many living organisms, including mammalian cells, bacteria, and plants, release EVs. Berries such as cloudberries and lingonberries have demonstrated positive effects on gut microbiota and metabolism, supporting digestive and metabolic health. In this study, a nutritional intervention will be conducted to investigate the effects of berry consumption on extracellular vesicle signaling of human cells and the gut microbiota, as well as the biodistribution of berry-derived vesicles in the human body.

Characterization of EVs (Extracellular Vesicles)/miRNAs (microRNAs) From Human Follicular Fluid

* Background Extracellular vesicles (EVs) are membrane-bound vesicles found in all biological fluids. They contain various regulatory molecules, including microRNAs (miRNAs). It is hypothesized that EVs in human follicular fluid (the fluid surrounding the oocyte within the ovary) play a crucial role in oocyte development through these miRNAs. * Research Question Is there a difference in miRNA expression in EVs in human follicular fluid based on the patient's age, the maturation stage of the corresponding oocyte, and/or the ploidy status of the resulting embryo (euploid in the case of a normal chromosome count vs. aneuploid in the case of an abnormal chromosome count)? * Methodology This prospective study will include patients in two age groups (≥ 38 years vs. ≤ 32 years; 7 patients per group) undergoing an ICSI treatment (intracytoplasmic sperm injection) in combination with a coPGT-M treatment at Ghent University Hospital. PGT-M (pre-implantation genetic testing for monogenic disorders) is an IVF/ICSI procedure in which an embryo biopsy is performed on day 5 or 6 of embryo development to test for known genetic disorders that could be inherited from one or both parents. With the coPGT-M technology or comprehensive PGT-M, in addition to detecting known genetic defects, any additional chromosomal abnormalities in the embryo are also identified. An embryo is considered aneuploid if its chromosome number is abnormal. For the participating patients, follicular fluid and plasma will be collected, and consent will be requested to store non-developing oocytes and embryos from the ICSI treatment. Inclusion will take place on day 10 of ovarian stimulation if the patient meets the inclusion and exclusion criteria and at least 5 follicles are confirmed to be growing. * Follicular Fluid (residual material): After oocyte retrieval, follicular fluid will be collected from 2-10 follicles per patient. EV isolation from this follicular fluid will be performed using the optimal technique determined in a preceding experiment (ID 18220, see 'Relations', comparison of 3 existing techniques to determine the optimal EV isolation technique from human follicular fluid). RNA extraction followed by miRNA sequencing will be used to assess differences in miRNA expression based on age (≤ 32 years vs. ≥ 38 years), oocyte maturation stage (mature vs. immature), and the ploidy status of the resulting embryo (euploid vs. aneuploid). In addition, the following hormone concentrations will be determined in the follicular fluid: estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). * Plasma: For participating patients, an additional blood tube will be taken during each blood sample/infusion placement within the standard-of-care IVF/ICSI treatment from day 10 of ovarian stimulation until the day of oocyte retrieval. EV isolation and RNA extraction will be performed on plasma samples of the ovulation trigger day and oocyte retrieval day. MiRNA sequencing of these samples will be correlated with the miRNA expression of EVs in follicular fluid.

Optimization of the Isolation Protocol for Extracellular Vesicles (EVs) From Human Follicular Fluid

Background: Extracellular vesicles (EVs) are membrane-bound vesicles found in all biological fluids, containing various regulatory molecules, including microRNAs (miRNAs). It has been suggested that the EVs in human follicular fluid (the fluid surrounding the oocyte within the ovary) play a crucial role in oocyte development through these miRNAs. However, several methods exist for isolating these EVs from follicular fluid. Before further research can be conducted on the pathophysiology and potential diagnostic and therapeutic applications of these EVs and their content, the optimal isolation technique must be determined for future studies. Each method has its advantages and disadvantages, and the purity and efficiency may vary between species and different biological fluids. There are only a limited number of studies comparing the various techniques for application in human follicular fluid. Objective: This study will compare the three most commonly used techniques for isolating EVs: size-based, sedimentation-based (differential ultracentrifugation), and buoyancy-based isolation techniques. Methodology: In this prospective study, follicular fluid will be collected from four patients undergoing transvaginal oocyte retrieval following ovarian stimulation at Ghent University Hospital. Patients over 40 years of age or with endometriosis, adenomyosis, or PCOS (polycystic ovarian syndrome) will not be included in this study. During the oocyte retrieval procedure, follicular fluid will be collected from 2-4 oocytes per patient. Since follicular fluid is not used in the patient's treatment (residual material), it does not affect the treatment. After collection, the three isolation techniques will be applied to each sample. The techniques will be compared in terms of purity (absence of contamination) and efficiency (EV concentration) using transmission electron microscopy, nanoparticle tracking analysis, and western blotting.

ExoLuminate Study for Early Detection of Pancreatic Cancer

ExoLuminate is a nationally-enrolling registry study designed for earlier detection of cancer in patients at elevated risk or clinically-suspicious for pancreatic ductal adenocarcinoma (PDAC). Those with elevated risk for PDAC can include individuals with intraductal papillary mucinous neoplasms, family history of pancreatic cancer, germline mutations in genes known to be associated with cancer, and a personal or family history of pancreatitis. The goal of the study is to compare the performance of ExoVerita™ assay in early detection of PDAC to current standard-of-care methods of surveillance.

MSC-EVs in Acute/ Acute-on-Chronic Liver Failure After Liver Transplantation

Acute liver failure (ALF) refers to a potentially reversible disorder that was the result of severe liver injury, with an onset of encephalopathy within 8 weeks of symptom appearance and in the absence of pre-existing liver disease. Acute-on-chronic liver failure refers to a liver failure syndrome in which some patients with chronic liver disease with relatively stable liver function suffer from acute liver decompensation and liver failure due to the effects of various acute injury factors. Liver transplantation is the only curative treatment for this type of end-stage liver disease. The potential of MSCs to repair or regenerate damaged tissue and suppress immune responses makes them promising in the treatment of liver diseases, especially in the field of liver transplantation. Many studies have shown that MSC-based therapies can reduce the symptoms of liver disease due to their paracrine effects. Therefore, compared to the cells they derive from, mesenchymal stem cells-derived extracellular vesicles (MSC-EV) are gradually gaining attention for their enhanced safety, as they do not replicate or cause microvascular embolism, and can be easily stored without losing their properties. It represents a novel and effective cell-free therapeutic agent as alternative to cell-based therapies for liver diseases, and liver failure was also concerned. This study was designed to evaluate the safety and tolerability of MSC-EV in acute-on-chronic liver failure after liver transplantation.

Study of Extracellular Vesicles (EV) in Patients Undergoing CAR-T Cell Therapies

Patients with refractory/relapse hematologic oncology disease may benefit from innovative therapy such as Car-T cells. Factors strongly predictive of outcome and response are unknown. Extracellular vesicles are recognized as a mode of intercellular communication and are reminiscent of the cell of origin. They are currently candidates to be biomarkers for this biomarker of phenomena occurring in tissues. The working hypothesis is that they may be predictive of outcome and toxicity, as some preliminary data have suggested. Therefore, the aim of the study concerns I dentification of potential CAR-EV biomarkers associated with neurological toxicity after infusion of CAR-T cells.

The MULTISITE Study

This study will investigate potential correlations and relationships between obesity and organ-specific complications, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic fatty pancreas disease (NAFPD) and fatty kidney. Furthermore, it will investigate how and if a lifestyle-induced weight-loss intervention decreases liver fat and improve NAFLD. Furthermore, the study will investigate if extracellular vesicles (EVs) can be used as a biomarker for early detection of any of the above-mentioned by comparing obese individuals with NAFLD and metabolic syndrome with both normal weight controls and obese individuals without NAFLD and metabolic syndrome. Lastly, it will investigate if weight changes and the resulting improvement of NAFLD are accompanied by changes in liver-specific extracellular vesicle (EV) phenotypes.