Active clinical trials for "Fibrosis"

The general objective is to elucidate the mechanisms whereby sex hormones may modulate the severity of respiratory disease. An important component of this proposal is a systematic and intensive approach to characterize how the cellular and cytokine components of airway inflammation respond to fluctuations in sex hormone levels. The effects of menstrual fluctuations in levels of sex hormones on inflammation and bacterial load in respiratory secretions of CF patients will also be determined.

n2015, VERTEX company - producing already KALYDECO (IVACAFTOR, VX-770) potentiator molecule that is recommended for the treatment of CF patients aged ≥ 6 y, with CFTR mutation altering the channel regulation (class III mutations) as G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549Nou S549R) -was allowed by the Federal Drug Administration (FDA) and European Medicines Agency (EMEA) for producing and using ivacaftor combination (such as lumacaftor/ ivacaftor initially, and more recently tezacaftor/ivacaftor, tezacaftor/ivacaftor/VX-659, tezacaftor/ivacaftor/VX-445 and tezacaftor/ivacaftor/VX-152) in clinical trials for patient with cystic fibrosis, according to age and mutation eligibility criteria. Since 2016, the French patients homozygous for the p.Phe508del mutation and older than 12 years are able to be treated with the association LUMACAFTOR-IVACAFTOR and this French authorization is being extended for 6-11 years old children (while the European Commission has already granted an extension of the Marketing Authorization for lumacaftor/ivacaftor to include 6-11 years old children with cystic fibrosis since January 2018). Patients treated by lumacaftor/ivacaftor (or other ivacaftor new combinations) are closely monitored according to criteria established by the working group "New Therapeutic Approaches" of the French Society Cystic fibrosis. This study is a phase IV observational trial for a period of 1 year. In this context, the team aims at initiating a comprehensive monitoring of the lung and gut mycobiota and microbiota evolution under LUMACAFTOR-IVACAFTOR (or other ivacaftor combinations) treatment. This project is directly linked to the monitoring of cystic fibrosis patients who begin treatment with LUMACAFTOR-IVACAFTOR (or other ivacaftor combinations) in France. The pro- and eukaryotic microbiota analysis is based on the secondary use of sputum and stool samples associated with several clinical data of CF patients under ivacaftor combinations and follow-up during the 1st year of therapy. According to the French law, Lum-Iva-Biota project is a non-interventional study. It aims at demonstrating that changes in the hydration of secretions at the pulmonary and intestinal levels related to LUMACAFTOR-IVACAFTOR therapy (or other new generation of ivacaftor combinations) promote a change in the lung and gut mycobiota and microbiota profiles which may achieve the characteristics of the "healthy type" (in terms of composition, richness and diversity).

Variceal hemorrhage is a lethal complication in patients with cirrhosis and portal hypertension. Identification of varices needing treatment in compensated cirrhosis is, therefore, of great therapeutic and prognostic importance. The gold standard for diagnosing gastroesophageal varices and evaluating the risk of variceal hemorrhage is esophagogastroduodenoscopy. According to the Baveno VI consensus, for those with high-risk varices (HRV), either non-selective beta blockers or endoscopic band ligation is recommended for the prevention of the first variceal bleeding. However, the invasiveness and uncomfortableness during the esophagogastroduodenoscopy procedure has hindered its use in clinical practice, especially in patients with compensated cirrhosis. Sufficient accurate non-invasive tools for detection of HRV are warranted to safely avoid the use of esophagogastroduodenoscopy. Advanced technologies including next-generation sequencing and MALDI-TOF mass spectrometry have the potential to be applied in this field. The latter is a widespread adopted tool in clinical microbiology for rapid, accurate and cost-effective identification of cultured bacteria and fungi. Recently, microbiome and peptidome have been proved their roles in the end-stage liver disease (e.g. cirrhosis, hepatocellular carcinoma), which may exhibit predictive capacity of HRV. In the present study, the investigators aim to conduct a prospective, multicenter diagnostic trial in 12 sites in China, 1 site in Turkey and 1 site in Thailand to evaluate the diagnostic performance of the microbiome/peptidome-based model for HRV detection in compensated cirrhosis.

Aim of this study is to evaluate the correlation between the characteristics detected by the 7T MRI equipment and the histological composition of native explanted livers (group A), liver graft excluded for donation (group B) and surgical specimens of primary pancreatic tumour, which underwent pancreaticoduodenectomy (group C).

To prospectively study novel blood and lung biomarkers of disease activity in patients with IPF and other interstitial lung disease with the aims of prognostic modelling and disease clustering

To evaluate the effects of DAAs on HRQL in patients with liver cirrhosis secondary to chronic HCV infection

Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, shown to be prevalent in adults with cancer and common chronic comorbidities such as liver cirrhosis. The EWGSOP identified a grading for Sarcopenia into pre-sarcopenia (decreased muscle mass with normal strength and physical performance), sarcopenia (decreased muscle mass with decreased strength or performance), severe Sarcopenia (decreased muscle mass, strength and performance) . Sarcopenia has emerged as an independent predictor of poor prognosis in a variety of clinical conditions.Sarcopenia is clinically important because it can affectthe quality of life of patients with cirrhosis . Skeletal muscle mass is not only a good indicator of nutrition in patients with cirrhosis, but also has recently been shown to be closely associated with survival prognosis and postoperative complications inHCC. Combination of sarcopenia and the Model for End-stage Liver Disease (MELD) has been shown to be an excellent model for predicting prognosis in decompensated liver cirrhosis . Most patients awaiting liver transplantation (LT) are more or less in a state of sarcopenia. Several studies have reported that sarcopenia was associated with worse prognosis.In addition, sarcopenia may be associated with a higher risk of post-transplant infection . Assessment of sarcopenia in patients with liver cirrhosis:_ The European Working Group on Sarcopenia in Older People recommended that the definition of sarcopenia include not only low muscle mass but also low muscle function . They recommended cutoff values for muscle mass measurements (7.26 kg/m2 for men and 5.5 kg/m2 for women using dual X-ray absorptiometry, and 8.87 kg/m2 for men and 6.42 kg/m2 for women using bioimpedance analysis, handgrip strength (<30 kg for men and <20 kg for women), and usual gait speed (<0.8 m/s). Aim of the study To evaluate sarcopenia in different stages of liver cirrhosis by different diagnostic methods. To identify the prognostic value of CT in the diagnosis of sarcopenia . To identify effect of sarcopenia inliver transplant candidate. Patients and methods: Type of the study:the study is divided into two parts First part: observational descriptive cross sectional study. Second part: follow up of liver transplant candidate group (pre and post liver transplantation) Duration of study: expected duration of the study will be 1.5 years . The 1st part will include all patients admitted to the department for 1 year fulfill inclusion criteria . 2nd part will be 6 ms follow up after liver transplantation. Study population st part : Patients with liver cirrhosis will be evaluated for the presence of sarcopenia. nd part: 13 cases of liver cirrhosis already done liver transplantation in AL Rajhiuneversitiy hospital(which data already recoreded) and any cirrhotic pts will be prerared for liver transplantion within six months. Methods At the study entry, all candidates will be subjected to the following parameters (and 3 month after LT for liver transplant candidates only) Clinical history Clinical examination Abdominal ultrasound Laboratory investigation: Liver function tests Complete blood picture, Kidney function tests, Serum glucose, serum Na+ and K+ Hepatitis markers (HBsAg, HCV-Ab) Calculate: = Child Pugh score (Pugh et al., 1973) and MELD (Wiesner et al., 2003) scores for assessment ofliver cirrhosis. Anthropometric measurements: Triceps skin fold thickness (TSF) . Measure mid-arm circumference (MAC). Body mass index Hand grip to assess muscle strength Gait speed to assess physical performance Assessment of sarcopenia using CT scan: Assessment of sarcopenia using ultrasound: Assessment of sarcopenia using bioimpedance analysis

To obtain prospective real world data of the effect of lumacaftor/ivacaftor or tezacaftor/ ivacaftor on small airway disease in children aged 6-18 years with cystic fibrosis (CF) homozygous for F508del. The effect of the medication on small airway disease is evaluated by measurement of multiple breath washout (MBW) with its outcome parameter lung clearance index (LCI) and the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) cpmputed tomography (CT) score. In addition the relation between changes in LCI and PRAGMA-CF score is evaluated.

The respiratory system involvement in cystic fibrosis(CF) influences the prognosis and course of disease. Respiratory assessment is based on spirometry, but its main parameter, the maximal expiratory volume in the first second (FEV1), does not reflect the initial peripheral impairment of airways. Another pulmonary function test (PFT) validated for CF children follow-up is measurement of "gas trapping", reflecting ventilation inhomogeneity and incipient airways impairment. "Gas trapping" can be obtained by lung volume measurement (functional residual capacity, FRC) by plethysmography and helium dilution technique, but these tests are inconvenient for children due to their long length (~30min). A complete PFT is routinely performed once a year. It also includes a measurement of Lung Clearance Index (LCI) reflecting ventilation inhomogeneity. Capnography is a non-invasive PFT technique, does not require subject's active cooperation, is of short duration and could replace the traditional PFT for CF children follow-up. The capnograph is integrated into the device measuring LCI and data can be retrieved and analyzed afterwards. Capnographic indices reflect ventilation inhomogeneity. The hypothesis is that capnographic indices change in the presence/absence of "gas trapping" in CF children. The main objective is to show that the capnographic index of efficacy (EFFi) is significantly different between CF children "with gas trapping" and CF children "without gas trapping". The secondary objectives are: to compare the other capnographic indices between CF children "with gas trapping" and CF children "without gas trapping": the slope of the ascending phase, α; the slope of the alveolar plateau, β; the angle Q between α and β; the positive peak of the first-order derivative, F'CO2, which reflects the ascending phase; the first negative peak of the 2nd order derivative, F "CO2, which reflects the curvature between the ascending phase and the alveolar plateau. to compare the results of the capnographic indices with the results of the FEV1 in identifying the presence / absence of "gas trapping"; to compare the results of the capnographic indices with the results of the LCI in identifying the presence / absence of "gas trapping"

The study will be conducted over a 6 months period. For the first three months, the child will be accompagned with a connected companion. After this period, the companion will be removed for three months in oder to prove this companion could improve treatment adherence for children suffering from cytolisis fibrosis. This study will be conducted at the University Hospital Center of Rennes and Hospital Center of Saint-Brieuc.