Active clinical trials for "Fibrosis"

Cystic fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians. It results in lung disease that affects quality of life and causes early death. Lung damage from CF starts in infancy and continues over time. Lung damage can negatively affect how the lung functions. It would be ideal to measure lung damage in CF patients in three instances: (1) During the first year of life after diagnosis by state newborn screening programs, (2) In children and adults over long periods of time (years), and (3) During times of illness (pulmonary exacerbation), to allow for better treatment and therapy to prevent loss of lung function. The lung is made of elastin, collagen and cartilage. When the lung is damaged by CF, these components break down into pieces that can be measured in urine, sputum and blood. These products may represent markers of lung injury. We believe that the levels of these markers will be increased over time in CF patients and even higher in patients who are sick with lung symptoms. The goal of my research is to measure the amount of lung breakdown products in urine, sputum and blood in infants, children and adults with CF during times when well and also during times of illness. I also hope to use new technologies involving the study of proteins and metabolites in samples like sputum, urine and blood to help provide new information regarding CF lung disease. These studies will help us to better treat CF lung disease.

Background: In patients with cirrhosis on secondary prevention of variceal rebleeding with non-selective beta-blockers (NSBBs), the risk of rebleeding and death is markedly higher in those failing to achieve a good hemodynamic response (HVPG reduction ≥20% of baseline values or ≤12mmHg). However a substantial proportion of non-responders will never rebleed, thus appearing protected by NSBBs although non-detected by HVPG response. This low sensitivity hampers risk stratification and diminishes the cost-effectiveness of assessing the hemodynamic response to NSBBs. This is particularly relevant in prevention of rebleeding since in this scenario the risk of rebleeding and of other portal hypertension related complications is very high, which calls for early institution of effective therapy. Baseline HVPG bears prognostic significance with regards to risk of developing varices, decompensation, hepatocellular carcinoma and death1,2,7,8,18-27. However, no studies have investigated whether adding data from baseline HVPG may improve the sensitivity of the criteria defining a good or poor hemodynamic response. Hypothesis: Adding data from baseline HVPG may improve the sensitivity of the criteria defining a good or poor hemodynamic response. Objective: Exploring the prognostic value of basal HVPG that better discriminate those non-responders who do not re-bleed under prophylactic treatment with NSBBs. Methods: Observational cohort study. Training set: patients from two longitudinal studies conducted at the Hepatic Hemodynamic laboratory of the Hospital Clínic of Barcelona to assess the prognostic value of HVPG changes during continuous therapy with NSBBs for preventing variceal rebleeding. Validation set for chronic hemodynamic response: patients from two longitudinal studies conducted at the Hepatic Hemodynamic laboratory of the Hospital de Sant Pau of Barcelona to assess the prognostic value of HVPG changes during continuous therapy with NSBBs for preventing variceal rebleeding; a third cohort composed of patients undergoing acute hemodynamic response to intravenous propranolol will be studied. All patients received a preplanned follow-up in the outpatient clinic at 1, 3, and 6 months, and every 6 months thereafter in the original studies. End-point: bleeding from portal hypertensive sources (esophago-gastric varices or portal hypertensive gastropathy) (defined according to Baveno criteria 32), death or liver transplantation. Ethical aspects: All patients have given their written informed consent to use their data in the original studies.

We have several ways to appropriately determine renal function in healthy patients and in several diseases, in cirrhotic population we dont have a precise tool that has sufficient precision that reflects glomerular function, although it has been reported that cystatin C, because of its nature could improve diagnostic accuracy to determinate the renal function in this population. The investigators hypothesize that glomerular filtration obtained from cystatin-C-derived formulas are more accurate when compared to creatinine-derived formulas with DTPA-Tc99 (diethylene-triamine-pentaacetate- technetium-99) as gold standard.

Given the treatment burden and excess morbidity and mortality associated with acute infective exacerbations in cystic fibrosis, a clear understanding of the mechanisms involved in the origins of an infective exacerbation and the response to antibiotics is vital to improving long-term outcomes in CF. This study will examine 3 areas of interest in CF exacerbations. Bacterial biodiversity and its clinical significance The role of bacteria which are able to rapidly mutate (hypermutators) Inter-bacterial communication and its role in infective exacerbations Study Hypothesis 1 Increased microbiological diversity represents a balanced community of bacteria. The presence of a diverse population of bacteria in CF infections therefore predicts a better outcome for treatment than when a population consists of a small number of more virulent organisms. Study Hypothesis 2 Pseudomonas aeruginosa hypermutators can mutate much more often than ordinary Pseudomonas aeruginosa bacteria. Hypermutators are likely to grow better when the bacteria are under stress, such as during antibiotic treatment or during an infection. They are, however, weaker organisms because of the multiple mutations they have undergone. Their presence does not relate to clinical outcome but may be associated with the emergence of antibiotic resistance. Study Hypothesis 3 Some Pseudomonas aeruginosa bacteria communicate with each other by secreting and responding to chemicals known as quorum sensing (QS)molecules. As well as affecting the behaviour of bacteria, these QS molecules can cause inflammation in the lung of CF patients. Selective growth of QS-producing organisms can trigger lung exacerbations in CF. If antibiotics kill this population of bacteria and QS molecule levels drop in the lung, patients recover from infection quickly. Failure to kill these bacteria with antibiotics allow QS molecule levels to remain elevated and patients to have prolonged infections.

The purpose of this study is to determine whether simvastatin is effective in the prevention of progression of porta hypertension in compensated cirrhosis patients.

Recently there is increasing reports of NEPHROGENIIC SYSTEMIC FIBROSIS(NSF) in patients with severe renal failure mainly in patients under dialysis in whom gadollinum is being used. The investigators will evaluate the prevalence and severity of NSF in patients with different degree of renal failure whom underwent imaging with Gadolinum.

The purpose of this study is to determine whether ultrasound or CT scanning is more effective at detecting early liver cancer in patients with advanced liver disease.

The investigators' Upstate Cystic fibrosis (CF) Care Center is very active in research. For example, in 2009, 68 of our 135 pediatric patients have been participating in 16 clinical trials. Sponsors often provide their study sites with spirometers to use for PFTs. These machines are meant to provide uniform PFTs results for studies, which include measurement of FEV1 values. In 2009, among the 52 patients at our Center who are 6-12 years old, 20 (38%) have been in studies with sponsor-provided spirometers. Among the 32 patients ages 13-17 years, 13 (40%) have been in studies with sponsor-provided spirometers. Anecdotally, the investigators have noted that FEV1 results obtained during clinical trials for our patients appear to be lower than those of our patients' usual values, especially with younger children. The investigators hypothesize that the apparent difference in PFT results might be related to the different incentives (if any) provided by study PFT equipment. Further, if this difference exists, the investigators believe that this may account for the apparent average decline in the lung function results of our patients over the recent years, given the large proportion of our patients who participate in clinical trials. Finally, the investigators hypothesize that younger children may be more affected by the difference in incentives than older ones. The purpose of this study is to collect an additional set of Pulmonary Function Tests (PFTs) using our regular clinic equipment, on all study subjects following their study PFTs if these are done with sponsor-provided equipment. The investigators will compare the results from both types of machines and report regarding differences identified.

Shortness of breath (dyspnea) during exercise is a major source of distress and is a commonly reported symptom in patients with cystic fibrosis (CF). Due to the investigators' poor understanding of how dyspnea develops, there are no treatments that consistently reduce dyspnea in this population. The investigators aim to acquire a more comprehensive understanding of the physiological mechanisms of exertional dyspnea in CF patients. This study will likely identify an important physiological mechanism of dyspnea in CF and may contribute to the development and use of effective treatments to reduce dyspnea in this population. The central hypothesis is that the impaired tidal volume (VT) response during exercise in CF, in the setting of increased ventilatory demand will give rise to different qualitative descriptions of exertional dyspnea compared with healthy age and sex-matched controls. Specifically, CF patients will select "increased work and effort" as their dominant descriptor of dyspnea up to the VT inflection/plateau. Beyond this point, CF patient's dominant descriptor will become "unsatisfied inspiration." In contrast, healthy control participants will report "increased work and effort" throughout all phases of exercise and will not report "unsatisfied inspiration", even after the VT inflection/plateau.

Chronic peripheral and splanchnic vasodilatation are the hallmark hemodynamic abnormality in cirrhosis and contribute to the pathogenesis of portal hypertension. Alterations in intestinal motility and bacterial overgrowth in gut may predispose to the development of bacteraemia and endotoxaemia in cirrhotic patients which play a role in the hyperdynamic circulatory syndrome of cirrhosis. Probiotic therapy is aimed at changing the make-up of the indigenous microflora by administering specific strains of non-pathogenic and potentially beneficial microflora. In this study, the investigators hypothesize that a modification in the composition of the endogenous digestive microflora by oral bacteriotherapy with high potency probiotic preparations could be a safe way to regulate the portal pressure. As there is a relative paucity in effective pharmacological treatment for portal hypertension, these novel and innovative therapy might provide important alternative or adjunct therapy to beta blockers in the clinical management of patients with portal hypertension. Aims and objectives To study in patients with cirrhosis and large varices whether probiotics and/or norfloxacin given for 2 months : achieve a reduction in HVPG alter the endotoxin and cytokine levels, and improve systemic inflammatory responses well tolerated. Inclusion criteria: Consecutive patients of cirrhosis with portal hypertension who fulfill the following criteria: Diagnosed cases of cirrhosis (by clinical, biochemical and radiological criteria with or without liver biopsy) No history of upper GI bleeding in the past Endoscopically documented large esophageal varices Exclusion criteria history of gastrointestinal bleeding patients who have received beta blockers for portal hypertension in the past 6 weeks. hepatic encephalopathy ongoing bacterial infection, Spontaneous bacterial peritonitis active alcoholism or illicit drug abuse alcoholic hepatitis Treatment with antibiotics in the preceding 2 weeks. presence of hepatocellular carcinoma, portal vein thrombosis serum creatinine>1.5 mg/dL, treatment with vasoactive drugs in the past 6 weeks, history of arterial hypertension, congestive heart failure or arterial occlusive disease, and Refusal to participate. Active smokers. Study plan: Ethical approval will be obtained prior to study initiation. Patients presenting to Department of Gastroenterology, GB Pant Hospital will be recruited in the study. Patients will be evaluated regarding the eligibility for the study. After being found eligible for the study, if the patient agrees to participate in the study, a signed informed consent will be obtained. Baseline HVPG will be measured in all patients and then they will be randomized into 3 groups:. Group 1: Beta blockers + placebo Group 2: Beta blockers + Norfloxacin (400mg BD) Group 3: Beta blockers + probiotics. (one sachet of VSL#3 BD) 30 patients will be enrolled into each group. The treatment will be continued for 2 months. The study design is a randomized double-blinded placebo controlled trial. Once patients have been enrolled, they will undergo baseline investigations. Blood will be drawn from both peripheral and hepatic veins and sent for routine parameters, pro-inflammatory cytokines (IL-1b, IL-6, IL-10, TNF-α, endotoxins, NO2 and NO3 levels, PRA, BNP). Samples will be stored at -70 ºC. Baseline vitals will be recorded. Patients will be called at the end of 1 month for assessment of compliance and then at the end of the study (2 months) to repeat the HVPG and the same parameters as at the time of enrollment End Points: Primary a. Change in HVPG levels as compared with baseline, to define responder (≥20% reduction in HVPG or ≤ 12 mm Hg). Secondary Change in digestive flora Reduction in serum and hepatic endotoxin and cytokine levels Assessment of improvement in the renal parameters and Systemic inflammatory response syndrome Improvement in the markers of oxidative injury Adverse effects