Active clinical trials for "Fibrosis"

The investigators are developing a new nuclear medicine imaging technique for measuring liquid absorption in the airways that can be applied to screen new medications being developed to treat cystic fibrosis (CF). The investigators believe that the absorption of the small molecule radiopharmaceutical Indium 111 diethylene triamine pentaacetic acid (In-DTPA) will indicate changes in liquid absorption in the airways and demonstrate whether new CF medications will be effective. In this study the investigators will determine whether the imaging technique will demonstrate similar results when it is repeated on different days. They will also determine how their results change when subjects utilize several common CF medications.

Patients with cirrhosis are particularly prone to infection which is frequently a precipitant of hepatic encephalopathy, renal failure and circulatory collapse. Bacterial infections are of particular concern in patients with cirrhosis because they are poorly tolerated. Sepsis and associated endotoxaemia whereby bacteria produce inflammatory particles occur in approximately 40% of hospitalized patients with cirrhosis and is a major cause of death. Gut-derived and blood-borne pathogens can induce an inflammatory response within the liver and spleen, which are the major organs that remove bacteria and their endotoxin (such as lipopolysaccharide - LPS and bacterial DNA itself) from the bloodstream. Several mechanisms have been identified and proposed in this process which depends upon a balance between the barrier functions of the gut and the 'detoxifying' capacity of the liver. People with established liver cirrhosis have been shown to have escape of endotoxin into the bloodstream produced by bacteria that reside in their intestines, which becomes more permeable or 'leaky'. Gut dysfunction is defined by changes in the types of bacteria within the gut and in overall permeability allowing bacterial products which would otherwise be contained within the gut to travel into the bloodstream and lymphatic system with detrimental effects elsewhere in the body. This passage of bacterial products is termed bacterial translocation, and it's effects on the liver and general immune system can be then be measured. It has now become recognised that certain types of white blood cells such as neutrophils and monocytes become dysfunctional and this predisposes to infection and may also have a more direct pathogenic role in hepatic encephalopathy. Thus neutrophil and monocytes may be a novel pharmacotherapeutic target in a condition where current therapies such as bowel aperients (e.g. lactulose) are inadequate. A therapeutic strategy utilising Rifaximin, a non-absorbable antibiotic, to modulate gut bacterial which produce ammonia, a chemical known to be important in the cause of hepatic encephalopathy, could potentially lower gut-derived systemic inflammation, endotoxaemia, infection and organ dysfunction in this population improving outcomes and prolonging transplant-free survival. We therefore plan to test if Rifaximin positively affects markers of immune dysfunction in patients with liver cirrhosis experiencing chronic hepatic encephalopathy after 30 days of treatment, as our primary research question. Positive results from this study would support further trials into the potential benefit of using Rifaximin to improve immune function, as well as reduce the recurrence of hepatic encephalopathy, in patients with liver cirrhosis.

The progression of lung disease in cystic fibrosis (CF) results inevitably in a reduction in exercise capacity. The assessment of fitness and exercise capacity in CF is an important measure of the impact of the disease process, particularly if it is repeated over time. With recent advances in clinical management, CF lung disease in children can be relatively mild and exercise tolerance good. The currently available field tests e.g. 3 minute step test, are often completed too easily. These tests provide limited information relating to maximal exercise performance. By contrast, the maximal CardioPulmonary Exercise Test (CPET), a progressive, incremental, gold standard exercise test with breath by breath analysis of expired gas, has proved to be a valuable means of assessing exercise response in patients with CF. Its only limitation is the requirement for specialist laboratory facilities, equipment and staff. A new field test for evaluating exercise capacity in children is needed. This should be portable, easy to administer and simple to perform by young children, while providing a higher intensity of exercise which correlates with day to day activity patterns of children, and clinically relevant information in the short term and longitudinally. This test needs to be a good surrogate measure of exercise capacity when formal CPET is unable to be undertaken. By providing accurate and useful information the results can be used to prescribe and train individuals with CF safely and effectively and can also be used in the short and long term for guidance of the medical management of these complex patients. The aim of this study is to develop and validate the use of a new incremental step test to assess exercise tolerance/capacity in children with CF, compare this with the gold standard CPET and to provide normative healthy control comparison data The main objectives of the study are To develop an incremental step test to assess exercise tolerance / capacity in children with CF. To compare the incremental step test with the gold standard CPET To assess the level of exercise response produced by the incremental step test To assess the correlation between independent variables of lung function measurements, age, weight and height with VO2peak and other exercise test outcomes To assess the repeatability and evaluate the normal variability of the new incremental step test To provide healthy control normative data for comparison

The treatment burden for patients with cystic fibrosis (CF) is significant and poor adherence has been well-documented. The investigators hypothesize that a coaching intervention will empower young adults with CF to manage their lives with CF and improve health-related quality of life (HRQoL). The main aim of the study is to establish the feasibility and acceptability of a life-coaching intervention.

Direct measurement of mucociliary and cough clearance (MCC/CC) has been used as a biomarker in cystic fibrosis (CF). Additional knowledge of the performance of this biomarker is needed to inform exploratory clinical trial design in support of programs to develop new inhaled therapies for CF. We hypothesize that MCC/CC measurements can be used to determine the durability of action of agents like hypertonic saline (HS) which increase epithelial lining fluid height.

The main purpose of this study is to determine whether psychological intervention is effective in improving quality of life, mood, and relationships among adults with hepatitis C virus and cirrhosis awaiting liver transplantation.

Serine proteases belonging to the elastase family are mainly responsible for lung tissue destruction as observed during cystic fibrosis. But anti-inflammatory therapies based on systemic or aerosolized protease-inhibitors administration, have not given the expected results until now. One reason would be the impaired access of therapeutic inhibitors to their molecular targets. It was recently shown that neutrophils actively secrete neutrophil extracellular traps (NETs) made of DNA that binds cationic proteases among other molecules. NETs together with DNA passively released from dead neutrophils contribute to the viscosity of CF expectorations which explains that rhDNase treatment fluidifies expectorations and improves the patient status. Preliminary experiments in our laboratory have shown that DNA degradation was associated with a significant increase of proteolytic activity in the sputum soluble fraction. However the efficacy of exogenous inhibitors is also improved in these conditions. Using the specific substrates and methodologies that we developed previously to measure cell-surface associated proteolytic activities, we will study the effects of DNase on the activity of individual proteases, their biodistribution in sputum and their regulation by potential therapeutic inhibitors. Enzymatic, immunochemical and microscopic (confocal and scanning) techniques will first be used for ex vivo studies on sputa freshly collected at the adult and paediatric CRCM in Tours, then on sputa from patients before and after administration of aerosolized rhDNase. We hypothesize that a better understanding of the biodistribution of neutrophil serine proteases and especially their binding to DNA will help designing new therapeutic strategies that facilitate inhibitor access to their protease targets.

To determine the pharmacokinetic profile of IV (intravenous) and PO (oral) formulations of linezolid among children with cystic fibrosis and establish a dose regimen that will be safe and effective.

The purpose of this study is to see if inhaled bicarbonate will increase the ability to cough up mucus in a person with cystic fibrosis.

To evaluate: the impact of combined antiviral therapy (Peginterferon plus ribavirin) on natural history of patients affected with HCV decompensated cirrhosis, after sustained virological response. A controlled study. safety and efficacy of antiviral therapy in this population by using a statistically significally number of patients as controls.