View clinical trials related to Sarcoidosis.
Filter by:Sarcoidosis is a systemic inflammatory disease characterized by unspecific granuloma formation. Our hypothesis is that granuloma formation and maintenance mainly relies on the overactivation of monocytes (Mo) and macrophages (Ma). To this end, the study aims (i) to define MoMa systemic signature in sarcoidosis, (ii) to characterize this signature in situ on tissue samples, and (iii) to identify causative factors that participate to the MoMa chronic overactivation. Thus, a cohort of sarcoidosis patients will be compared with tuberculosis patients. The MoMa systemic signature will be defined on whole blood (TruCulture model) and then in situ through different methods (multi-parameter spectral flow cytometry, RNA-seq, Luminex, imaging mass cytometry). The epigenome of monocytes will be studied thanks to CUT&Tag. The MoMa systemic signature will be defined ex vivo at different time points during the course of the disease with phenotypic, transcriptomic, cytokine and functional approaches. The previously identified signature will be studied in situ and completed by the characterization of granuloma architecture and microenvironmental interactions, which could be modulated by epigenetic modifications. Hence, the epigenome of monocytes will be analyzed in two groups (sarcoidosis and tuberculosis). These results would allow to better understand sarcoidosis physiopathology and, in fine, may raise new therapeutic strategies. Finally, the study could challenge the dogma on innate immunity/auto-inflammation versus adaptive immunity/auto-immunity/memory.
This is a double blinded, randomized, placebo controlled clinical trial of 40 participants with pulmonary sarcoidosis. Primary Objective: To assess the steroid-sparing efficacy and safety of oral metformin therapy in participants with confirmed progressive pulmonary sarcoidosis for participants with steroid dependent disease.
A phase 1b/2 study of XTMAB-16 in patients with pulmonary sarcoidosis
Sarcoidosis is a systemic granulomatous disease of unknown aetiology, mainly affecting the lungs and lymphatics. It affects people worldwide (incidence, 4.7-64/100000; prevalence, 1-36/100000/year). Although it is most often a benign acute or subacute condition, sarcoidosis may progress to a disabling chronic disease in 25% of the cases, with severe complications in about 5%, such as lung fibrosis, cardiac or neurosarcoidosis, defacing lupus pernio or blindness due to uveitis. When indicated, corticosteroids (CS) are the mainstay of treatment. Due to the kinetics of granuloma resolution, the usual and quite 'dogmatic' duration of treatment is said to be one year, following four classical steps. The long-term use of CS is hindered by cumulative toxicity and efforts have to be made to taper them, as quickly as possible, to the lowest effective dose. A recent report mentioned 39% of the CS-treated patients requiring a steroid-sparing agent. Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-malarial drugs that have been used since the 1960's as steroidsparing agents on the basis of a landmark study by Siltzbach reporting their efficacy in 43 patients with skin and intrathoracic sarcoidosis. Subsequently, two small randomized controlled trials have shown significant and prolonged improvement on pulmonary symptoms. Only small case series/reports have shown CQ/HCQ efficacy on extra-pulmonary sarcoidosis with response rates ranging from 67 to 100%. Nevertheless, CQ/HCQ are daily used for skin, bone, and joint sarcoidosis, as well as hypercalcemia. Nowadays, HCQ is preferred over CQ because of a lower incidence of gastrointestinal and ocular adverse reactions, which can be minimized by close attention to the dosage and regular retinal examination. Its profile of safety is well-known since it has long been employed to treat systemic lupus erythematous or rheumatoid arthritis. Its action is thought to rely on its ability to accumulate in lysosomes of phagocytic cells, to affect antigen presentation and reduce pro-inflammatory cytokines. The investigator hypothesize that HCQ may be an efficacious add-on therapy for extra-pulmonary sarcoidosis leading to a significant steroid-sparing effect.
The goal of this observational study is to elucidate the role of serum amyloid A (SAA) in the diagnosis and follow-up of sarcoidosis, including its prognostic value. The main questions it aims to answer are: - Whether, at the time of diagnosis, SAA is in correlation with other serum markers of granulomatous inflammation, interstitial disease and pulmonary fibrosis, lung function and radiologic characteristics of intrathoracic sarcoidosis, - Whether increased serum concentrations of SAA at the time of diagnosis act as a prognostic marker of progressive granulomatous inflammation and pulmonary interstitial disease. Patients will undergo standard diagnostic procedures for intrathoracic sarcoidosis, according to WASOG (World association of sarcoidosis and other granulomatous disorders) criteria. Two additional vials of blood will be taken at diagnosis and one vial at follow-up for serum processing and biomarker analysis. Healthy blood donors will represent our group of healthy controls.
Cardiac sarcoidosis (CS) is a complex disease that is characterized by the formation of inflammatory granulomas in the myocardium. The exact underlying pathophysiology of the disease is not yet fully understood, but it is believed to be related to dysregulation of the immune system. Despite significant progress in recent years, the disease remains difficult to diagnose, and there is a high risk of severe complications such as life-threatening cardiac arrhythmias, severe heart failure, and sudden cardiac death in affected patients. Moreover, the clinical presentation of CS can be similar to other inflammatory heart diseases or familial cardiomyopathies. Thus, it is challenging to differentiate between these diseases, which can lead to a delayed diagnosis and poor prognosis. It is unclear whether certain genetic variants play a role in the clinical course and prognosis of CS, which highlights the need for more research in this area. The diagnosis of CS requires cardiac or extracardiac biopsy with granuloma detection, which is an invasive and complex procedure. Consequently, the disease is thought to be underdiagnosed, and many affected patients may not receive timely treatment, resulting in excess mortality. Early diagnosis and immunosuppressive treatment, as well as defibrillator implantation if necessary, are crucial in delaying disease progression, preventing complications, and improving prognosis. To better understand the key molecular pathological mechanisms underlying the development and maintenance of CS, a prospective, multicenter, exploratory study has been initiated. The project involves the collection, storage, and analysis of biological samples from blood, myocardium, and lymph nodes of patients with cardiac sarcoidosis or cardiomyopathies that present clinically and image morphologically similar. The samples will be used for scientific investigations on disease mechanisms of cardiomyopathies as well as for identification of new biomarkers in cardiomyopathy diagnostics and for follow-up of therapeutic measures. The study will employ a range of classical biochemical methods such as ELISA, RIA, as well as more modern methods of molecular biology (single cell sequencing, single nucleus sequencing) and systems biology (genomics, metabolomics, or proteomics) to identify key molecular pathological mechanisms in the development and maintenance of CS. In addition, genetic analysis will be performed to investigate cardiomyopathy- and ion channel-associated genetic variants, which is critical for improving diagnostics and early, individualized therapy. The study will be conducted on a multicenter basis, with the Heart Center Leipzig serving as the initiator and lead center and the University Hospital Leipzig as the second study center. Biochemical and molecular biological analyses will be performed on behalf of the study management at the Heart Center Leipzig, the University Hospital Leipzig, and the Erich and Hanna Klessmann Institute for Cardiovascular Research and Development of the Heart and Diabetes Center NRW and Max Delbrück Center for Molecular Medicine in Berlin. In conclusion, CS is a complex and challenging disease that requires further research to better understand its underlying mechanisms and improve diagnostic and therapeutic strategies. The prospective, multicenter, exploratory study will provide valuable insights into the disease's key molecular pathological mechanisms and identify new biomarkers for better diagnostics and individualized therapy.
Airway involvement in sarcoidosis was demonstrated in a meaningful, albeit variable, proportion of patients through biopsy of the central, endoscopically visible airways. Ideally, biopsy of peripheral airways, nowadays possible with the introduction in the market of ultrathin bronchoscopes, might be associated with an increased diagnostic yield for the detection of granulomas.
Background: Sarcoidosis is an inflammatory disease, most commonly affecting the lungs and intrathoracic lymph nodes but can affect virtually any organ, sometimes manifesting as life threatening cardiac arrythmias. Some patients resolve spontaneously, whereas others get a chronic disease leading to for instance impaired lung function and cardiac failure. The most severe cases might need a transplantation. In the lungs, activated T cells are accumulated leading to release of cytokines, especially TNF-alpha is regarded as crucial for disease progression. Some segments of the T cell receptor and specific genes (HLA types) are connected to a resolving disease. More detailed knowledge about mechanisms why some experience a chronic disease course and others resolve spontaneously without treatment is to a large extent lacking. There is no cure, and despite treatment with immunosuppressants (often corticosteroids and cytotoxic agents), many patients experience a deteriorating disease. Aim: 1. Find biomarkers to be able to early predict which patients will develop a more severe/ chronic disease course and thereby enabeling early intervention before irreversible damage. 2. Predict which treatment is best for a specific patient, i.e. individualize treatment. 3. Find targets for new potential therapies. Methods: The majority of data is collected at investigations normally performed during diagnostic work-up for sarcoidosis. Most patients undergo a bronchoscopy with bronchoalveolar lavage (BAL) and some also lymph node punction through oesophagus with the help of ultrasound. The BAL fluid that remains after clinical analysis is used for research purpose. For patients undergoing lymph node punction, one extra punction is performed for research purpose. Extra blood samples are taken from all patients. The samples will mostly be used for studying T cells with immunohistochemistry, flow cytometry including activity markers, subtypes and receptors, but also cytokines and other cells (for instance B cells, NK and NKT cells). The patients are followed longitudinally, minimum 2 years. Some patients will undergo a second bronchoscopy 6-12 months after the first. Results from the immunological investigations will be correlated to disease course, genetics and result of treatment. Significance : By comparing the inflammation in several compartments (lung, lymph node , blood) at a molecular level with clinical disease course, genotype, and treatment response we hope to find biomarkers that can predict disease course and response to therapy. Thereby, we hope to be able to tailor therapy for each individual patient. By studying several compartments, the results may also help to improve understanding of how a systemic inflammation is distributed within the body, and thus also contribute to understanding of other inflammatory diseases.
The goal of this clinical trial is to learn whether semaglutide, an FDA-approved treatment for diabetes and obesity, is feasible and tolerable in patients with advanced lung disease. The main question[s] it aims to answer are: 1. Are patients with advanced lung disease able to tolerate semaglutide therapy? 2. Are we able to titrate semaglutide therapy to a target weight? Participants will be asked to perform pulmonary function, physical function and body composition testing, as well as a blood draw before and after 12-weeks of semaglutide therapy. While on therapy, subjects will be surveyed regarding any adverse events or side effects.
The purpose of this study is to investigate the role of the oral JAK1 inhibitor, abrocitinib 200 mg once daily, for the treatment of patients with moderate to severe cutaneous sarcoidosis.