View clinical trials related to Alpha 1-Antitrypsin Deficiency.
Filter by:This is a multicenter, randomized, partial-blinded, five-arm, placebo-controlled study of human plasma-derived alpha1-proteinase inhibitor (alpha1-PI) in children (ages 6-11 years old) and teens/adults (ages 12-35 years old) with new onset Type 1 Diabetes Mellitus (T1DM). Currently enrolling ages 12-35 only. Once 25 patients are randomized and data is reviewed enrollment will be opened to the child cohort. The purpose of this study is to evaluate the safety and efficacy of four dosing regimens of human plasma-derived alpha1-PI in T1DM.
The investigators hypothesize that there is liver injury (inflammation, fibrosis, cirrhosis) in adults with Alpha-1 Antitrypsin Deficiency (AATD), which is asymptomatic, under-recognized, and undiagnosed. In addition, the investigators believe that the genetic and environmental factors that play an important role in the development of alpha-1 antitrypsin (AAT) liver disease, can be identified by comparing a cohort database of clinical disease information to linked biospecimen and DNA samples.
To evaluate different doses of "Kamada-AAT for Inhalation" on the levels of alpha 1-proteinase inhibitor and other analytes in epithelial lining fluid (ELF) and serum and to assess the safety of the treatment in subjects with AAT Deficiency.
This is a multi-center, randomized, placebo-controlled, double blind clinical study to assess the efficacy and safety of two separate dose regimens of Alpha-1 MP versus placebo for 156 weeks (i.e., 3 years) using computed tomography (CT) of the lungs as the main measure of efficacy. The two Alpha-1 MP doses to be tested are 60 mg/kg and 120 mg/kg administered weekly by IV infusion for 156 weeks. The study consists of an optional pre-screening phase, Screening Phase, a 156-week Treatment Phase, and an End of Study Visit at Week 160.
This is a longitudinal, observational, non-interventional registry study, designed to collect both retrospective and prospective real world data, on patients receiving Alpha-1 augmentation therapy in the home through Coram Specialty Infusion.The data will be collected from standard Coram homecare forms, as well as patient reported case forms.
The deficiency of alpha-1 antitrypsin (DA1AT) is a genetic disorder of variable clinical expression, initially described in adults with pulmonary emphysema patients. In children, it is the second cause of neonatal cholestasis after biliary atresia and is a common indication for liver transplantation. Several genotypes for SERPINA1 gene coding for alpha-1 anti-trypsin were identified. The main ones are M / M, M / Z, M / S and Z / Z and each genotype is closely correlated with the concentration of blood A1AT. The estimate for France suggests a prevalence of genotype deficit Z / Z of the order of 1/6054, (9982 patients), which in 11% of cases, have liver disease (prolonged neonatal jaundice). Half of them will move towards the development of cirrhosis with portal hypertension, at worst liver transplantation. Currently, we do not know what are the clinical and genetic factors that predispose a patient A1AT deficiency develop liver damage. Recent studies have led us to think that polymorphisms in the gene SERPINA1, as well as that of the alpha-mannosidase 1 endoplasmic reticulum (Erman gene) could be a predictive marker of liver complications. Another possible candidate gene is one of the importin beta (KPNB1), a protein involved in the elimination of misfolded proteins. These data lead us to propose the study of genetic polymorphisms. The main objective of the study is to compare the allele frequencies of these polymorphisms between (i) a cohort of A1AT deficient patients and with hepatic symptoms (portal hypertension and its complications, severe liver failure leading to transplant or not, or an indication for liver transplantation) and (ii) a cohort of A1AT deficient patients without signs of hepatic call. To build this last cohort, we will include in the genetic study the family members of deficient patients, some of whom probably carrying a deficit genotype Z / Z but without any associated clinical manifestations. This will allow us to facilitate the establishment of genotype profiles / phenotype clearly identified, which then allow a more appropriate care for children who may have such a development, we will strive to achieve a haplotype interpretation of polymorphisms found. This study will be conducted in association with the DEFI-ALPHA study to identify clinical and biological prognostic factors such as age at diagnosis, the diagnostic mode, the results of liver biopsy (when available), the clinical course, family history, the existence of IUGR and long-term treatment. The secondary objectives of the study are : - The measurement and interpretation of serum IL-8 in A1AT-deficient patients. Indeed, one study showed a higher IL-8 in patients with ulcerative colitis compared with healthy patients' serum. These considerations led us to hypothesize that IL-8 may be a marker of liver disease in A1AT deficiency. - Preservation of blood samples for further study of other genes, which may be in the future suspected to be associated with the occurrence of liver complications. To this end, a DNA bank will be created. It will involve the children with a deficiency of alpha-1 antitrypsin and their family of 1st and 2nd degree in civil law (parents and siblings). This study is a continuation of the cohort DEFI-ALPHA (descriptive study of a cohort of children with DA1AT) and sought to identify the clinical and biological factors such as age at diagnosis, diagnosis mode, the result sets of the liver biopsy (when available), clinical course, family history, the presence of IUGR and long-term treatment. The only criterion for not-inclusion is, according to the subject, the lack of consent of the child and his parents, the lack of consent of the adult patient, or the lack of consent of the witness. Demographic and clinical history data (for parents and brothers/sisters showing no DA1AT) will be collected. Currently, the cohort of patients with DA1AT is being set up in the framework of the "Cohort DEFI-ALPHA." This multicenter project is realized with the help of french pediatric hepatology centers that regularly follow patients DA1AT. Today, over 100 patients DA1AT have already been identified, and the collection of historical data has already begun on several centers since September 2009. This study is therefore a continuation of this work. Over a period of 30 months, the total number of potentially includable subjects is estimated at about 400 in this study (100 patients and 300 related to the first degree such as parents, brothers and sisters). This study will be promoted by the Hospices Civils de Lyon. Authorization of the competent authority and the ethical committee will be obtained as well as informed consent from families before blood sampling.
The purpose of this study is to look at how Alpha-1-antitrypsin (AAT) deficiency and Cystic Fibrosis (CF) affect white blood cells in the lungs, called macrophages, and their ability to work.
This project is designed to examine the interaction between the microflora in the lower airway and the concentration of a serum protein called alpha-1 antitrypsin. The hypothesis is that alpha-1 antitrypsin impacts the diversity and content of the lower airway microflora, resulting in a less inflammatory airway. The Specific Aims are: 1. To compare the lower respiratory tract microbiome and virome population diversity and content in age and GOLD stage matched PiZZ individuals not receiving augmentation therapy, PiZZ individuals on augmentation therapy, PiMZ individuals not receiving augmentation therapy, and PiMM individuals with chronic obstructive pulmonary disease (COPD). 2. Determine correlations between bronchoalveolar lavage (BAL) and peripheral blood gene expression patterns and patterns in lung microbial and viral populations across all cohorts. 3. Correlate the presence or absence of computed tomography (CT) bronchiectasis and bronchiolectasis with patterns in the microbiome population diversity and content. 4. To identify and define novel molecular phenotypes of Alpha-1 Antitrypsin Deficiency (AATD) based on computational integration of clinical, transcriptomic, and microbiome data.
This project is designed to address the following hypothesis: Distinct patterns in lung microbiome are characteristic of sarcoidosis phenotypes and reflected in changes in systemic inflammatory responses as measured by peripheral changes in gene transcription. The Specific Aims are: 1. To identify peripheral blood mononuclear cell (PBMC) gene expression patterns that characterize distinct sarcoidosis phenotypes. 2. To determine whether patterns in the lung microbiome are associated with sarcoidosis severity and disease phenotypes 3. To correlate mRNA and microRNA expression patterns in sarcoidosis affected organs with changes in microbiome, clinical parameters and PBMC gene expression patterns 4. To integrate clinical, transcriptomic, and microbiome data to identify novel molecular phenotypes in sarcoidosis.
We hypothesize that individuals with Alpha-1 Antitrypsin (AAT) deficiency have ongoing liver injury which is not detected by the usual blood tests used to look at liver function. This ongoing liver injury leads to cirrhosis in a significant number of adults with AAT deficiency.