The purpose of this study is to create a de-identified, public use,
repository of data of Chronic Obstructive Pulmonary Disease (COPD)
patients with by Alpha-1 antitrypsin deficiency (AATD), a rare genetic
condition that can cause COPD and emphysema.

This Phase 2b study is a randomized, double-blind, parallel-arm, placebo-controlled trial to evaluate safety and efficacy of Saroglitazar Magnesium 2 mg and Saroglitazar Magnesium 4 mg compared with placebo in subjects with NASH. Subjects will be randomized 1:1:1 to receive Saroglitazar Magnesium 4 mg, Saroglitazar Magnesium 2 mg, or placebo via IVRS/IWRS. Total duration of the study will be up to 89 weeks including two screening visits (12 weeks), randomization and double-blind treatment phase (76 weeks), and a safety follow-up of 1 week after the last administration of study drug. Subjects will be evaluated at the study site for 14 scheduled visits. During the course of the study subjects will have 2 liver biopsies and 6 transient elastography/FibroScan performed to monitor liver fibrosis.

The primary purpose of this registry is to evaluate the feasibility and clinical validation of LiverCare in liver transplant recipients, as part of post-transplant surveillance. LiverCare is an investigational panel test that includes 6 components: 1. AlloSure Liver 2. AlloMap Liver 3. AlloHeme Liver 4. iBox Liver 5. HistoMap Liver 6. AlloID. AlloSure Liver is a research test used to measure donor-derived cell free DNA in Liver transplant recipients. AlloMap Liver is a research gene expression profile test using peripheral blood to establish immune activity and is currently undergoing clinical evaluation and development. iBox Liver is an analytic platform that predicts organ outcomes after transplant using a software algorithm based on information from your medical records and is currently undergoing clinical evaluation and development. AlloHeme Liver is a diagnostic test to measure donor and recipient DNA in the blood. HistoMap Liver is a tissue-based gene expression test using tissue collected from standard of care biopsies to establish immune profiles within the organ and is currently undergoing clinical evaluation and development. AlloID is a blood test that will quantify the presence of more than 100 pathogens including standard post-transplant infectious disease screening such as Cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, Human Herpesvirus 6 (HHV-6) and viral hepatitis.

The purpose of this study is to find out about the safety and effectiveness of an investigation drug called Semaglutide for the treatment of NASH. (Non-Alcoholic Steatohepatitis). NASH occurs when the fat buildup in the liver leads to inflammation (hepatitis) and scarring. NASH is associated with increased risk of morbidity (medical problem or complication) and mortality (death). Currently, treatment options are few and insufficient. There is therefore an unmet medical need for effective and safe pharmacological treatment options. The study is designed to last 257 weeks (approximately 4 years and 11 months), with study visits occurring approximately every 4 weeks. Most visits will include blood work and some will include assessments such as body weight and vital signs. Most visits will include reviewing of diary entries during the course of the study. This study also includes weekly injections of semaglutide (or placebo). Semaglutide is a self-administered injection that is given under the skin. Semaglutide has built an extensive amount of data with other trials that have focused on weight management and Type 2 diabetes. Semaglutide is FDA-approved for diabetes treatment, but is investigational for this study. In these previous trials, semaglutide was found to be safe and well-tolerated. This study is randomized, double-blinded, and placebo-controlled. This means that you may receive the study drug or a placebo. Neither the study subject or the study team members will know which each subject will be receiving. Study subjects will be randomized 2:1. This means that subjects will have a greater chance (66%) of receiving the drug versus the placebo.

This is a two armed multicenter cluster randomized controlled trial (RCT), to assess the effectiveness of two pragmatic PC models for patients with ESLD (Consultative PC vs. Trained hepatologist led PC). To prevent bias at the level of providers, randomization will take place at the level of clinical centers; however patients will be the unit of inference. Parallel to this cluster-RCT, a qualitative study will be undertaken to evaluate the patient/caregiver experiences in the two PC models, using semi structured interviews.

To execute this project, Duke has identified 19 clinical centers to participate; 8 Veterans Health Administration (VHA) systems and 11 non-VHA, Academic Medical Centers.

Comparative Approaches:
1.Consultative PC led approach (Model 1): The PC model will include: 1) routine PC consults, using a standardized checklist , 2) in-person visits at initial, 1 and 3 months.
2.Trained hepatologist led PC (Model 2): The Hepatologist Led PC model will comprise: 1) Hepatologist training (through E Learning modules), and 2) in person visits utilizing the same PC checklist as utilized in Model 1. The in-person visits will occur at initial, 1 and 3 months i.e. similar to Model 1 and follow the same visit specified agenda.

MUSC has been assigned to the Model 2 approach, "Hepatologist led Palliative Care" to be lead by Dr. Don Rockey and Dr. Heather Simpson.

Adult patients 18 years of age or older will be enrolled. With 14 clinical centers in different geographic locations and diversity in race/ ethnicity, 1260 patient/ caregiver dyads will be enrolled.

The purpose of the MUSC Pulmonary Biorepository is to collect and store samples linked to medical and other information from individuals with pulmonary disease as well as healthy controls.

In combination with the clinical data and other approved research studies (that may recruit for and/or utilize samples of the biorepository) this sample repository will provide for uniform, longitudinal, complete and accurate data that can be organized and clinically correlated at the time of sample donation, with longitudinal testing possible as part of future study. Samples will be linked to each participant's unique ID, though will be deidentified and coded for use in future research and subsequent publications with pulmonary disease and control patients.