The primary purpose of conducting this study is to see if TLD (Targeted Lung Denervation) Therapy in addition to standard optimal medical care is better at reducing a moderate or severe exacerbation (also known as a COPD flare-ups or worsening of symptoms) and related hospitalizations than optimal medical care alone. TLD Therapy is done by passing a bronchoscope, with a special device (catheter) inserted through it, into the lungs. This special catheter delivers a type of electrical energy called radiofrequency (or RF) energy to the nerves located on the outside of the airways. As with many bronchoscopic procedures, this is done while under anesthesia. TLD Therapy does cause a permanent change to a person's lungs. To test this, participating patients will be randomly assigned (in a 1:1 ratio) to receive one of two different treatments, either TLD Therapy in addition to optimal medical care or optimal medical care alone.
Some sites, including MUSC, will also be collecting 3 airway brushes to look at inflammatory biomarkers in the lungs. A biomarker is anything that can be used as an indicator of a particular disease state.
If you choose to participate in this study, it is estimated that you will be involved in this study for approximately 62 months. Participation will take around 11 clinical site visits and 9 follow up phones calls over a period of 5 years. The participant and person obtaining consent will sign the informed consent form and the participant will receive a copy before any study procedures occure.
Alpha-1 antitrypsin (Alpha-1, AAT) deficiency is an inherited disease which results from a defect in the alpha-1 gene. Severe AAT deficiency causes emphysema predominant chronic obstructive pulmonary disease (COPD). This study is designed to test the effectiveness of an drug (Alvelestat) on lung damage caused by Alpha-1 Antitrypsin Deficiency. This is blinded study and there is a 50% chance of receiving a placebo.
Alpha-1 Antitrypsin (AAT) is a naturally occurring protein involved in the protection of lungs from inflammation. A mutation in the AAT gene (a change in the body's genetic instructions on how to make AAT) causes it to be made incorrectly and very little of it gets into the bloodstream.This results
in the lung damage known as emphysema. ARO-AAT is an investigational drug, which means that it is not approved by the Food and Drug Administration. ARO-AAT works by interrupting a step in the production of AAT. In a patient with AATD, this would stop the mutated protein from being made. This study is being carried out to see how safe and well tolerated ARO-AAT is, and to see if low, medium and high doses of the study treatment will decrease Alpha-1 Antitrypsin in the blood and in the liver compared to a placebo, or dummy injection. The Study medication is given via injection on Day 1, 29 and 133 and then every 84 days. The study includes approximately 17 visits over a period of 24 month. Compensation will be provided for study site visits. .
This study is designed to follow individuals who participated in "Phase 1/2 Study of Intravenous or Intrapleural Administration of a Serotype rh.10 Replication Deficient Adeno-associated Virus Gene Transfer Vector Expressing the Human Alpha-1 Antitrypsin cDNA to Individuals with Alpha-1 Antitrypsin Deficiency" for 5 years after receiving treatment.
Lymphangioleiomyomatosis (LAM) is a rare lung disease that is caused by genetic mutations. It results in the uncontrolled growth and proliferation of an atypical smooth muscle cells in the lung. These cells invade airways, blood vessels, and lymph vessels, and limit the flow of air, blood, and lymph, respectively. The source of the cells is unknown, but available evidence indicates they arise from an extrapulmonary source. Their aberrant behavior is due to mutations in tuberous sclerosis genes that results in mTOR activation. Respiratory failure, lung collapse (pneumothorax), and pleural effusions (chylothorax) are hallmarks of the disease. This study will evaluate the safety and durability of the mTOR inhibitors sirolimus and everolimus, which are FDA approved medications for prevention of rejection of transplanted organs, in stabilizing or improving lung function in people in LAM.
Individuals with a confirmed diagnosis of alpha-1 antitrypsin (AAT) deficiency and emphysema will be invited to participate in this study. This study will determine the safety and effectiveness of Inhaled Hyaluronic Acid solution as a possible treatment of emphysema in AATD patients. A participant in this study will be asked to inhale the study medication or a placebo delivered by a nebulizer twice a day for 28 days. Neither the study investigators nor the participant will know if they are receiving active drug or placebo. Safety and side effects of all therapies will be monitored.
Individuals with alpha-1 antitrypsin (AAT) deficiency (AAT blood level lower than 11 micro-moles) and emphysema will be invited to participate in this study. This study will determine the impact of IV Alpha-1 proteinase inhibitor (Alpha-1 MP) on the progression of emphysema in patients with AAT deficiency. A participant in this study would receive either GLASSIA dosed at 60mg/kg with a high particle load or GLASSIA dosed at 60mg/kg with a low particle load. Neither the study investigators nor the participants will know which batch of drug is actual given to the participant. Participants will have the IV therapies given to them weekly for 25 weeks, with some infusions given at MUSC and some at home. Safety and side effects of all therapies will be monitored.
The purpose of the Alpha-1 Foundation Clinical Resource Center (CRC) Research Registry is to collect and store medical information from individuals with alpha-1 antitrypsin deficiency (AATD or Alpha-1) or individuals that carry a deficient Alpha-1 gene. The Registry will collect medical information on your disease and diagnosis. This information will include family history, lung and liver symptoms, and exposure to cigarette smoke, dusts and fumes.The goal of this project is to obtain and share information that defines the natural history of alpha-1 antitrypsin deficiency. Biological samples from either blood or tissue may be collected and stored as part of this research. This project will assemble a library of these biological samples, some of which will be saved at MUSC.
Alpha-1 Antitrypsin Deficiency (Alpha-1) is a hereditary condition that is passed on from parents to their children through genes. This condition may result in serious lung disease in adults and/or liver disease in infants, children and adults.
Alpha-1 occurs when there is a severe lack of a protein in the blood called alpha-1 antitrypsin (AAT) that is mainly produced by the liver. The main function of AAT is to protect the lungs from inflammation caused by infection and inhaled irritants such as tobacco smoke.
The low level of AAT in the blood occurs because the AAT is abnormal and cannot be released from the liver at the normal rate. This leads to a build up of abnormal AAT in the liver that can cause liver disease. Finding out the test results early may affect the onset and progression of the disease.
The Alpha-1 Coded Testing (ACT) Study offers free and confidential finger stick testing for Alpha-1 Antitrypsin Deficiency. The test can be completed at home and results are mailed to the participant's home. This test is available through a research study, the Alpha-1 Coded Testing (ACT) Study. The Study investigates people's thoughts and feelings about the risks and benefits associated with learning genetic information. Anyone over age 18 can request to be tested. Participants or the participant's guardian must sign a consent form, fill in a questionnaire, and allow for recontact in the future. Full details are available in the consent form.