Clinical Research Directory

GRAfT 2.0. A Multimodal Prospective Approach to Define the Mechanisms and Clinical Features of Acute and Chronic Rejection in Lung Transplantation

Background: Lung transplants can save lives, but the procedure has risks. Some people develop donor-specific antibodies (DSA) after the procedure-that is, their bodies create proteins that treat the new lungs as foreign and mount an immune response against them. This is called rejection. But not everyone who has a transplant develops DSA, and not everyone who has DSA develops rejection. Researchers want to understand why. Objective: To collect data to try to find out why some people develop rejection after lung transplants while others do not. Eligibility: People aged 18 to 75 years who have undergone or may undergo a lung transplant. Design: Participants will have clinic visits every 3 to 6 months for up to 4 years. Some visits might require an overnight stay. Each visit will include multiple tests and procedures: Physical exam with blood and urine tests. Some blood will be used for genetic testing. Imaging scans. Participants will have 2 types of scan to get images of their lungs. For one, they will have a contrast agent given through a tube inserted into a vein. Six-minute walk test. Participants will walk back and forth in a hallway at their own pace. Researchers will check on how their body responds. Lung function test. Participants will breathe into a tube connected to a machine. Two other tests are optional: Bronchoscopy with washings (lavage). A long tube with a light will be threaded down through the participant s nose or mouth and into their lungs. Endomicroscopy. During the bronchoscopy a tiny camera may be used to take pictures inside the lungs.

Pre-transplant Health Coaching to Improve Patient-Reported Outcomes in Lung Transplant Candidates

To examine the effectiveness of an individual health coaching intervention for lung transplant candidates. This intervention will include up to 12 health coaching sessions via phone call over a 12-16 week period. This will be compared to a usual care group the receives pre-transplant care and education alone.

Bridge to Lung Transplant With Trans-septal Extra-corporeal Membrane Oxygenation (ECMO) for Right Heart Failure From Pulmonary Hypertension

The purpose of this study is to determine if transseptal extra-corporeal membrane oxygenation (ECMO) can bridge pulmonary hypertension- right heart failure (PH-RVF) patients to lung transplant safely.

Tocilizumab in Lung Transplantation

This is a trial in which 350 primary lung transplant recipients will be randomized (1:1) to receive either Tocilizumab (six doses over 20 weeks) plus standard triple maintenance immunosuppression or placebo (sterile normal saline) plus standard triple maintenance immunosuppression (Tacrolimus, Mycophenolate Mofetil, corticosteroids). The primary objective is to test the hypothesis that treatment with triple maintenance immunosuppression plus Tocilizumab (TCZ) is superior to triple maintenance immunosuppression plus placebo (saline) as defined by a composite endpoint of a) CLAD, b) listed for re-transplantation, and c) death

10°C vs 4°C Lung Preservation RCT

Despite lung transplantation (LTx) being the most effective treatment for end-stage lung disease, its success rate is lower than that of other solid organ transplantations. Primary graft dysfunction (PGD) is the most common post-operative complication and a major factor in early mortality and morbidity, affecting \~25% of lung transplant patients. Induced by ischemia reperfusion, PGD represents a severe and acute lung injury that occurs within the first 72 hours after transplantation, and has a significant impact on short- and long-term outcomes, and a significant increase in treatment costs. Any intervention that reduces the risk of PGD will lead to major improvements in short- and long-term transplant outcomes and health care systems. One of the main strategies to reduce the risk and severity of post-transplant PGD is to improve pre-transplant donor lung preservation methods. In current practice, lung preservation is typically performed by cold flushing the organ with a specialized preservation solution, followed by subsequent hypothermic storage on ice (\~4°C). This method continues to be used and applied across different organ systems due to its simplicity and low cost. Using this method for the preservation of donor lungs, the current maximum accepted preservation times have been limited to approximately 6-8h. While the goal of hypothermic storage is to sustain cellular viability during ischemic time through reduced cellular metabolism, lower organ temperature has also been shown to progressively favor mitochondrial dysfunction. Therefore, the ideal temperature for donor organ preservation remains to be defined and should maintain a balance between avoidance of mitochondrial dysfunction and prevention of cellular exhaustion. In addition to that, safe and longer preservation times can lead to multiple advantages such as moving overnight transplants to daytime, more flexibility to transplant logistics, more time for proper donor to recipient matching etc. Building on pre-clinical research suggesting that 10°C may be the optimal lung storage temperature, a prospective, multi-center, non-randomized clinical trial was conducted at University Health Network, Medical University of Vienna and Puerta de Hierro Majadahonda University Hospital. Donor lungs meeting criteria for direct transplantation and with cross clamp times between 6:00pm - 4:00am were intentionally delayed to an earliest allowed start time of 6:00am and a maximum preservation time from donor cold flush to recipient anesthesia start time of 12 hours. Lungs were retrieved and transported in the usual fashion using a cooler with ice and transferred to a 10°C temperature-controlled cooler upon arrival to transplant hospital until implantation. The primary outcome of this study was incidence of Primary Graft Dysfunction (PGD) Grade 3 at 72h, with secondary endpoints including: recipient time on the ventilator, ICU Length of Stay (LOS), hospital LOS, 30-day survival and lung function at 1-year. Outcomes were compared to a contemporaneous conventionally transplanted recipient cohort using propensity score matching at a 1:2 ratio. 70 patients were included in the study arm. Post-transplant outcomes were comparable between the two groups for up to 1 year. Thus, intentional prolongation of donor lung preservation at 10°C was shown to be clinically safe and feasible. In the current study design, the investigators will conduct a multi-centre, non-inferiority, randomized, controlled trial of 300 participants to compare donor lung preservation from the time of explant to implant at \~10°C in X°Port Lung Transport Device (Traferox Technologies Inc.) vs a standard ice cooler. When eligible donor lungs become available for a consented recipient, the lungs will be randomized to undergo a preservation protocol using either 10°C (X°Port Lung Transport Device, Traferox Technologies Inc.) or standard of care. The primary outcome of the study is incidence of ISHLT Primary Graft Dysfunction Grade 3 at 72 hours. Post-transplant outcomes will be followed for one year.

Belumosudil to Block Chronic Lung Allograft Dysfunction (CLAD) in High Risk Lung Transplant Recipients

The purpose of this study is to see if taking the study drug, Belumosudil, for 52 weeks in addition to your usual care and medication, will prevent Chronic Lung Allograft Dysfunction (CLAD) in participants who have a lung biopsy that shows evidence of rejection or inflammation to the transplanted lung(s). For this study, biopsies that show evidence of Acute Rejection (AR), Lymphocytic Bronchiolitis (LB), Organizing Pneumonia (OP) or Acute Lung Injury (ALI) are referred to as "Qualifying Biopsies"; patients who had evidence of one or more of these conditions on a recent biopsy are eligible for enrollment in this study. Belumosudil is an investigational drug that blocks a molecule in the body that reduces inflammation and scarring and may play a role in the development and progression of CLAD. Belumosudil is a drug approved by the FDA to treat adults and children 12 years and older with chronic graft-versus-host disease (cGVHD), a condition with some similarities to CLAD. The primary objective it to determine the efficacy of treatment with Belumosudil + maintenance immunosuppression (IS) versus placebo + maintenance IS on preventing the subsequent development of probable or definite CLAD, lung retransplant, or death.

Thoracic Specimen Registry

The purpose of the registry will be to support ongoing research in the etiology, early diagnosis, clinical management, and prognosis of lung cancer and other cancers and diseases of the thorax by developing a complete repository of specimens from patients with thoracic disease including but not limited to suspected lung cancer, mediastinal and pleural tumors, lung transplants and from patients at a very high risk of developing other thoracic cancers or other thoracic diseases.

Decreasing Edema With a Novel OCS Solution Trial

This is a prospective, multicenter randomized trial of lung transplant recipients transplanted with either a DBD or DCD donor lungs. The DENOVO Trial will enroll a total of 300 patients in the OCS arm and 150 patients in the SCS arm. The primary endpoint will be patient \& graft survival and freedom of Primary Graft Dysfunction (PGD) grade 3 within the initial 72 hours post-transplantation.

Protest Trial: TXA vs Saline

To determine if endobronchial (topical) tranexamic acid used prophylactically prior to performing transbronchial biopsies in lung transplant recipients reduces bleeding risk.

A Study of Latin Dance for Post- Lung Transplant

The purpose of this research study is to see if participating in Latin dance for 12 sessions can improve wellbeing in several areas including balance, fear of movement, anxiety, depression and spirometry.

US National TOP Registry

The objective of this Registry is to collect short and long-term post-transplant clinical outcome data of all donor lungs preserved and assessed on the OCS Lung System and to document the performance of the OCS device in the real-world setting after FDA approval in the US.

TEE and Dysphagia in Lung Transplantation

The primary outcome of this study is dysphagia (difficulty swallowing) on postoperative speech and swallow evaluation following lung transplantation. Transesophageal echocardiography (TEE) (creates pictures of the heart from inside the participants body) is routinely performed for all lung transplantations at the University of California, Los Angeles (UCLA) and it is the standard of care. Patients are randomized to two groups. The intervention group would limit the number of TEE clips (# pictures taken) per case. The control group would leave the number of TEE clips to the discretion of the attending anesthesiologist. The investigators hypothesize that reduction in TEE imaging during lung transplantation will reduce dysphagia.

The Effect of the Reflux Band™ Upper Esophageal Sphincter (UES) Assist Device on Reflux for Lung Transplant Recipients

A prospective, open label, study designed to assess the affect of the Reflux Band® UES Assist Device (Reflux Band) on reflux in patients that have undergone lung transplantation.

Bronchial Response to Exercise After Double Lung Transplantation

This study aims to investigate the airway response to exercise and its association with breathlessness in double lung transplant recipients by comparing responses during 5-minute and 15-minute exercise durations.

A Study of Venoarterial ECMO vs Off-Pump Bilateral Orthotopic Lung Transplantation

The purpose of this research study is to compare the technique of performing bilateral lung transplantation off-pump vs venoarterial ECMO (VA ECMO). The goal of the trial is to determine which technique has lower rates of primary graft dysfunction.

A2 to O Lung Transplants

Blood group A2 to blood group O kidney and liver transplants have been shown to be safe and successful, especially in recipients with low pre-operative anti-A antibody titers and with the use of peri-operative antibody-depleting therapies. Since blood group O lung transplant candidates tend to have longer wait times and a higher waitlist mortality compared to other blood groups, we propose to conduct a prospective study of lung transplantation from blood group A2 donors to eligible blood group O recipients in an effort to increase the available donor pool. The aim of this study is to determine both the feasibility and safety of this specific type of ABO-incompatible lung transplant, and the impact of this practice on reducing transplant wait times among blood group O lung transplant candidates. This would represent the first prospective study of ABO-incompatible lung transplants worldwide.

DREAM: Double Lung Transplant REgistry Aimed for Lung-limited Malignancies

This is a prospective observational registration trial for patients who undergo lung transplantation for the treatment of the select groups of medically refractory cancers affecting the lungs alone without extrapulmonary nodal and distant metastasis.

The Effect of Nutrition and BMI on on Lung Capacity, Functional Capacity and Mortality in End-Stage Lung Patients

The aim of this study was to investigate the effect of nutritional risk index, BMI and body fat, muscle ratio on functional capacity, lung capacity, exercise capacity index, all-cause mortality, post-transplant intensive care unit stay and survival time in end-stage lung patients on the lung transplant list.

Progressive Rehabilitation Therapy in Patients With Advanced Lung Disease

The International Society of Heart and Lung Transplantation Registry data shows that there is a growing population of critically ill patients with advanced lung disease undergoing lung transplantation. The goal of our study is to evaluate the role of intensive physical therapy for patients with advanced lung disease requiring transplant or ECMO(extracorporeal membrane oxygenation)- bridge to transplant with emphasis on the restoration of functional independence and prevention of functional declines after lung transplantation. The project is a designed as a randomized prospective research study investigating the impact of a multi-modal rehabilitation program(MRP), which incorporates neuromuscular electric stimulation(NMES), strength and mobility training, and nutritional supplementation(NS) in ameliorating the loss of muscle mass and strength, and lower extremity balance, strength and coordination that will decrease time on the ventilator or ECMO, stay in the ICU and hospital.

An All Comers Registry For Normothermic Ex Vivo Lung Perfusion (EVLP) as Assessment of Donor Lungs for Transplant

The XVIVO Registry is to collect standard of care clinical data from "all-comers" who are transplanted with an EVLP lung treated with the XVIVO Perfusion System™ in order to assess the long-term performance of the device, and monitor device-related serious adverse events. In addition, 4 and 5-year UNOS registry data of the 126 subjects who received an EVLP transplant under the NOVEL and NOVEL Extension studies are provided as part of the long-term safety and quality of life data. In addition, 4 and 5-year UNOS registry data of the 126 subjects who received an EVLP transplant under the NOVEL and NOVEL Extension studies are provided as part of the long-term safety and quality of life data.