29 Clinical Trials for Various Conditions
This study will explore the ways in which lung transplants are rejected. A series of experiments will evaluate the differences in airway gene expression. Lung transplantation has become an important option for patients with advanced lung disease. More than 10,000 patients have received them to date, and about 1,200 transplant operations are performed worldwide each year. Although short-term survival has continued to improve, the 5-year survival rate is less than 50%. Most posttransplant deaths are directly or directly caused by chronic lung rejection, a condition of scarring that worsens lung function. . Patients ages 18 and older who have received lung transplants, who are undergoing bronchoscopy as part of the usual care after transplant, and who are not pregnant may be eligible for this study. Bronchoscopy and other procedures performed during this study are done only by doctors with special training. They will take a total of 30 to 60 minutes. During a bronchoscopy, patients will lie on a flat bed. They will be awake and follow instructions. First they will breathe Xylocaine (lidocaine), an anesthetic mist, for 8 to 10 minutes. That will lessen the discomfort of a small flexible tube called a bronchoscope that will be guided through the back of the patient's mouth or nose and into the breathing tubes. When the flexible tube is placed, patients will not be able to speak. They will receive the medication Versed (midazolam), to make them relaxed and not remember most of the procedure, and fentanyl, to decrease the possibility of feeling pain. These medications will be given through a narrow tube feeding into a small needle placed into a vein in the arm. The risks of the tube placed in the vein include bleeding, swelling, redness, and pain. Side effects from the medications may include stomach upset, heart palpitations (awareness of heartbeat), and changes in blood pressure. Patients will be carefully monitored for heart rate, blood pressure, breathing, and oxygen levels. During the bronchoscopy, a procedure called bronchoalveolar lavage is done, in which a small amount of germ-free salt water is injected into through the bronchoscope into the lung and immediately suctioned back, thus washing the lining of the airways and checking for infection and rejection of the transplanted lungs. About 1 or 2 tablespoons of fluid will be collected for analysis. Also, an endobronchial brush biopsy may be performed. A small brush removes some of the cells from the surface of the airway. These cells will be sent to a laboratory at Duke University Health system to analyze the signals from the cells that may eventually led to scarring and chronic rejection of the lungs. Then, an endobronchial forceps biopsy is performed, in which one or two small pieces, each about the size of a grain of rice, of the lining of the lung's large airways is removed. A small surgical tool like tweezers is passed into the lung. Risks of biopsies may include bleeding, injury to the lung, or an air leak in the lung. This study will not have a direct benefit for participants. However, it is hoped that information gathered will enhance researchers' understanding of how lung rejection occurs.
Doctors have had success preventing certain types of kidney transplant rejection by suppressing the immune system. However, an individual's genetic make-up and the strength of an immune response to a transplant may also determine whether a transplanted organ is rejected. The purpose of this study is to look at the genetic profile and immune response of people who have had kidney transplants and to correlate the findings with kidney transplant rejection episodes. Donor genetic profiles will also be studied and correlated with the recipient's information.
The purpose of this study is to help researchers find out more about a condition called "Chronic Allograft Nephropathy" (CAN). CAN is a complication that sometimes occurs after kidney transplantation and affects the function of the transplanted kidney. It is hoped that by studying blood, urine, and tissue samples of kidney transplant patients, new ways of diagnosing and treating CAN may be found.
The purpose of this study is to assess the efficacy and safety of the study drug, known as "ATG Fresenius S," which is sometimes called "EZ-2053," to prevent a lung transplant patient's body from rejecting a transplanted lung or lungs.
This study is intended to help doctors learn about the relationships between specific genetic makeup (gene markers) and the development of chronic rejection. This study is being done to see if there is a relationship between genetic patterns and the development of Chronic Allograft Nephropathy (CAN). Medical scientists also hope to learn more about how genetic differences between people determine their response to a drug or a disease by storing a small blood sample in a special "bank". This sample may be tested at some point in the future in an attempt to better understand the factors that may influence rejection, transplantation outcomes and transplant success rates.
The purpose of this study is to see how effective 2 drugs, irbesartan and pravastatin, are at slowing kidney transplant failure. Many kidney transplant patients have some type of chronic rejection. Chronic rejection is a disease that causes scarring and damage to the kidney. Over time, chronic rejection can lead to kidney failure, making it necessary for patients to start dialysis and possibly receive another kidney transplant. Doctors would like to see whether irbesartan and pravastatin can slow this damage and prevent kidney failure in patients with signs of chronic rejection.
Chronic Allograft Nephropathy (CAN)/Interstitial fibrosis and Tubular Atrophy (IFTA) is responsible for most kidney transplant failures. CAN/IFTA on a 3 month kidney biopsy strongly predicts graft survival long term. CAN/IFTA remains a vexing problem for clinicians because current monitoring tools, namely the serum creatinine concentration, are not sensitive to early changes in glomerular filtration rate (GFR) or to histologic damage. Despite advances in prevention of acute rejection (AR), it is still a significant and potentially devastating complication of solid organ transplantation. One strategy to reduce the risk of rejection is to perform kidney biopsies to detect subclinical acute rejection (SCAR) and treat to prevent progression to rejection. There is evidence that treating SCAR can prevent further immune mediated injury to the kidney, a precursor to CAN/IFTA. Kidney biopsies provide better information but are limited due to safety concerns, patient preference and cost issues. Better, early and less invasive markers of CAN/IFTA will allow early intervention as well as improved graft and better patient outcomes. This study seeks to validate specific proteogenomic biomarker panels for AR and CAN/IFTA in a prospective blood, urine and kidney tissue monitoring study of kidney transplant recipients who will be scheduled for standard of care biopsies.
Hyperparathyroidism (HPT) is common in people with a kidney transplant. Patients with HPT often have high parathyroid hormone (PTH) levels and may have large parathyroid glands in the neck. Patients with HPT can develop bone disease (osteodystrophy). This bone disease can cause bone pain, fractures, and poor formation of red blood cells. Other problems from HPT may include increases in blood levels of calcium (hypercalcemia) and low blood levels of phosphorus (hypophosphatemia). The high calcium levels may cause calcium to deposit in body tissues. Calcium deposits can cause arthritis (joint pain and swelling), muscle inflammation, itching, gangrene (death of soft tissue), heart and lung problems or kidney transplant dysfunction (worsening of kidney transplant function). The purpose of this study is to evaluate the effects of cinacalcet (Sensipar/Mimpara) on high calcium levels in the blood in patients with HPT after a kidney transplant.
There is a need to develop blood and/or urine tests that will help to detect early signs of rejection in people who have had kidney transplant. Researchers will examine blood, urine, and tissue samples and try to identify genetic markers for certain conditions like rejection, response to therapy, and scarring of the kidney. By studying gene patterns, researchers hope to be able to diagnose these conditions earlier and improve kidney survival.
The objective of this study is to evaluate the safety and efficacy of conversion from tacrolimus to sirolimus early after kidney transplantation in patients with delayed graft function (DGF)and slow graft function (SGF) in improving graft function and delaying chronic allograft nephropathy. The investigators hypothesize that conversion from tacrolimus to sirolimus in renal transplant recipients with DGF/SGF in early months after surgery will improve graft function and decrease the progression of graft fibrosis.
This study will examine whether measurements of connective tissue growth factor (CTGF) and other cell proteins can identify which kidney transplant recipients are likely to develop chronic allograft nephropathy (CAN), a disease of the transplanted kidney. CAN may occur months to years after the transplant. The kidney becomes progressively scarred and eventually loses all function, so that dialysis or another transplant is needed. A better understanding of how CTGF and other proteins are involved in the development of CAN may provide new targets for treating for the disease. Patients who are scheduled to receive a kidney or combined kidney-pancreas transplant or who have received a transplant recently (within 6 months) may be eligible for this study. Participants will be enrolled before the transplant, if possible, or after the transplant, and will undergo the following tests and procedures: * Physical examinations at the screening visit, at 1, 6, 12, and 24 months, and then once yearly. * Blood sample collections at the screening visit, at 1, 6, 12, 18, and 24 months and then once yearly. * Urine sample collections at the screening visit, at 1, 6, 12, 18, and 24 months and then once yearly. * Kidney biopsies at the beginning of the study, at 1, 6, 12, and 24 months, and then once a year for research purposes. Participants may refuse to have a research biopsy at any time during the study. Also, patients who are having a kidney biopsy for another reason at these time points will not have a second biopsy. The biopsy procedure takes about 15 minutes and is done in the hospital. The patient lies on his or her back and the skin over the transplanted kidney is cleaned with alcohol and iodine. The area is numbed with an injection of an anesthetic, and then a biopsy needle is placed through the kin. The biopsy may be repeated up to three times to get enough tissue to test for CAN. Patients lie flat for 4 hours after the procedure to reduce the risk of bleeding, and are observed for another 2 hours for possible complications.
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.
This double-blind, randomized, placebo-controlled, multinational, multicenter, parallel-group, Phase 3, 2-arm, study will investigate the efficacy and safety of belumosudil compared with placebo, both administered on top of azithromycin and standard-of-care regimen of immunosuppression in male or female participants at least 1 year after bilateral lung transplant, who are at least 18 years of age and who have evidence of progressive CLAD despite azithromycin therapy. Study details include: The study duration will be up to 31 weeks for participants not entering the open-label extension (OLE) period and up to 57 weeks for participants entering the OLE period but not the long-term OLE. The treatment duration will be up to 26 weeks for participants not entering the OLE period and up to 52 weeks for participants entering the OLE period but not the long-term OLE. The number of visits will be up to 10 visits for participants not entering the OLE period and up to 16 visits for participants entering the OLE period but not the long-term OLE. For participants who enter the long-term OLE, treatment and study participation will continue with visits every 12 weeks per protocol specifications.
This study will use Magnetic Resonance Imaging (MRI) to study the lungs of 90 volunteers using the inhaled contrast agent, hyperpolarized xenon-129. Once inhaled, this gas can provide information to imagers regarding lung functionality across specific regions of the lungs by assessing the replacement of air during the normal breathing cycle, how much oxygen is in the airspaces, and if the natural spongy tissue structure has been compromised by lung disease. Of the 90 subjects, 70 will be patients who received lung transplantation from the Penn/Temple Lung Transplant Teams and are receiving follow up treatment at HUP or TUH, 10 will be healthy control subjects who participated favorably in our HP 129Xe imaging protocol, and 10 will be patients who have been diagnosed with chronic obstructive pulmonary disease (COPD)-preferentially recruited from the Temple University COPDGene cohort, who have never undergone a lung transplant. 20 of the lung transplant recipient subjects will be patients who have received a recent clinical diagnosis of chronic lung allograft dysfunction (CLAD) prior to enrollment in our study, while the other 50 will have recently undergone their initial transplant surgery at the time of enrollment.
Greater than 50% of lung transplant recipients show signs of chronic lung allograft dysfunction (CLAD) by 5 years post-transplantation.Therapies to prevent or slow CLAD are lacking. Anti-fibrotic therapies may offer an avenue to prevent progression of CLAD and prolong allograft survival. This study investigates if Pirfenidone therapy will stabilize lung function decline and slow progression of Functional small airways disease (fSAD) in lung transplant recipients with CLAD.
Despite advances in lung transplantation, the median survival remains only 55% at 5 years. The main limitation to long term survival is the development of chronic lung allograft dysfunction. In approximately 30% of cases, chronic lung allograft dysfunction has a restrictive phenotype (RCLAD) characterized by fibrosis with rapid progression to respiratory failure. Approximately 60% of patients with RCLAD die within one year, as currently there are no therapies available. RCLAD, like Idiopathic Pulmonary Fibrosis (IPF), is characterized by fibroblast proliferation, extracellular matrix deposition, and architectural distortion leading to progressive lung scarring and death. Given their similarities, there is keen interest in the international transplant community to investigate whether the anti-fibrotic drug pirfenidone can slow the progression of RCLAD as it does of IPF. Pirfenidone has been proved to be safe and effective in patients with IPF, and is approved by the Food and Drug Administration. This protocol will evaluate the safety and tolerability of pirfenidone in lung transplant recipients with RCLAD. Transplant recipients take carefully adjusted immunosuppressive medications for life to prevent rejection of the allograft. Current literature suggests the dose of tacrolimus, the main anti-rejection drug, may need to be adjusted when taken in combination with pirfenidone. The investigators will assess the side effects of pirfenidone in combination with the immunosuppressive regimen and determine the magnitude of the adjustment in tacrolimus dose. The results of this pilot study will provide the foundation for a multicenter randomized control trial to evaluate the efficacy of pirfenidone in slowing the progression of RCLAD.
Potential therapy with MACITENTAN in the treatment of Chronic Lung Allograft Dysfunction (CLAD) after Lung Transplantation. Pilot Study, Double-blind, "ADD-ON Therapy" with MACITENTAN to "usual standard of care immunosuppressive therapies" after lung transplantation for established BOS Stages I or II versus a "matched control group" who receive "usual standard of care immunosuppressive therapies" alone, results in a decrease in the Primary Endpoint: "rate of decline" in "Forced Expiratory Volume-1 sec (FEV1) versus time" while Secondary Endpoints including: differences in Six minute walk distance (6MWD), BORG Score, corrected single-breath diffusing capacity (DCO corrected) at time intervals of 1, 3, 6 months on therapy. Specific biomarkers for BOS, including inflammatory chemokines, which are routinely collected in the context of post-transplant "surveillance" will be analyzed. Chemokines which our group has previously described in the pathogenesis of the continuum of "acute-to-chronic lung allograft rejection", have included both C-C (CCL2, CCL5) and CXC (CXCL9, CXCL10, CXCL11) chemokines as determined in bronchial-alveolar lavage (BAL).
A study to compare the conversion to Prograf® (tacrolimus) to the continuation of cyclosporine in patients at risk for chronic renal allograft failure
The purpose of the study is to follow participants who enrolled in the Lung Transplant Outcomes Group. Clinical data, functional assessments, and surveys will be collected to determine long term graft function and functional status of lung transplant recipients.
The purpose of the study is to continue to follow subjects who were enrolled in the CTOT-20 CLAD Phenotypes study. Subjects will provide clinical data and complete quality of life questionnaires that will be used to determine the clinical factors associated with the development of Chronic Lung Allograft Dysfunction (CLAD) after lung transplant.
The goal of this clinical trial is to learn about the safety and effectiveness of LAM-001 in patients who have developed bronchiolitis obliterans syndrome (BOS), a form of chronic rejection, after lung transplantation. The main questions it aims to answer are: * Is LAM-001 safe in these patients? * Is LAM-001 effective in slowing BOS progression? Participants will: * Be randomly assigned to inhale either LAM-001 or placebo (a look-alike substance that contains no active drug) daily for 48 weeks * Attend 10 study visits (mixture of in-person and telehealth) over the 48 week period * Undergo pulmonary function testing, bronchoscopy, lab testing, and physical examination * Submit weekly home spirometry monitoring Researchers will compare participants assigned to LAM-001 versus placebo to see if LAM-001 is safely tolerated and to assess the effectiveness of LAM-001 on slowing BOS progression.
The objective of the trial is to assess efficacy and safety of add-on aerosolized liposomal cyclosporine A (L-CsA) to Standard of Care (SoC) therapy as compared to SoC therapy alone in the treatment of Bronchiolitis obliterans syndrome (BOS) in single lung transplant recipients.
The objective of the trial is to assess efficacy and safety of add-on aerosolized liposomal cyclosporine A (L-CsA) to Standard of Care (SoC) therapy as compared to SoC therapy alone in the treatment of Bronchiolitis obliterans syndrome (BOS) in double lung transplant recipients.
The investigators will evaluate for early evidence of cardiac allograft dysfunction by cardiac MRI and single cell sequencing to determine underlying molecular and macroscopic causes.
The investigators will use cardiac MRI to measure the myocardial perfusion reserve and amount of myocardial edema and fibrosis in heart-transplant patients with nonspecific allograft dysfunction in contrast to those with normal graft function. The investigators hypothesize that patients with nonspecific allograft dysfunction will demonstrate decreased myocardial perfusion reserve, related to microvascular allograft vasculopathy, compared to those with normal graft function.
In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their transplant. This clinical trial will study this method in a greater number of people to determine if it is indeed effective and safe.
The purpose of this study is to determine if analysis of urine samples for specific markers can predict transplant rejection in people who have received kidney transplants.
The TEAMMATE Trial will enroll 210 pediatric heart transplant patients from 25 centers at 6 months post-transplant and follow each patient for 2.5 years. Half of the participants will receive everolimus and low-dose tacrolimus and the other half will receive tacrolimus and mycophenolate mofetil. The trial will determine which treatment is better at reducing the cumulative risk of coronary artery vasculopathy, chronic kidney disease and biopsy proven-acute cellular rejection without an increase in graft loss due to all causes (e.g. infection, PTLD, antibody mediated rejection).
In pediatric kidney transplant patients, rejection, medication toxicity and ischemia cause early and chronic renal allograft injury, which reduces graft lifespan and patient survival. Early detection of injury would facilitate prevention and treatment. The gold standard surveillance biopsy has limitations including delayed discovery of injury. No noninvasive test identifies graft injury before it is clinically apparent. This project's goal is to develop a novel early marker of subclinical graft injury to facilitate prompt recognition and treatment.