Research Overview: Transplantation

Micromed (320x240)
credit: Courtesy Texas Heart InstituteMicromed VAD

Researchers in the Division of Cardiothoracic Transplantation and Circulatory Support work in concert with the Texas Heart Institute, one of the highest volume and most prestigious mechanical circulatory support programs in the world. The expertise of visionary surgeons O. H. Frazier, M.D., professor of surgery, and George P. Noon, M.D., professor of surgery, led to the development of continuous flow left ventricular assist devices (LVADs), the most common in worldwide clinical use today.

Dr. Frazier is credited with developing the first FDA-approved implantable LVAD, the HeartMate, and the first FDA-approved continuous flow pump, the HeartMate II, and many other groundbreaking lifesaving devices. Currently, Dr. Frazier and William E. Cohn, M.D, professor of surgery at Baylor and director of the Center for Device Innovation @ TMC, are working on developing a total artificial heart that will deliver blood by means of continuous flow rather than pulsation, a project supported by NIH grants and generous benefactors.

Our liver transplant program, directed by John A. Goss, M.D., professor and chief of the Division of Abdominal Transplantation, is the largest in Houston’s Texas Medical Center and one of the busiest in the nation. Faculty in the Division of Abdominal Transplantation are committed to research in areas such as adult and pediatric solid organ transplantation, liver disease, kidney disease, immunogenetics, bone marrow transplant outcomes, and chronic hepatitis C virus.

In part funded by NIH grants, the Advanced Liver Therapies at Baylor St. Luke’s Medical Center, directed by John M. Vierling, M.D., professor of medicine and surgery, offers patients access to the latest clinical trials, including those testing therapies for chronic viral hepatitis B and C infections and treatments for thrombocytopenia in liver disease. Faculty associated with the Immune Evaluation Laboratory at Baylor conduct studies on cellular and antibody immune responsiveness in relation to graft rejection, and immune response to allogenic stem cell infusions for heart failure patients.

Research by Division

Cardiothoracic Transplantation and Circulatory Support

TransMedics Organ Care System (320x240)
credit: Scott HolmesTransMedics Organ Care System

Improved Donor Lung Preservation and Quality Using Ex Vivo Lung Perfusion Platforms

Gabriel Loor, M.D., surgical director of the Lung Transplant Program at Baylor St. Luke’s Medical Center, is the principal investigator of several international trials using ex vivo lung perfusion platforms to increase donor yield and quality, and maximize recipient outcomes. Dr. Loor is national PI for the multicenter International EXPAND Lung Pivotal Trial (EXPANDLung) (NCT01963780), sponsored by TransMedics, Inc. The EXPAND trial will evaluate if the TransMedics Organ Care System (OCS) system—a portable device developed to overcome the limitations of cold storage—could recruit, preserve and assess donor lungs that do not meet current acceptance criteria for transplantation. This research builds upon the encouraging findings of the INSPIRE International Lung Trial with TransMedics OCS Technology (NCT01630434), also led by Dr. Loor (national PI), revealing that donor lungs preserved using the OCS system significantly reduced incidents of primary graft dysfunction grade 3 (PGD3) after transplant as compared to lungs preserved using cold storage.

A New Pulseless Artificial Heart on the Horizon

Researchers working under the leadership of O. H. Frazier, M.D., professor of surgery at Baylor and chief of cardiopulmonary transplantation at Texas Heart Institute, and William E. Cohn, M.D, professor of surgery and director of the Center for Device Innovation at TMC/Johnson & Johnson Innovations, are developing a total artificial heart that will deliver blood by means of continuous flow rather than pulsation. Dr. Frazier and Dr. Cohn’s research team has received grants from the NIH-NHLBI and private donors to further this research. This new artificial heart uses rapidly spinning rotors like those found in some types of ventricular assist devices (VADs), to produce continuous flow. Laboratory studies supported by foundation grants have confirmed the feasibility of this new continuous flow artificial heart.

The team began working with Dr. Daniel Timms, a biomedical engineer from Australia, who has designed a device called the BiVACOR to support or totally replace the heart. The BiVACOR is a small, lightweight and deceptively simple machine. It uses a magnetic field, a spinning disc and centrifugal force to pump blood. Because there is only a single moving part and no friction, it is expected to be durable.

Abdominal Transplantation

DHNB Structure (320x240)
credit: Scott HolmesDHNB Structure

Dr. Vierling Co-Authors NEJM Article on HCV Treatment

John M. Vierling, M.D., professor of Surgery and Medicine in the Division of Abdominal Transplantation at Baylor College of Medicine, co-authored an article in the June, 2017 issue of the New England Journal of Medicine. It is the first publication on the safety and efficacy of a new triple drug regimen (formulated into a single pill taken once daily) for the treatment of patients who previously failed to achieve a sustained virologic response (SVR, which represents a cure of the HCV infection) after prior treatment with direct-acting antiviral (DAA) agents.  Patients who relapse after DAA therapy typically have resistance-associated substitutions (RASs) that confer resistance and defeat attempts to retreat patients successfully. The sponsor is Gilead Sciences, and the three drugs are sofosbuvir (NS5B nucleotide inhibitor), velpatasvir (NS4A replication complex inhibitor) and voxilaprevir (NS3/4A protease inhibitor).  The combination is effective against all 6 genotypes of HCV.

Dr. Vierling directs Advanced Liver Therapies at Baylor St. Luke’s Medical Center, a clinical research unit devoted to clinical trials of new diagnostics and therapeutics in adult hepatobiliary diseases. His primary research interests are the immunopathogenic mechanisms involved in hepatobiliary injury caused by viral hepatitis, autoimmunity, alloimmunity, and non-alcoholic fatty liver disease.

Metabolomic Signature of Altered Hemodynamics in Subjects with Cirrhosis

Ayse L. Mindikoglu, M.D., M.P.H., associate professor in the Division of Abdominal Transplantation, was awarded a grant from the MacDonald Fund at Baylor St. Luke’s Medical Center for her proposal, “Metabolomic Signature of Altered Hemodynamics in Subjects with Cirrhosis.” This metabolomics signature may prove valuable for patients with cirrhosis as a predictor of outcomes after successful therapy of hepatorenal syndrome.

Advanced Liver Therapies Research at Baylor St. Luke’s Medical Center

Directed by NIH-funded investigator, John Vierling, M.D., professor of surgery and medicine, Advanced Liver Therapies at Baylor St. Luke’s Medical Center is a clinical research center for liver diseases affiliated with the Baylor College of Medicine. The mission is to conduct Food & Drug Administration (FDA) approved clinical studies designed to advance the science and practice of hepatology and liver transplantation. With over 75 years of combined research experience, ALT staff endorses and practices the highest standards of ethical research, while providing opportunities for all patients to participate in clinical trials.       

Emphasizing a “laboratory bench to bedside” philosophy, Dr. Vierling has also been active in the design and execution of clinical therapeutic trials of antiviral agents for treatment of hepatitis B and C infections in patients before and after liver transplantation, and trials of immunosuppressive drugs in liver transplantation and autoimmune liver diseases.       

ALT is currently conducting clinical research in the following areas: Hepatitis C, Hepatitis B, Fatty Liver Disease, Hepatic Encephalopathy, Primary Biliary Cirrhosis, Hepatorenal Syndrome, and Anti-Fibrosis. Studies include:

Volixibat (SHP626) in the Treatment of Adults with Nonalcoholic Steatohepatitis (NASH)

Dr. Vierling is the principal investigator of a Phase 2 double-blind, randomized, placebo-controlled dose-finding study (NCT02787304), sponsored by Shire, to evaluate the safety tolerability and efficacy of Volixibat Potassium, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi) in adults with nonalcoholic steatohepatitis (NASH).

Emricasan, an Oral Caspase Inhibitor, in Subjects with Non-Alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension (ENCORE-PH)

This is a multicenter, randomized, double-blind, placebo-controlled trial (NCT02960204), sponsored by Conatus Pharmaceuticals Inc., involving subjects with NASH cirrhosis and severe portal hypertension. Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID, 25 mg BID, or 5 mg BID or matching placebo BID. Dr. Vierling is the principal investigator of the Advanced Liver Therapies Site at Baylor St. Luke’s Medical Center site.

Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients with Primary Biliary Cholangitis (COBALT)

Sponsored by Intercept Pharmaceuticals, this study (NCT0230811) will assess the effect of OCA compared to placebo, combined with stable standard care on clinical outcomes in patients with primary biliary cholangitis (PBC). If approved, it would be the first new therapy for the disease in nearly 30 years. PBC is a serious, life-threatening, blue acid related liver disease of unknown cause. Without treatment, it frequently progresses to liver fibrosis and eventual cirrhosis requiring liver transplantation or resulting in death. This investigational drug, Obeticholic Acid (OCA) is a modified bile acid and FXR agonist that is derived from the primary human bile acid chenodeoxycholic acid. Dr. Vierling is principal investigator.

Using Telemedicine Technology to Improve Quality and Delivery of Community Health Services

In 2014, Baylor St. Luke’s Medical Center launched the telehealth program, Project ECHO (Extension for Community Healthcare Outcomes), with a team of health professionals and partnering primary care providers throughout Texas. Project ECHO, led by Norman L. Sussman, M.D., associate professor in the Division of Abdominal Transplantation and medical director of Project ECHO, aims to enhance medical resources in communities in Texas that currently lack specialized care for patients suffering from illnesses, like hepatitis C or cirrhosis. The project’s videoconference outreach model uses multipoint teleconferencing to enable specialists like Dr. Sussman from university medical centers to connect with community providers in a peer-to-peer format, and uses case-based learning to teach providers to deliver state-of-the-art medical care. Currently, Project ECHO offers telementoring clinics in hepatitis C, hepatitis B, advanced liver disease, infectious disease and cardiology, with plans to expand.

Congenital Heart Surgery

Berlin Heart (320x240)
credit: Scott Holmes3D model of the Berlin Heart

Dr. Iki Adachi Leads NIH NHLBI-Supported PumpKIN Trial at Texas Children’s Hospital

Iki Adachi, M.D., assistant professor in the Division of Congenital Heart Surgery and co-director of Mechanical Circulatory Support at Texas Children’s Hospital, is the lead investigator of the funded by the National Heart, Lung, and Blood Institute-funded Pump for Kids, Infants, and Neonates (PumpKIN) study (NCT02954497), managed by the New England Research Institutes, Inc.. Dr. Adachi was part of the team that developed the Jarvik Infant 2015 (Jarvick Heart, Inc.), an implantable continuous-flow VAD (the size of an AA battery) for small children which underwent significant modifications to meet the target hemolysis levels. The team created a control system allowing speed of blood flow to be adjusted as the child grows. In December 2016, the FDA greenlighted the PumpKIN trial, a prospective, randomized two-arm multicenter international trial comparing the Jarvik 2015 VAD and the Berlin Heart EXCOR® Pediatric VAD to determine each device’s ability to provide circulatory support for children with heart failure.

Clinical Trials

Tandemheart® Experiences and Methods Theme Registry™

This study is intended to be a multicenter, prospective observation registry. By collecting prospective descriptive data, provide insight into disease defining characteristics resulting in the clinical decision to use the TandemHeart for mechanical support and enhance knowledge of best practice regarding clinical management, weaning and removal/exit strategies.

Sponsor: Cardiac Assist                                                         

Principal Investigator: Dr. Gabriel Loor

Pumps for Kids, Infants, and Neonates (PumpKIN)

This is a randomized, multicenter, two-arm trial evaluating the investigational Jarvik 2015 VAD versus the EXCOR Pediatric VAD in pediatric patients with heart failure.

Sponsor: NIH NHLBI, New English Research Institutes, Inc.

Principal Investigator: Dr. Iki Adachi

Volixibat (SHP626) in the Treatment of Adults with Nonalcoholic Steatohepatitis (NASH)

This is a Phase 2 double-blind, randomized, placebo-controlled dose-finding study (NCT02787304), sponsored by Shire, to evaluate the safety tolerability and efficacy of Volixibat Potassium, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi) in adults with nonalcoholic steatohepatitis (NASH).

Sponsor: Shire

Principal Investigator: Dr. John M. Vierling

Emricasan, an Oral Caspase Inhibitor, in Subjects with Non-Alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension (ENCORE-PH)

This is a multicenter, randomized, double-blind, placebo-controlled trial (NCT02960204) involving subjects with NASH cirrhosis and severe portal hypertension. Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID, 25 mg BID, or 5 mg BID or matching placebo BID. Sponsor: Conatus Pharmaceuticals Inc.

Principal Investigator: Dr. John M. Vierling

Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients with Primary Biliary Cholangitis (COBALT)

This study (NCT0230811) will assess the effect of Obeticholic Acid (OCA) compared to placebo, combined with stable standard care on clinical outcomes in patients with primary biliary cholangitis (PBC). If approved, it would be the first new therapy for the disease in nearly 30 years. PBC is a serious, life-threatening, blue acid related liver disease of unknown cause. Without treatment, it frequently progresses to liver fibrosis and eventual cirrhosis requiring liver transplantation or resulting in death. This investigational drug OCA is a modified bile acid and FXR agonist that is derived from the primary human bile acid chenodeoxycholic acid.

Sponsor: Intercept Pharmaceuticals

Principal investigator: Dr. John M. Vierling