Chris Larsen and Ravi Rajani Receive Synergy Awards

October 2017

Transplant surgeon-scientist Christian Larsen, MD, DPhil, and vascular surgeon-scientist Ravi Rajani, MD, were among the faculty selected to receive funding in the third cycle of Synergy Awards. The awards support collaborative projects among faculty at Emory University School of Medicine, Rollins School of Public Health, Nell Hodgson Woodruff School of Nursing, Yerkes National Primate Research Center, Winship Cancer Institute, and all other units in the WHSC, and are funded from the Office of the Executive Vice President for Health Affairs.

Proposals for Synergy Awards are required to include faculty members with primary appointments in at least two different schools/units as co-principal investigators. The awards are intended to support new, highly innovative projects that are not yet funded or published, and offer up to $100,000 in support for an award term of one year, with potential carryover to a second year under special circumstances.

Smartphone-Enabled Supervised Exercise Therapy for the Treatment of Symptomatic Peripheral Arterial Disease

Dr. Rajani will be collaborating with epidemiologist Amit J. Shah, MD, of the Rollins School of Public Health, and cardiologist Nanette K. Wenger, MD, of the Department of Medicine, on this project, which will evaluate the use of a specialized smartphone app as a home exercise initiator and tracker for patients with peripheral arterial disease (PAD), a circulatory problem in which narrowed arteries reduce blood flow to the limbs.

Supervised exercise therapy (SET) is associated with significant improvements in functional status and overall quality of life in PAD patients, though it is generally underutilized. Recent studies have shown that structured home-based exercise (SHE) could be akin to SET in positive effects, thereby offering a suitable alternative for patients whose access to a center-based program is limited by one or more factors.   

The team will use an app developed by Moving Analytics that features daily reminders to exercise; a virtual diary for patients to enter data on exercise sessions, blood pressure, weight, and medication adherence; two-way secure messaging with a designated health coach; synchronization with the health coach's online dashboard; and educational videos on heart and vascular health. The app can also integrate with other wearable devices for sharing real-time data such as Fitbit activity trackers.

The first aim of the study will be to evaluate changes in functional capacity, engagement, health behaviors, and quality of life after 12 weeks of smartphone-enabled vs standard SHE in 50 patients with symptomatic PAD at the Atlanta VA Medical Center and Grady Memorial Hospital. Dr. Rajani and his colleagues suspect that all subjects will show improvements compared to baseline, though they believe those in the smartphone-enabled arm will be more engaged and satisfied with their care, and show more improvements in walking distances, self-reported quality of life, lower smoking rates, better eating habits (more fruits and/or vegetables), and better medication adherence.

The study's second focus will be to analyze such provider differences as time spent with patients and overall satisfaction in the smartphone-enabled vs. standard SHE arms. Drs. Rajani, Shah, and Wenger propose that providers will deliver the intervention in less time and with more satisfaction when utilizing the smartphone dashboard vs standard (telephone only) program.   

Metagenomic Cartography of the Virome in Transplant Recipients

Dr. Larsen and biostatician Yi-Juan 'Yijuan' Hu, PhD, of the Rollins School of Public Health, will be co-principal investigators on this study, and their team will include additional investigators Mandy Ford, PhD, scientific director of the Emory Transplant Center, and Aneesh Mehta, MD, assistant director of transplant infectious diseases at Emory University Hospital. Using their combined experience in transplantation, immunosuppression studies and development, and bioinformatics, the team hopes to quantify and qualify the effects of belatacept vs tacrolimus immunosuppression on transplant recipients' virome, the myriad collection of viruses within human blood and tissues that can influence organ function, inflammation, and immunity to pathogens and transplanted tissues.

Belatacept, co-developed by Dr. Larsen and used by the Emory Transplant Center (ETC) as its primary immunosuppressant for kidney transplant recipients since the FDA's approval of the drug in 2011, is a costimulation blocker that interferes with T cell function and halts immune rejection of a transplanted organ. Belatacept avoids the damage to the kidney and cardiovascular system observed with the cornerstone transplant drugs known as calcineurin inhibitors (CNI), such as tacrolimus. The immune system exerts selection pressure on both pathogenic and symbiotic microbes that colonize organisms, a process which the team hypothesizes could be modified by the costimulatory signals blocked by belatacept. Therefore, they plan on observing and exploring any changes in the composition of patients' viromes after the inception of immunosuppression with either belatacept or tacrolimus.

Using such methods as high throughput sequencing technologies, which arrange, analyze, and compare large numbers of genomes (an organism's complete set of DNA); bioinformatic and biostatistical assessment strategies; and other high-powered approaches to surveying genetic material; Dr. Larsen and his colleagues will document the activities of the virome over time in ETC kidney transplant patients who are receiving either tacrolimus or belatacept-based immunosuppression. Samples obtained from ten recipients per treatment group will be examined prior to transplant, and at the first, third, sixth, ninth, and 12th months post-transplant.

Normally, this type of comparative pilot study could not have been conducted at Emory due to the ETC's use of belatacept-based immunosuppression for the majority of its kidney transplant recipients. However, belatacept production capacity issues in 2017 made it necessary for the ETC to use tacrolimus instead, and as samples from this patient group were tissue-banked, the opportunity for doing this study arose. Belatacept production is expected to resume in January 2018, at which point the ETC will resume its belatacept-based regimen and begin acquiring samples for the belatacept cohort of the study.

In addition to leveraging the study's results to apply for NIH funding to examine the impact of viral dynamics on transplant outcomes across multiple centers, Dr. Larsen and his collaborators believe the study's preliminary data will begin to identify how specific changes in the human virome may be associated with incidence of infection, rejection, and other disease metrics in transplant recipients.

These findings could be used to bolster future proposals for projects to further refine the immunosuppression process, and could establish new, collaborative lines of academic inquiry and eventually lead to improved outcomes for transplant patients.

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