February 2023
In the early stages of her pediatric training, Claudia Morris, MD saw herself primarily as a clinician, with “research” being a necessary process only to sit for her pediatric emergency medicine (PEM) sub-specialty boards. However, before attending medical school she worked as a technician in a lab focused on nitric oxide biology, where she encountered many outside-the-box thinkers who unexpectedly altered her career path. In particular, Dr. Morris had a mentor in that lab who made a significant impact on her, showing her the importance of good mentorship early on, which she has since adopted in her own career. Serendipitously, she was able to apply what she learned about the arginine-nitric oxide pathway in that lab to a novel treatment in sickle cell disease (SCD) 10 years later. This shifted her career goal from being a clinician to that of a clinician-scientist. Now, Dr. Morris has been involved in clinical and translational research for over 25 years, and holds the Wilbur Fisk Glenn Jr. Distinguished Faculty Chair as Co-Director for the Emory+Children’s Center for Clinical & Translational Research.
Under the leadership of Dr. Morris, the Emory Department of Pediatrics (DOP) and its Children's PEM division joined the prestigious Pediatric Emergency Care Applied Research Network (PECARN) in 2019. PECARN performs "high-quality, multi-center research into the prevention and management of acute illnesses and injuries in children across the continuum of emergency medicine health care," and is funded by HRSA since 2001. It consists of 18 sites and 6 nodes, including the San Francisco-Oakland, Providence, Atlanta Research Collaborative (SPARC) node, which includes all three of Children's pediatric emergency department campuses in Atlanta. Dr. Morris is the site principal investigator (PI) for SPARC, with additional PECARN leadership provided by co-investigators Hal Simon, MD and Mark Griffiths, MD. PECARN forms an infrastructure for PIs to ask questions that are a priority in PEM. Once PIs have a research idea, they pitch the idea to the network, and if they get approval, they have a high success rate of securing federal funding. Being a part of PECARN has increased the academic productivity of the PEM Division. At least 18 DOP members are involved in PECARN studies or working groups that include not only PEM faculty, but also interdisciplinary champions in pediatric nephrology, critical care, asthma, trauma, and neurology.
PECARN participation has also significantly increased PEM-related NIH funding to the DOP. When Dr. Morris arrived at Emory DOP in 2012, the PEM division had just over $200,000 in research grant funding annually and one research coordinator. In 2022, PEM contributed over $2.3 million in research dollars to the DOP, with an expanding pipeline of new funding, and a PEM research team that has grown to include over 20 research coordinators, nurses/nurse practitioners, post-doctoral fellows, research managers/ directors and research interns to support the performance and dissemination of high-quality research.
As the PEM Research Director, Dr. Morris has also been successful in expanding the research platform beyond PECARN, and engaging an increasing number of PEM physicians in research pursuits and leadership. For example, PEM physicians Lauren Middlebrooks, MD and Mark Griffiths, MD were recently named recipients of the Gilead FOCUS award to develop a replicable model project at Children’s that embodies best practices in HIV screening and linkage to care in collaboration with our infectious disease partner Andres Camacho-Gonzalez, MD. This award will help the team to implement the 2007 CDC recommendations around universal HIV screening of adolescents in pediatric emergency departments. Additionally, the PEM Division has also been awarded a competitive U.S. Department of Health and Human Services grant along with six other sub-sites, to become the third Regional Pediatric Disaster Care Center of Excellence through collaboration between PEM faculty David Greenky, MD and Andi Shane, MD, Division Chief of Infectious Diseases.
Dr. Morris is a dedicated clinical trialist, best known for her research in sickle cell disease (SCD). In 1997, a decade after her work in the nitric oxide lab, she realized that the vasoconstriction causing pain in SCD could be due in-part to an arginine deficiency. Arginine is an amino acid found in a regular diet, and the body uses it to produce nitric oxide. Dr. Morris and her team conducted a proof-of-concept study to determine if patients with SCD and acute pain had low arginine levels in their blood. Funded by a small CTSA pilot grant, they found that arginine and nitric oxide levels were indeed low in SCD patients presenting with acute pain, and arginine supplementation increased nitric oxide metabolites in their blood. Dr. Morris then led a phase 2 randomized control trial of arginine supplementation in children with SCD and pain, supported by a K23 Career Development Award from the NIH. The study showed that this nutritional supplement decreased total intravenous (IV) opioid use by 55%, and significantly reduced pain scores at discharge. It also showed trends of decreased length of hospital stay. She has subsequently worked with collaborators in Nigeria, where an additional phase 2 trial show that oral arginine significantly decreased hospital stay for children with SCD and pain by nearly 48 hours, improved heart function and significantly decrease pain scores and medications used for pain, when compared to placebo. She also recently completed another phase 2 trial of IV arginine therapy at Emory & Children’s with outcomes nearly identical to her first published clinical trial. As a result of these promising studies, NIH awarded Emory an $8.7M to perform the definitive phase 3 trial entitled Sickle Cell Disease Treatment with Arginine Therapy (STArT trial), which has the potential to change management for children with SCD experiencing pain. In this study, 360 patients need to be enrolled in order to demonstrate if there is an actual decrease in time of pain requiring treatment with IV opioids. There are 10 PECARN sites for this study across the country, and 135 patients have already been enrolled within the first 18 months. Eligible patients with SCD and their parent or guardian who wish to enroll are randomly assigned to receive either arginine or a placebo, and take the study drug treatment through an IV three times a day up to 7 days of hospital stay or until they are discharged from the hospital, whichever comes first. Patient reported outcomes and research blood work is collected as part of the study, creating the largest biorepository of blood samples from children and young adults with SCD experiencing acute pain, to help answer future questions around pain mechanisms.
A secret to success in SCD studies that enroll in the emergency department is a dedicated team of research coordinators, and a strong collaboration between PEM and hematology investigators among all participating sites, including hematology co-I’s Nitya Bakshi, MD and Carlton Dampier, MD at Emory and Children’s. Acute pain in SCD is currently treated by supportive care and IV opioids, but there’s challenges with these treatments. Right now, there are no Food and Drug Administration (FDA)-approved drugs to help with acute SCD-related pain. Dr. Morris aims to develop a drug that will improve pain and be initiated in the emergency department. She is working closely with the FDA so that this therapy can be implemented nationally if the STArT trial ultimately supports the use of arginine therapy.
Arginine dysregulation continues to be a research interest for Dr. Morris. During the COVID-19 pandemic, Dr. Morris noticed there were some overlapping complications in children with COVID-19 similar to patients with SCD that included endothelial dysfunction, acute lung injury and a high frequency of blood clots (coagulation abnormalities) that could be caused in-part by arginine dysregulation. To investigate this further, Dr. Morris and PEM faculty Chris Rees, MD conducted a pilot study evaluating amino acids in adults and children sick enough to be hospitalized with COVID-19. They were the first to identify a significant arginine deficiency in these patients compared to normal controls. As a result of this work, Dr. Morris is now seeking funding for a new arginine intervention study in children hospitalized with COVID-19, furthering her focus on arginine deficiency syndromes.