Duke University among top 10 in nation for federal medical research funding

February 19, 2019 – The university ranked 9th in the United States among similar institutions.

Duke University received $384.6 million last year from the National Institutes of Health to advance medical research, ranking 9th in the country among universities, research institutions and teaching hospitals that are awarded the taxpayer-based research dollars.

Duke was the largest recipient of NIH grant funding in North Carolina for fiscal-year 2018, according to the Blue Ridge Institute for Medical Research, which publishes an annual analysis of NIH funding.

Eight clinical departments in the Duke University School of Medicine ranked among the top 10 for NIH research dollars:

  • Surgery: 1st, receiving $30.2 million in grant awards
  • Pediatrics: 2nd, receiving $39.5 million
  • Neurosurgery: 4th, receiving $8.1 million
  • Medicine: 5th, receiving $133.9 million
  • Psychiatry: 5th, receiving $39.6 million
  • Orthopedics: 6th, receiving $5.2 million
  • Anesthesia: 7th, receiving $5.8 million
  • Ophthalmology: 8th, receiving $9 million

Additionally, three basic science disciplines were also included among the top 10 for funding, including biostatistics at No. 2, with $18.3 million in grant funding; genetics at No. 9 with $19.8 million; and pharmacology at No. 6 with $15.7 million.

“Our faculty, staff and students work incredibly hard and have been very successful in bringing in research funding that allows them to search for answers to important questions about biological processes and health,” said Mary E. Klotman, MD, dean of Duke University School of Medicine. “At Duke, we are proud of our contributions in biomedical research and ultimately how those discoveries advance care for all patients.”

The NIH is the largest public funder of biomedical research in the world, investing more than $32 billion a year to advance research aimed at improving health.

Patient-generated data come with opportunities, challenges

February 12, 2019 – The DCRI’s Satasuk Joy Bhosai, MD, MPH, recently discussed the future of data-driven care.

With new wearable devices and apps entering the market every day, many clinicians have seen a proliferation of patient-generated data. In her role as chief of digital health and strategy at the DCRI, Satasuk Joy Bhosai, MD, MPH, spends her time thinking through the opportunities and challenges this data brings to clinical research. Bhosai recently shared her insights at a Duke Mobile App Gateway event.

On one hand, Bhosai said, the new age of connected health presents a way for clinicians to observe and communicate with their patients in ways they never have before. This can be beneficial because it allows clinicians to get a sense of how patients experience their condition outside of a clinical setting.

Conversely, the flood of new information means clinicians will have to sift through vast datasets to find the specific data points that are both relevant and actionable. They will also have to account for differences in individual patients when assessing the data’s clinical relevance.

Still, Bhosai said, she is confident that researchers will be able to think through these challenges and that patient-generated data will lead to new discoveries and the advancement of clinical research.

Gene therapy trial for Pompe disease begins

February 5, 2019 – Researchers, including the DCRI’s Priya Kishnani, MD, hope the study will provide more treatment options for patients with the disease.

Actus Therapeutics, a privately held portfolio company of Asklepios BioPharmaceutical, Inc. (AskBio), recently announced the dosing of the first patient in a phase I/II clinical study of ACTUS-101 in patients with Pompe disease. Pompe disease is a serious disease associated with high morbidity and often leads to premature death. There are variable rates of disease progression and different ages of onset characterized as infantile-onset and late-onset disease.

The initial clinical trial (ACT-CS101) is a study designed to assess the safety, bioactivity, and immune responses following treatment with a single infusion of ACTUS-101.

ACTUS-101 is delivered via intravenous injection and transduces the liver, leading to the continuous production of acid α-glucosidase (GAA). All study participants in this open label evaluation will receive ACTUS-101 while maintaining their current enzyme replacement therapy (ERT) with alglucosidase alfa. As the trial progresses, subjects who meet prespecified criteria for safety, transgene expression, and motor function will be eligible to suspend treatment with ERT.

The research team includes Dwight Koeberl, MD, PhD, professor of pediatrics at Duke, and Priya Kishnani, MD, Chen Family Professor of Pediatrics and member of the DCRI, who have played an integral role in the development of gene therapies that may directly address the underlying cause of Pompe disease. Koeberl has been working toward the initiation of this clinical trial for the past decade and Kishnani has been treating Pompe patients for over 20 years, including playing an instrumental role in Duke’s ERT trials in 1999 that led to FDA approval of IV alglucodidase alfa in 2006.

According to Kishnani, “If we are successful with ACTUS-101, this carefully planned therapeutic approach will bring a renewed sense of hope to the Pompe Disease community.”

Kishnani added, “This has the potential to not only be life-changing for our patients with Pompe disease but also could impact how we approach other inherited metabolic disorders. It is an exciting time in the field, with gene therapy treatment as a potential therapeutic approach for many conditions for which there is no treatment or as a way to enhance treatment outcomes.”

Blood test for specific metabolites could reveal blocked arteries

February 1, 2019 – Researchers hope to develop a test that could detect early changes in blood flow to the heart.

A pilot project by Duke and DCRI researchers suggests that in the near future, a blood test could show whether arteries carrying blood to the heart are narrow or blocked, a risk factor for heart disease.

According to the 40-person study published in the journal PLOS ONE, emergency patients who underwent a treadmill stress test and showed signs of decreased blood flow to the heart also had changes in five metabolites in their blood within two hours.

A control group of patients with normal stress tests did not show the same metabolite changes.

All study subjects had gone to the emergency department with symptoms of coronary disease, such as chest, jaw and shoulder pain.

blood sampleThe researchers hope a larger study could confirm that acute changes in these fatty acid and amino acid metabolites, which are energy sources for cells, could be an early biological indicator of restricted blood flow that could complement or even replace current tests.

“Cardiologists do a stress test to determine who’s at risk for having heart disease,” said lead author Alexander T. Limkakeng Jr., MD, lead author of the study and an associate professor of emergency medicine at Duke. “It guides them on whether they need a more invasive study like a catheterization. Augmenting the imaging of a stress test with metabolite biomarkers could make that process more accurate or more efficient.”

Previous research has suggested that metabolites could indicate heart disease, but scientists have yet to uncover the specific metabolomic signature to look for. For the Duke study, scientists evaluated the presence of more than 60 chemicals or compounds in the blood to identify the five specific metabolites that appeared to change in patients with abnormal cardiac stress tests.

The researchers hope to begin a larger study to further test this approach to detecting coronary artery disease, they said.

In addition to Limkakeng, study authors include Ricardo Henao, Deepak Voora, Thomas O’Connell, Michelle Griffin, Ephraim L. Tsalik, Svati Shah, Chris Woods and Geoffrey Ginsburg.

The research was supported by a grant from the ENhanced Academics in a Basic Laboratory Environment (ENABLE) program of the Duke Private Diagnostic Clinics and Duke University. Full disclosures and potential conflicts of interest are disclosed in the manuscript.

Interhospital transfer linked to treatment delays, worse outcomes in stroke patients

January 31, 2019 – Patients who were moved between hospitals before receiving endovascular therapy were more likely to experience adverse clinical outcomes.

Endovascular therapy (EVT) presents a good chance of saving stroke patients’ lives, but because the treatment is not available at every hospital, many patients must transfer hospitals before they can receive this chance. New research published today in Circulation indicates that stroke patients who undergo interhospital transfer experience longer delays before receiving endovascular therapy and have worse outcomes.

Shreyansh ShahThe article, authored by the DCRI’s Shreyansh Shah, MD, (pictured) and Ying Xian, MD, PhD, examined data from the American Heart Association’s Get With the Guidelines-Stroke registry, which includes ischemic stroke patients from more than 2,000 hospitals across the U.S.

The team found that between 2012 and 2017, almost 43 percent of the 37,620 patients who received EVT received the treatment after transferring hospitals. Because EVT, also known as mechanical thrombectomy, requires a trained person to administer the treatment as well as special equipment, not every hospital has the capacity to offer the treatment. However, referral rates for EVT continued to rise throughout the study period, which Xian said is because strong evidence supporting the efficacy of EVT was published in 2015.

The team found that while EVT can be effective, interhospital transfers can have consequences. Patients who transferred hospitals were more likely to develop symptomatic intracranial hemorrhage (7.0 percent versus 5.7 percent). They were also less likely to be able walk independently at discharge (33.1 percent versus 37.1 percent) or to be discharged to home (24.3 percent versus 29.1 percent).

These differences in outcomes could be at least partially attributed to longer wait times that transfer-in patients experience, said Shah, who recently received a “Stroke Care in Emergency Medicine” award from the American Heart Association and the American Stroke Association. The study examined the time from last known well to EVT initiation and found that transfer patients had a significantly longer wait time (median 289 minutes) than patients who arrived at a hospital that offers EVT (median 213 minutes). However, the transfer-in patients were more likely to have a door to EVT initiation time of less than 90 minutes upon arriving at the EVT-offering hospital (65.6 percent versus 23.6 percent).

“Patients who must transfer hospitals experience a longer wait time before receiving treatment,” Shah said. “In stroke patients, time is critical because as time progresses, the brain deteriorates and there is less we can do to salvage the brain and help the patient.”

Shah said the team’s findings will be of assistance as hospitals collaborate to create stroke systems of care.

“The reason this collaboration is needed is because everyone is starting to realize that stroke patients need treatment as soon as possible,” he said. “The only way we can deliver treatment urgently is if we join hands together across institutions.”

To avoid interhospital transfers and combat the risk of worsened outcomes, the authors of the manuscript have several recommendations. Firstly, EMS professionals need to receive more education and training so that they can accurately determine when a patient is having a stroke potentially caused by a large vessel occlusion, meaning that EVT could be beneficial. Regulatory changes would also help because they would allow EMS professionals to take these patients to the nearest hospital that offers EVT rather than requiring patients to be transported to the nearest hospital.

Another potential solution is to increase the number of hospitals that can provide EVT by creating mobile teams of specialists that are not based in a specific location. For example, Shah said, Duke has a team that moves between Duke University Hospital in Durham and Duke Raleigh Hospital, which enables Wake County stroke patients to receive treatment at their local hospital rather than be transferred to Durham.

In addition to policy and organizational changes, Xian said, it is important to continue to educate the public about symptoms of a stroke so patients will know to seek help before they miss the window for treatment. The American Stroke Association uses the acronym FAST—Face (changes in expression), Arm (difficulty moving or grasping), Speech (slurring of words), and Time (Call 911 as soon as possible).

PRECISE begins enrollment, looks to improve CT intervention

January 29, 2019 – The trial will build off findings from PROMISE and PLATFORM, which looked at similar patient populations and involved many of the same investigators and operational staff.

A DCRI team has begun enrollment for a clinical trial investigating the optimal evaluation strategies for people with symptoms of coronary artery disease.

PRECISE, or Prospective Randomized Trial of the Optimal Evaluation of Cardiac Symptoms and Revascularization, will enroll 2,100 patients across 100 sites in the U.S, Canada, and Europe. The trial is led by the DCRI’s Pamela Douglas, MD.

Participants in PRECISE will be randomized to receive either usual care, meaning a stress test or a cardiac catheterization, or a novel, risk-based evaluation intervention. Those in the intervention group will be evaluated for their risk of having obstructive coronary artery disease and cardiac events using the minimal risk score developed using the PROMISE trial cohort, which was also led by Douglas. That trial showed that coronary CT angiography is a viable alternative to stress testing among low- to intermediate-risk patients presenting with chest pain.

In PRECISE’s intervention arm, patients’ risk will determine the type of evaluation and treatment they will receive. The 20 percent at lowest risk will be treated medically — which includes optimally controlling risk factors, lowering blood pressure and cholesterol, and prescribing antianginal medication for chest pain. However, they will not immediately receive a diagnostic test. The other 80 percent of participants will receive a CT scan followed by fractional flow reserve (FFRct) analysis of the CT images if intermediate stenosis lesions are found.

“We wanted to have the ability to prospectively examine, in a randomized trial, whether we can safely and efficiently provide less care to very low-risk patients,” Douglas said. “Testing is expensive, so can we safely and effectively just treat the risk factors and symptoms that we’re going to need to treat anyway? We don’t do that often in medicine — it’s an unusual thing. We’re always adding a new medicine or a new treatment, so we don’t usually evaluate less (testing), with the same rigor of a randomized trial.”

The reason the team chose a graded intervention based on risk, Douglas said, is because of the very low event rates seen during the 10,000-participant trial PROMISE, in which only 1 to 1.5 percent of participants per year experienced heart attack or death. Douglas hypothesized that the team will see virtually no events in the lowest risk 20 percent population in PRECISE.

Results from PROMISE suggested that testing often occurred when it was not necessary. Of those who had CT angiograms in PROMISE, almost 90 percent did not have obstructive coronary disease, and only 4 to 8 percent ended up receiving an angioplasty or bypass surgery.

To identify the lowest risk patients, the team studied those PROMISE patients with no plaque in their coronary arteries and no events (about a quarter of the trial) and built a model to predict those patients using typical data available to a physician in the office on initial evaluation, including age, gender, and risk factors.

Once the risk score was developed, it was confirmed in a similar population in a Scottish trial called SCOT-HEART.

“Because the risk score was confirmed in a completely different population, this gives us reason to believe it is a very robust assessment,” Douglas said.

The team behind PRECISE hopes to improve the CT intervention used in PROMISE by adding FFRct, a relatively new technology. FFRct was previously studied by DCRI researchers in the PLATFORM trial.

“PLATFORM showed that when FFRct analysis was conducted on patients headed to the catheterization lab, 60 percent of the catheterizations were canceled because the CT information showed that they didn’t need to do an invasive and expensive test,” Douglas said, adding that this amounted to about a $3,000 savings per patient.

Douglas said that using both the PROMISE minimal risk score and CTA with FFRct analysis in the PRECISE population could help doctors develop a better chest pain evaluation strategy than conventional testing, which will prevent unnecessary catheterizations and reduce costs.

Douglas said she is fortunate to have the majority of the team — both faculty and operational staff — who worked on PROMISE and PLATFORM also working on PRECISE. She said the trial will benefit from the team members’ past experiences. One of those team members is project leader Beth Martinez. When PRECISE began enrollment, the team had the advantage of knowing which sites had enrolled well for PROMISE, Martinez said. Douglas reached out to the top enrolling sites personally to invite them to participate.

“There is a high volume of patients coming in with undiagnosed chest pain, so enrollment should go pretty smoothly,” Martinez said. “We have been pleased to see robust enrollment in the first few weeks.”

Another crucial part of the trial operations is the outcomes group, which consists of the outcomes call center and the economics team. The call center, led by Tina Harding and Khaula Baloch, will contact patients starting at 45 days after enrollment to assess patient-reported outcomes such as medications being taken, hospitalizations, and quality of life. Relying on the outcomes call center to gather trial data can relieve burden on sites and reduce trial costs, Martinez said. In addition, the outcomes economic Team will request hospital bills for all U.S. subjects as part of the secondary aims to compare medical costs between the groups.

Other DCRI faculty working on the project include Daniel Mark, MD; Hussein Al-Khalidi, PhD; Manesh Patel,MD, and DCRI Fellow Michael Nanna, MD. Melissa Daubert, MD, serves as the Duke site principal investigator.

PRECISE is funded by HeartFlow, the company that develops the FFRct software.

American Heart Association, Duke Margolis Center issue call to action on cardiovascular disease prevention and treatment

January 24, 2019 – A new collaboration between the two institutions aims to address continued challenges in access and affordability of cardiovascular care.

A special report published this week in the journal Circulation calls for urgent action to counter the toll from heart disease, currently the leading cause of death in the United States and worldwide. The “Presidential Advisory,” which introduces a joint initiative on value in cardiovascular care between the American Heart Association (AHA) and the Duke Margolis Center for Health Policy, includes former FDA Commissioners Robert M. Califf, MD (DCRI founder and director of Duke Forge) and Mark McClellan, MD, PhD (director, Duke Margolis Center) as co-authors.

The advisory summarizes recent data showing that long-standing trends toward progress in the treatment and prevention of heart disease have stagnated and in some cases even reversed. The article’s authors, who also include AHA Past President John Warren, MD (University of Texas -Southwestern Medical Center) and AHA CEO Nancy Brown, note that these challenges are occurring as the pipeline of therapeutic innovation is slowing, costs of cardiovascular care are rising, and patients are increasingly concerned about the value of the care they receive relative to its expense.

In addition, long-standing disparities in risk factors and access to care according to race, ethnicity, and gender have remained stubbornly persistent. The authors also note multiple missed opportunities for preventing cardiovascular disease through early diagnosis, administering effective treatments, working to modify risk factors, and communicating directly about patients’ health goals and needs.

Against this background, the authors propose creating a series of collaborative learning teams, pilot studies, and patient surveys designed to improve understanding of pathways for effectively treating and preventing cardiovascular disease, and articulate possible solutions that take the perspectives of all stakeholders into account. These efforts will ultimately inform the creation of detailed “roadmaps” for providing greater value in cardiovascular care and ensuring a robust pipeline of therapeutic development and innovation.

Scholarship to honor Kevin Thomas’ advocacy for underrepresented populations

January 23, 2019 – The Kevin L. Thomas, MD Scholarship will be awarded to high school students interested in medical careers.

The DCRI’s Kevin Thomas, MD, has devoted his career to eliminating disparities for patients with cardiovascular disease and helping junior faculty from underrepresented populations advance their medical careers. Thomas’ efforts will now extend to high school students thanks to a new scholarship that has been established in his name.

The Kevin L. Thomas, MD Scholarship will benefit participants in the Health Professions Recruitment and Exposure Program (H-PREP). H-PREP, which has programs at medical schools nationwide, introduces high school students from underrepresented populations to careers in the health sciences. The scholarship will allow H-PREP administrators at Duke to increase the amount of money provided to each participant.

Thomas, who serves as assistant dean for underrepresented faculty development at the School of Medicine and director of faculty diversity and health disparities research at the DCRI, said that at each step in his own career — from medical school to residency to a fellowship to becoming a faculty member — he has identified mentors and been supported by a network of peers.

“As I have advanced through my career, it’s always been important to give back and serve in that capacity for others,” Thomas said. “I find enjoyment in my own success, but maybe even more enjoyment in the success of others’ whose lives I can touch, whether it’s through mentorship, sponsorship, or giving general advice about career paths and development.”

In 2017, Thomas launched a yearlong program to provide professional development for historically underrepresented groups. The first cohort in the program, called Academic Development, Advocacy, Networking, Coaching, and Education for Underrepresented Populations (ADVANCE-UP), was composed of 13 faculty from eight different departments. Most of the participants were Hispanic, Latino, or African-American, and 11 of them were women, which Thomas said fostered important discussions about the intersection between race, ethnicity, and gender.

At the December closing banquet for the program, the cohort had a surprise for Thomas — they had all contributed to establish a scholarship in his name. ADVANCE-UP participants contributed $1,500 to the scholarship, and Duke School of Medicine Dean Mary Klotman matched the funds for a total of $3,000.

“The creation of this scholarship is such an affirmation of Kevin’s impact,” Klotman said. “It allows us to honor him for his incredible work as a leader and mentor, and it provides funding to help introduce research and medicine as a career to high school students from underrepresented populations. Increasing the pipeline of talented, passionate and diverse health professions students is critically important to the future of health care.”

Thomas said he was surprised by the announcement. “It’s one of the most special things I’ve ever been awarded,” he said. “I feel incredibly honored that they thought enough of me to create something like that.”

Gianna Hammer, PhD, an immunologist who has worked at Duke for five years, was a participant in the ADVANCE-UP program. She said the cohort wanted to think of a meaningful way to honor Thomas and all that he has worked for.

“The ADVANCE-UP program was a transformative experience,” she said. “Not only did it provide us with a sense of community, but it empowered and encouraged us. We wanted to also empower and encourage others, and to show Kevin that the program he created resonated. That is why we created this scholarship.”

Jennifer Dominguez, MD, another ADVANCE-UP participant and an obstetric anesthesiologist who has been at Duke for six years, said the group chose H-PREP because the program furthers Thomas’ mission.

“We felt that H-PREP was an appropriate cause to raise money for because the program enables more individuals from underrepresented populations to have access to the health sciences, and the experience may inspire them to pursue a career in medicine,” Dominguez said. “Our hope is that future cohorts of ADVANCE-UP faculty will continue contributing to this scholarship to make a sustainable impact.”

The first year of the scholarship funding will be distributed among the top three H-PREP students, who were evaluated on their performance after a series of interviews and a presentation.

Rita Kibicho, a current high school senior who wants to go to UNC-Chapel Hill, Duke, or Brown, set aside the money she received in her bank account, where she looks forward to using it on books for her first semester.

“I’d like to thank Dr. Thomas and everyone involved in H-PREP for recognizing the lack of support for younger people interested in medicine and trying to give us the exposure that will help them make tough decisions once they get to college,” she said.

Gianni Lacey-Howard, another scholarship recipient, will attend Duke on a full ride from another scholarship, but she said the Kevin Thomas, MD Scholarship will help her with miscellaneous costs associated with college.

Lacey-Howard intends to pursue a career in emergency medical services, a decision she made thanks to her experiences in H-PREP. “I know that medicine is the place I want to go because I enjoy helping people, and EMS is the best fit for me because I enjoy fast-paced thinking,” she said.

Thomas said recruitment for the second cohort of ADVANCE-UP is currently underway. Meanwhile, he is continuing his research at the DCRI on health disparities.

“We all work hard to contribute and make a difference and an impact,” Thomas said. “For me, this was validation of the hard work I’ve been able to do here at Duke thanks to the support I’ve had from many individuals across both the university and the medical system.”

The DCRI welcomes new faculty member

January 22, 2019 – Jessilyn Dunn, PhD, is a faculty member in Duke’s Departments of Biomedical Engineering; Biostatistics and Bioinformatics.

Jessilyn Dunn, PhD, joined the DCRI on January 1 as an assistant professor in Duke’s Department of Biomedical Engineering (BME) and the Department of Biostatistics and Bioinformatics. She was most recently a visiting assistant professor in the Duke Department of BME; prior to that she was a postdoctoral fellow at Stanford University.

Jessilyn DunnDunn received her PhD in biomedical engineering from the Georgia Institute of Technology and Emory University and her bachelor’s degree in biomedical engineering from Johns Hopkins University. During that time, she studied the transcriptome and the epigenome of certain types of vascular cells to understand how these cells changed during disease processes.

With research centered on using large-scale biomedical data sets to predict health outcomes and design personalized interventions, Dunn will contribute to the growing focus on biomedical and health data sciences at Duke.

A major focus of the Dunn Lab will be generating predictive models for different diseases using statistical and machine learning methods, with the ultimate goal of developing effective and customized treatment plans tailored to individual patients. She will aim to draw novel health insights and actionable conclusions by integrating data from three sources: wearable devices, electronic health records, and multi-omics. Thus far, Dunn has focused her research on two areas: cardiometabolic disease and pre-term birth and pregnancy.

Dunn is a reviewer for multiple publications including the Journal of Biomedical Informatics and multiple IEEE publications and serves as managing editor of the Journal of Biomedical and Health Informatics. She is a member of the Institute of Electrical and Electronics Engineers (Engineering in Medicine and Biology Society), the American Medical Informatics Association, the Biomedical Engineering Society, and the American Heart Association.

The past, present, and future of IPF research at the DCRI

January 15, 2019 – The DCRI has been on the forefront of research into the chronic and fatal lung disease.

Little is known about the cause of idiopathic pulmonary fibrosis (IPF), a devastating disease that is characterized by progressive scarring of the lung tissue that affects a person’s ability to breathe and leads to death within three to five years of onset.  However, a team of respiratory medicine researchers at the DCRI is working to advance understanding of the deadly disease across the translational and clinical research spectrum.

The DCRI has been making strides in IPF research since 2005, when it became the coordinating center for IPFnet, a network of 26 clinical sites that was designed to conduct multiple clinical trials in the IPF space. Kevin Anstrom, PhD, director of biostatistics for the DCRI, was the principal investigator for IPFnet’s data coordinating center until 2014 and designed the clinical trials conducted within the network.

“IPFnet as a whole really changed the field and benefited everyone, including patients,” Anstrom said. “It not only cleared the way for other treatments to be introduced to market, but it also removed toxic therapies and gave patients more choice for their treatment.”

IPFnet helped set the stage for further research, Anstrom said; for example, many of the same clinical sites and investigators involved in IPFnet are now involved in the DCRI’s ongoing IPF-PRO registry.

Gaining Perspective

The IPF-PRO registry, which began in 2014 when the DCRI partnered with Boehringer-Ingelheim, follows patients with IPF for at least three years. Scott Palmer, MD, MHS, (pictured left) director of respiratory research at the DCRI and principal investigator for IPF-PRO, works on the registry along with the other members of the IPF-PRO team, which includes Laurie Snyder, MD, MHS; Jamie Todd, MD; Megan Neely, PhD; Eric Yow, MS; Emily Obrien, PhD; and Rosalia Blanco.

The IPF-PRO registry recently hit a milestone when it reached its goal of enrolling 1,000 patients. Although work with the registry continues, it has already resulted in 28 papers, abstracts, or presentations. As patients are followed out to longer time points, the study will provide increased ability to identify clinical factors and biomarkers that predict disease progression. In addition, the study captures information regarding the impact of the disease upon patient quality of life and will help clinicians and patients better understand the full impact of the disease and its treatment on patient-centered outcomes.

The team has also received funding to begin work on the second phase of the project. Concurrently with IPF-PRO, DCRI researchers will launch a parallel study called Interstitial Lung Disease-PROspective Outcomes (ILD-PRO), which will enroll non-IPF patients with interstitial lung disease (ILD). Boehringer-Ingelheim will also fund the new study and has committed $15 million, which will carry the study through 2025.

The study will focus on non-IPF patients, whose diseases are not considered “idiopathic” because a cause for the fibrosis has been identified. Even though they do not have IPF, some non-IPF ILD patients develop a progressive phenotype that mirrors IPF, Palmer said.

ILD-PRO will enroll these newly progressive patients and study patient data in much the same way as IPF-PRO in an attempt to understand the impact on patients’ quality of life, predictors of survival, and disease progression. All of the 47 active clinical sites that participate in IPF-PRO will also participate in ILD-PRO.

“It’s building upon what we already did (with IPF-PRO) and leveraging the collegial relationships we have with everybody involved,” Palmer said. “The beauty of having these two parallel studies is investigators can compare and contrast clinical factors and biological factors across interstitial lung disease, between IPF and what’s classified as non-IPF ILD to understand their underlying similarities and differences.”

A Genetic Link

The IPF-PRO registry also includes a biorepository of blood samples collected from patients, including DNA, RNA, serum, and plasma. This material, which was collected at patient enrollment and then at approximately six month intervals, will allow researchers to better understand biomarkers of IPF and how they are linked to IPF progression, said Jamie Todd, MD, co-chair of the IPF-PRO biomarkers committee.

“Right now, there are no FDA-approved biomarkers that could help clinicians with diagnosis and prognosis for IPF, so we are currently in a discovery phase with an ultimate goal of identifying some of those biomarkers,” Todd said. “In addition, because there are two relatively new treatments that have come onto the market since 2014, we may be able to identify biomarkers that indicate response to treatment.”

Because the team needed a control group to compare to the IPF population, it partnered with another study called the MURDOCK Study to identify a group of people who did not have lung disease.

Now, Todd said, the team is not only able to make comparisons among individuals with IPF, but can also understand what differences appear between a healthy person and a person with the disease. They have already found at least 40 proteins that significantly differ between the IPF population and the healthy population. Protein analyses within the IPF population could also help inform whether certain proteins correlate to disease severity and progression.

With the launch of ILD-PRO, the team will be following the same process to build a new biorepository with the ILD patient samples. Once the ILD repository is built, Todd hopes to compare the material to both the IPF and healthy repositories and conduct similar analyses. If biomarkers can help to understand disease mechanisms, she said, they can also assist in developing better treatments.

Todd (pictured right) also sees other potential uses for the genetic material, such as applying novel genome sequencing technology.

“Before IPF-PRO, there was no large, multicenter IPF biorepository in the United States,” Todd said. “This biorepository distinguishes IPF-PRO from other ongoing IPF registries in the U.S. and abroad. Now that the infrastructure exists, there are many opportunities for us to do some high-end, translational science in partnership with BI and our IPF-PRO site investigators.”

Changing the Game

In addition to the studies, the DCRI is also running NHLBI-funded clinical trials in the IPF space.

Anstrom is currently working on a trial he designed, CleanUP IPF.

The trial, which will enroll 500 patients and become the largest randomized study in the IPF space, seeks to determine whether two antibiotics, co-trimoxazole and doxycycline, help improve IPF outcomes. Both drugs will be tested against standard care.

“This type of high-dose treatment of antibiotics isn’t targeted at the fibrosis; rather, it’s used to prevent infections that could create other problems for IPF patients,” Anstrom said. “Previous literature suggests this approach has been helpful in cancer and other diseases. It would be valuable if it could also be applied to IPF because these therapies are affordable. The two treatments currently on the market are expensive, and there is no evidence that they reduce mortality.”

Each of these studies will benefit from the years of IPF research conducted by the DCRI. This community of researchers, Palmer said, has helped advance the state of IPF science. Another important component, he said, is that the DCRI’s clinical faculty on the IPF studies are physician investigators who treat people with IPF.

“I’m a physician, so I see patients with IPF every week, take care of them, and recognize the tremendous unmet needs associated with the disease,” Palmer said. “IPF research is a wonderful example of the strengths of the collaborative team at the DCRI. Our projects span from outcome registries to trials and include clinical and biostatistics faculty as primary investigators. We have built a network of really well-aligned investigators who care about IPF and about doing multi-center clinical research to move the field forward.”