The Implementing GeNomics In practice (IGNITE) Pragmatic Clinical Trials Network is an NIH-funded network dedicated to supporting the implementation of genomics in healthcare.

Effective January 2022, Christina Wyatt, MD, associate professor of medicine (Nephrology) and Scott Palmer, MD, MHS, professor of medicine (Pulmonary, Allergy, and Critical Care Medicine) will replace Geoff Ginsburg, MD, PhD, as principal investigators for the IGNITE Pragmatic Clinical Trials Network coordinating center. Ginsburg recently was announced as the National Institutes of Health (NIH) Chief Medical and Scientific Officer for the All of Us research program.

Dr. Wyatt and Dr. Palmer will join Hrishikesh Chakraborty, DrPH, to serve as joint principal investigators for Duke University, who is the coordinating center for IGNITE.

The IGNITE network is comprised of five research sites, a coordinating center, a steering committee and working groups, with oversight from The National Human Genome Research Institute (NHGRI)

Two genome medicine studies are currently being facilitated through IGNITE:

• ADOPT PGx is an umbrella protocol for three pragmatic clinical trials investigating pharmacogenomics (PGx)-guided therapy for acute post-surgical pain, chronic pain, and depression. Pain and depression impact substantial proportions of the U.S. population, but finding safe, effective drug therapies remains challenging.
• GUARDD-US is a pragmatic clinical trial that aims to determine the effect of returning apolipoprotein L1 (APOL1) genetic risk information to hypertensive African ancestry patients and their primary care providers, with a focus on the control of systolic blood pressure.

These trials aim to help researchers and clinicians understand what to expect with the return of genetic information to patients and providers in real-world clinical settings.

Learn more about the IGNITE network here

Read recent publications on IGNITE here

About the PIs:

Dr. Christina Wyatt is Associate Professor of Medicine and a core faculty member at the Duke Clinical Research Institute. She is a clinical-translational investigator at the intersection of HIV and kidney disease, including the role of genetic susceptibility attributed to variants in APOL1. Dr. Wyatt is currently the Clinical Core Director for a multidisciplinary P01 investigating the pathogenesis of HIV-related kidney disease, the PI of an ancillary study focused on kidney disease outcomes in the START clinical trial, and a co-investigator on 5 other NIH projects including a pragmatic clinical trial in young women using concomitant hormonal contraception and HIV pre-exposure prophylaxis. In addition to serving as PI or co-investigator on ancillary studies to the START and REPRIEVE clinical trials in people with HIV, Dr. Wyatt has experience as a member of Data and Safety Monitoring Boards and Clinical Endpoint Committees for large randomized clinical trials. She is an Associate Editor of Kidney International, the highest impact journal in nephrology, and a member of the Executive Committee for Kidney Disease | Improving Global Outcomes, the leading international guidelines organization in nephrology.

Dr. Scott Palmer is Vice Chair of Research for the Department of Medicine and Therapeutic Area for MedicinePlus at the Duke Clinical Research Institute. Dr. Palmer is clinically trained in pulmonary and critical care medicine and completed advanced training in clinical research completing an MHS degree. He brings over 20 years of NIH funded research expertise including in translational human genetics and extensive experience leading successful multicenter consortium. He has led a high impact prospective, randomized, double-blind, placebo-controlled multicenter study to prevent CMV infection after lung transplant, published in Annals of Internal Medicine. He also led as PI and coordinated through the DCRI a phase 2 multicenter study of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist, that established the proof-of-concept efficacy of this class of agents for the treatment of Idiopathic pulmonary fibrosis (IPF). He led administrative coordinating center (ACC) the multicenter Lung Regeneration and Repair Consortium (LRRC) and served as MPI for the Data Coordinating Center (DCC) of the Molecular Atlas of Lung Development (LungMAP), phase 1. He currently leads as overall study PI an ongoing 50-site IPF and ILD registry (IPF-PRO/ILD-PRO) that has enrolled over 1,500 patients with IPF or ILD. He also created and led as PI the first dedicated adult lung transplant NIAID Clinical Trials in Organ Transplant (CTOT) consortium. His notable genetic studies include the identification of rare protein coding variants in telomerase related genes that underlie the development of sporadic IPF.

Dr. Hrishikesh Chakraborty is the Associate Professor in the Department of Biostatistics and Bioinformatics, Director of Pragmatic Clinical Trial Biostatistics at the Duke Clinical Research Institute, and Co-Director of the Quantitative Sciences Core for the Center for AIDS Research (CFAR) at Duke University. Currently, he is the principal investigator (PI) for (1) IGNITE Network Coordinating Centers (CC), (2) The Biomarkers of dietary intake and exposure Consortium CC, (3) Health care systems to move guideline-based care of low back pain Data Coordinating Center (DCC), (4) Mono- vs. Duo-therapy for pediatric pulmonary arterial hypertension DCC, (5) TRANSFORM-HF trial of torsemide compare with furosemide DCC, and (6) SPIRRIT-HFPEF pragmatic, registry-based randomized clinical trial that evaluate the clinical effectiveness of spironolactone versus usual care DCC. He has served as PI, co-PI, co-Investigator, and statistical investigator for large, single, and multicenter pragmatic clinical trials, observational studies, cohort studies, cluster randomized studies, CCs, DCCs, and implementation studies. He has independent, collaborative, and consulting research experience in biostatistics, public health, biomedical, clinical, epidemiologic, and social science research, and has worked in several different therapeutic areas including HIV/AIDS and other infectious diseases, maternal and child health, and cardiology/vascular diseases. He has been involved in complex and innovative clinical trials and implementation studies and has over 25 years’ expertise in collaborative single and multi-site trial management, study design, sample size calculation, data management, data quality control, data analysis, report writing, and publication of results.

The IGNITE Network Leadership calls for Diversity and Inclusion in the conduct of research

We call on scientific and medical communities to acknowledge and work toward eliminating the injustices perpetuated through all forms of systemic racism and discrimination, both past and present, overt and covert. We condemn eugenic beliefs, policies, and practices. While ancestry has some genetic underpinnings, race is a social construct. Thus, we recognize the consequences of racism and bias on health, healthcare, and research.

To provide more equitable care and improve health for all communities, researchers must investigate and address the causes of health disparities and include more diverse people as study leaders and participants. We commit to working hand-in-hand with patients and advocates from underserved communities to ensure that research is performed, published and applied in an ethical, unbiased, trustworthy and inclusive manner.

Striving for an equitable future, we endorse anti-racist and anti-discriminatory policies in healthcare and research. To develop a culture of understanding and inclusiveness that extends to the diverse communities we are privileged to serve, we must also foster diversity in our own institutions.

This statement and the actions that follow are the foundations of a durable process in the pursuit of health equity.

Getting diagnosed with a disease can be scary. Health providers work to find the right treatment plan based on the current standard of care guidelines. But what if in addition to the current evidence, doctors could also factor in each patient’s unique genetic makeup to help them diagnose more quickly and accurately, create a tailored treatment plan, or better yet, learn which patients are at a higher risk for developing specific diseases and employ methods for prevention or earlier detection? That’s the hope of genomic medicine, but researchers and clinicians are still gathering more evidence of its effectiveness before it can be widely implemented.

The IGNITE Network is looking to provide some of that evidence. The Network is comprised of a coordinating center and five multi-site clinical groups from Duke, Mt. Sinai, Vanderbilt, University of Indiana and University of Florida.

In order to provide the evidence that this type of practice will improve patient outcomes, IGNITE is conducting two large, network-wide genomic medicine pragmatic clinical trials (PCTs). These PCTs are focused around genetic risks for common chronic diseases and pharmacogenomics. PCTs are different than randomized controlled trials, or RCTs, which are great for studying the effectiveness of a treatment, but PCTs allow for bigger, more efficient clinical trials and help researchers and clinicians understand what to expect in real-world clinical settings.

Genetic testing to Understand Renal Disease Disparities across the U.S. (GUARDD-US) is a PCT that aims to determine the effect of returning apolipoprotein L1 (APOL1) genetic risk information to hypertensive African ancestry patients and their primary care providers on systolic blood pressure (SBP). The primary outcome is SBP at three months comparing patients with high-risk APOL1 variants (positives) versus no high-risk variants (negatives). The co-primary outcome is three-month SBP in positives versus those receiving delayed testing. Secondary outcomes include renal disease testing, and psycho-behavioral factors. The team will re-randomize APOL1 negative patients to a genotype-guided approach to anti-hypertensive therapy versus usual care and compare three-month SBP.

A Depression and Opioid Pragmatic Trial in Pharmacogenomics (ADOPT PGx) is a pragmatic clinical trial that enrolls patients into three pharmacogenomics (PGx)-guided therapy scenarios: acute post-surgical pain, chronic pain, and depression. For each scenario, participants will be randomized to genotype-guided drug therapy versus usual approaches to drug therapy selection (“usual care”). Changes in patient-reported outcomes representing pain and depression control using standard patient-reported outcomes measurement information system (PROMIS) scales define the primary endpoints. Secondary analyses include safety endpoints, changes in overall well-being, and economic impact represented by differences in healthcare utilization.

Both GUARD-US and ADOPT PGx teams will begin recruiting people for the PCTs in mid to late 2020.

The IGNITE Network has the potential to drastically change the face of healthcare. As results from the PCTS come in, clinicians all over the world may be able to see the clinical utility of genomic medicine for both risk assessment and disease treatment.

Members of the IGNITE Network were involved in three of the five publications in this series. Genomic Medicine 1: Opportunities, resources and techniques for implementing genomics in clinical care describes the major types and measurement tools of genomic variation that are currently of clinical importance, reviews approaches to interpreting genomic sequence variants, identifies publicly available tools and resources for genomic test interpretation, and discusses several key barriers in using genomic information in routine clinical practice. Genomic Medicine 4: Family health history: Underused for actionable risk assessment discusses the importance of family health history as a tool for risk assessment for common chronic diseases. Genomic Medicine 5: Building evidence and measuring clinical outcomes for genomic medicine reviews clinical outcome studies in genomic medicine and discusses the important features and key challenges to building evidence for next generation sequencing in the context of routine patient care.

The National Institutes of Health will fund clinical trials to assess the benefits, applicability and efficacy of applying genomic medicine interventions to improve management of diseases such as high blood pressure, depression and chronic pain. The trials are part of the second phase of the Implementing Genomics in Practice (IGNITE) Network with a total investment of $42 million over five years, pending the availability of funds. The trials will begin in 2020. Read more

The Implementing Genomic in Practice (IGNITE) Network was established in 2013 (RFA-HG-12-006, RFA-HG-12-007 and RFA-HG-13-004) to develop methods for incorporating genomic information into clinical care and explore the methods for effective implementation, diffusion, and sustainability in diverse clinical settings. The first phase of the network, IGNITE I, was a consortium of collaborative genomic medicine pilot Demonstration Projects designed to demonstrate the feasibility of, and develop methods for, incorporating an individual patient’s genomic findings into his or her clinical care.

The next phase of IGNITE, IGNITE II (RFA-HG-17-008, RFA-HG-17-009, and RFA-HG-17-010) will support a network of multi-site Clinical Groups (CGs) involving diverse settings and populations to conduct 2-3 pragmatic clinical trials of genomic medicine interventions.

Read full overview from NIH