Clinical Trials on a Chip

Many individuals suffer from difficult-to-treat, life-threatening diseases, including specific types of cancers, neurological disorders, and pediatric and rare diseases. For these individuals, clinical trials are an important strategy to finding effective new and repurposed therapies. Unfortunately, around 85 percent of late-stage clinical trials of investigational drugs fail because of safety problems or ineffectiveness, despite promising preclinical test results in conventional models, such as 2D cell culture systems, and animal models, such as mice. Moreover, certain diseases, such as rare disorders or pediatric conditions, are not adequately represented in clinical trials or do not have the resources to conduct them.

To improve the rate of success of new therapeutics in drug development, NCATS has awarded 10 inaugural grants to support researchers’ efforts in creating microphysiological, bioengineered models of human tissues and organ systems to inform clinical trial design for both common and rare diseases. In addition to helping inform clinical trial design, these projects also will support the planning and execution of clinical trials, assist in patient stratification, help identify reliable clinical trial endpoints, and ultimately develop tools for more informative and efficient clinical trials for both common and rare diseases.

The awards are administered through a new program, “Clinical Trials” on a Chip, which is led by NCATS, in conjunction with several other NIH Institutes and Centers.

These awards were made in response to RFA-TR-19-014.

View the project details below:

Boston Children’s Hospital

Tissue Chips for Precision Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia

Principal Investigators: William Pu, M.D. (Harvard Medical School), and Kevin Kit Parker, Ph.D. (Harvard University)

Grant Number: 1-UG3-TR-003279-01

Clinical trials for rare diseases may expose patients to risk and fail to identify subsets of patients who may benefit from specific therapies. Patient-specific approaches based on tissue chips could reduce trial risk, sharpen patient selection and explain patient variations in treatment response. Researchers will create tissue chips using individual patients’ induced pluripotent stem cells to predict responses to therapies for a rare inherited arrhythmia, catecholaminergic polymorphic ventricular tachycardia (CPVT). The chip will assess individual patients’ arrhythmia risk and examine the link between genotypes and response to therapies. The project will test whether personalized disease models on a chip can predict CPVT patients’ treatment responses in clinical trials.

Learn more about this project in NIH RePORTER.

*Funded by NCATS with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Brigham and Women’s Hospital

“Clinical Trials” on a Premature Vascular Aging-on-a-Chip Model

Principal Investigator: Yu-Shrike Zhang, Ph.D. (Harvard Medical School)

Grant Number: 1-UG3-TR-003274-01

The cardiovascular system is a major organ affected in Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder that causes premature and accelerated aging. Large arteries, such as the aorta and carotid arteries, often lose vascular smooth muscle cells. This project will develop an HGPS-on-a-chip system from patient-derived fibroblasts, smooth muscle cells and endothelial cells. The design will recreate the microenvironment of blood vessels to assess pathological changes caused by HGPS and help researchers shape clinical trials for rare diseases, such as HGPS.

Learn more about this project in NIH RePORTER.

*Funded by NCATS.


A Microphysiological Multicellular Organ-on-Chip to Inform Clinical Trials in FTD/ALS

Principal Investigator: Clive Niels Svendsen, Ph.D.

Grant Number: 1-UG3-TR-003264-01

The neurodegenerative diseases frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) currently have no viable treatments. FTD and ALS share key clinical, pathological and genetic characteristics. Models of FTD/ALS are being used to identify biomarkers useful in preclinical testing of potential treatments, as well as to stratify patients when designing clinical trials. This project will develop a three-dimensional platform that includes cortical neurons, astrocytes, microglia and a blood-brain barrier component. The chip will model the forebrain in FTD/ALS and allow researchers to assess patients’ cellular responses to five therapies that are entering early phase clinical trials.

Learn more about this project in NIH RePORTER.

*Funded by NCATS.

Columbia University

Clinical Trials in a Dish Using a Personalized Multi-Tissue Platform for Atopic Dermatitis*

Principal Investigator: Angela M. Christiano, Ph.D.

Grant Number: 1-UG3-AR-079297-01

Atopic dermatitis (AD) is a multifactorial disease. Multi-tissue microphysiological systems are needed to study the interaction between skin, corneal and nasal tissues; immune system T cells; and the microbiota (Sk-Co-Na-T-MB). This project will reproduce the Sk-Co-Na-T-MB model on a chip. Researchers will develop and study microphysiological systems composed of stem cells taken from both healthy donors and donors with AD. The team will then compare the two groups’ responses to U.S. Food and Drug Administration-approved drugs to find potential therapeutics for the treatment of AD.

Learn more about this project in the NIH RePORTER.

*Funded by NCATS, with additional funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Johns Hopkins University

Engineering Clinical Trials on a Chip for Dystrophin-Deficient Muscular Dystrophy*

Principal Investigators: Deok-Ho Kim, Ph.D., and David Alan Kass, M.D.

Grant Number: 1-UG3-TR-003271-01

New therapies are needed for the treatment of Duchenne and Becker types of dystrophin-deficient muscular dystrophy (DMD/BMD). Better in vitro tools can help researchers understand how these genetic diseases affect cardiac and skeletal muscle tissues, and they can speed development of new therapies. This project will develop 3-D engineered muscular tissues to explore cardiac and skeletal muscle deficiencies in DMD/BMD and test potential therapies. The chip platform will allow real-time assessment of drug treatment efficacy. The researchers will use the platform to simulate protocols for running a Phase 3–style clinical trial of a new cation-channel inhibitor.

Learn more about this project in NIH RePORTER.

*Funded by NCATS with additional funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Texas A&M Engineering Experiment Station

Developing Extracellular Vesicle–Based Therapeutics Against Preterm Birth Through the Use of Maternal-Fetal Interface on a Chip*

Principal Investigators: Arum Han, Ph.D. (Texas A&M University), and Ramkumar Menon, Ph.D. (The University of Texas)

Grant Number: 1-UG3-TR-003283-01

Fetal immune responses are a key mediator triggering spontaneous preterm birth, but current prevention strategies do not address these responses. Reducing inflammation in the tissues at the fetal-maternal interface could help maintain pregnancy and prevent spontaneous preterm birth. This project will develop an organ-on-chip model that reproduces the structure, function and responses of the fetal-maternal tissue interface. The chip will recreate healthy and inflammatory conditions and allow testing of a compound that inhibits the immune regulator NF-kB. The organ-on-chip could offer a personalized fetal-maternal interface model to test potential treatments and streamline clinical trials.

Learn more about this project in NIH RePORTER.

*Funded by NCATS with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

University of Pittsburgh

A Vascularized, Patient-Derived iPSC Liver Acinus Microphysiological System as an Innovative Precision Medicine Platform for Optimizing Clinical Trial Design for Nonalcoholic Fatty Liver Disease

Principal Investigators: D. Lansing Taylor, Ph.D., Jaideep Behari, M.D., Ph.D., and Alejandro Soto-Gutierrez, M.D., Ph.D.

Grant Number: I-UG3-TR-003289-01

No approved treatments exist for nonalcoholic fatty liver disease (NAFLD), which can progress to nonalcoholic steatohepatitis, cirrhosis and liver cancer. Better preclinical drug testing models are needed that reflect the spectrum of phenotypes and risk factors in humans. Researchers will use patient-specific vascularized liver tissue chips to test NAFLD patients’ responses to multiple treatment options. The project will compare the responses of normal and high-risk patient groups to two NAFLD drugs and two control drugs. The approach could improve clinical trials by identifying NAFLD patient groups most likely to benefit from a treatment.

Learn more about this project in NIH RePORTER.

*Funded by NCATS.

University of Rochester

A Microphysiological System of Tendon Inflammation and Fibrosis for Drug Screening and Efficacy Testing*

Principal Investigators: Hani A. Awad, Ph.D., James L. McGrath, Ph.D., and Benjamin L. Miller, Ph.D.

Grant Number: 1-UG3-TR-003281-01

Fibrotic scarring damages injured tendons and can impair joint function. In a fibrotic tendon scar, signaling between inflammatory cells and tendon fibroblasts can lead to fibrosis. This project will develop a human tendon-on-chip system to model the inflammation and fibrosis in injured tendons. To simulate signaling between fibroblasts, macrophages and endothelial cells, the system will feature a design with tendon fibroblasts, an endothelial barrier and microfluidic channels to simulate vascular blood flow. The chip will include photonic sensors to allow real-time on-chip sensing. The system will explore the role of the growth-regulating mTOR pathway in fibrotic tendon scars, identify biomarkers, and test both mTOR inhibitors and other compounds as potential therapies for tendon injury.

Learn more about this project in NIH RePORTER.

*Funded by NCATS with additional funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

University of Washington

Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological Systems

Principal Investigators: Jonathan Himmelfarb, M.D. (University of Washington), and Matthias Kretzler, M.D. (University of Michigan)

Grant Number:1-UG3-TR-003288-01

The kidney’s structural and functional complexity contributes to a relative lack of successful clinical trials for kidney diseases. Models are needed that recreate key elements of kidney physiology, such as specific nephron segments to assess their responses to injury. This project will create patient-specific human-kidney-on-a-chip devices to explore how patients’ in vitro responses align with their in vivo clinical trial outcomes. The chips will include stem cells from patients with two kidney diseases with genetic components, focal segmental glomerulosclerosis and polycystic kidney disease. The researchers will examine how individuals’ genetic differences affect clinical responses. Understanding patient-specific molecular and cellular responses could lead to effective precision medicine treatments for kidney diseases.

Learn more about this project in NIH RePORTER.

*Funded by NCATS.

University of Wisconsin–Madison

Mechanisms of Microenvironment-Mediated Resistance to Cancer Cell–Surface Targeted Therapeutics*

Principal Investigators: David J. Beebe, Ph.D., and Joshua Michael Lang, M.D. 

Grant Number: 1-UG3-TR-003280-01

Prescreening models for oncology drugs do not adequately replicate actual patient physiology, often leading to failed clinical trials. Clinical prescreening models should include the highly complex tumor microenvironment (TME), with its multiple cell types and vasculature. To test potential therapies for metastatic castrate-resistant prostate cancer, this project will build a tissue chip that models the bone marrow microenvironment. The chip will feature patient-derived prostate tumor spheroids surrounded by bone marrow stromal cells, immune cells and endothelial cell vasculature. Researchers will be able to study multiple cell-surface targeted therapies, enhancing our understanding of TME-induced treatment resistance and helping to better stratify patients to improve clinical trial efficiency.

Learn more about this project in NIH RePORTER.

*Funded by the National Cancer Institute with additional funding from NCATS.