Specialized procedures are often needed to measure outcomes in cystic fibrosis clinical trials, including laboratory-based measurements, such as sweat chloride, microbiologic endpoints, and biomarkers; and interpretive outcomes, such as multiple breath washout/lung clearance index and nasal potential difference.
Most National Resource Centers (NRCs) fit into one of two frameworks: Service Cores are typically established centers or networks that provide centralized and standardized assays or outcome measures relevant to CF translational and clinical research; and other centers are focused on outcome measure advancement and seek to develop and validate new outcome measures relevant to CF clinical research.
Specialized Services
Personnel at each NRC are available to consult with study sponsors and investigators about the use of these specialized CF outcome measures and provide related support for specific studies (including for pre-clinical and translational research).
Services offered may include, but are not limited to:
- Performance of central testing, interpretation, and/or data analysis
- Assistance with selection of appropriate CF outcome measures
- Consultation on outcome measure implementation
- Assistance selecting and evaluating contract research organizations, both academic and commercial
- Training, qualification, and ongoing support of study site operators
Contacting the NRCs early in the study development process can help make study setup more efficient and ensure more timely and cost-effective completion of studies.
For more information about specific services, contact the center personnel listed below.
NRC Cores
Advancement of the Center for CFTR Detection
The Advancement of the Center for CFTR Detection (CCD) to support CF therapeutic development specializes in the development and upkeep of harmonized standard operating procedures (SOPs), training, performance, and interpretation of nasal potential difference traces and other measures of CFTR detection in CF clinical trials.
The CCD has been a key resource in the standardization and training in potential difference (PD) measurements. Through extensive experience with clinical research, the CCD has established algorithms that make multi-center data collection feasible for recent and ongoing therapeutic trials. Finally, the center supports referrals for collections and bioreposition of clinical tissue samples from people with CF with rare and other CFTR variants to support pre-clinical development of nucleic acid-based therapies (NABT).
Site: University of Alabama at Birmingham
Director:
George M. Solomon, M.D.
gsolomon@uab.edu
Other Personnel:
Kay Vijaykumar, MD, Associate Director
kvijaykumar@uabmc.edu
Heather Hathorne, PhD
hyhathorne@uabmc.edu
Justin Anderson, MS
justinanderson@uabmc.edu
Center for Biochemical Markers
The Center for Biochemical Markers NRC provides expertise in the measurement of biomarkers of inflammation and lung disease; biomarkers of liver and pancreatic disease; growth hormone measurements; and measures of nutritional status, including vitamin and antioxidant levels, in blood, sputum, bronchoalveolar lavage fluid, stool, and urine.
Inflammatory biomarker data generated by this NRC have been used to screen anti-inflammatory candidates for biologic activity, establish proof-of-concept, and help inform early go/no-go decisions in CF drug development. Our vision is that this NRC will continue to provide our unique core services to investigators nationwide and multinational pharmaceutical companies looking to develop new treatments for CF.
Site: Children's Hospital Colorado and University of Colorado Anschutz Medical Campus
Director:
Scott D. Sagel, MD, PhD
scott.sagel@childrenscolorado.org
Other Personnel:
Rebecca Baldermann, Laboratory Manager
rebecca.baldermann@childrenscolorado.org
Center for Sweat Analysis
The Center for Sweat Analysis offers expertise in the collection and analysis of sweat electrolytes, an outcome measure of CFTR protein function in CF clinical studies. The primary aims of the center are to:
- Standardize sweat collection and analysis through development and dissemination of standardized operating procedures
- Serve as a central laboratory for measuring sweat electrolytes as a CFTR-related outcome measure in CF clinical studies
- Train and certify site personnel in the proper performance of sweat collection
- Provide consultative services to investigators and industries interested in sweat measurements for research
In addition, the center offers expert consultation and training to CF care centers with high levels of quantity-not-sufficient samples or other issues with sweat collection for the diagnosis of CF.
Site: Children's Hospital Colorado and University of Colorado Anschutz Medical Campus
Director:
Edith Zemanick, MD, MSCS
edith.zemanick@childrenscolorado.org
Other Personnel:
Mary Cross
mary.cross@childrenscolorado.org
Colorado NTM Core Clinical Research Service NRC
This NRC consists of investigators and laboratories with unique skills and knowledge in studying nontuberculous mycobacteria (NTM). Their goal is to provide technical support to studies that aim to improve the diagnosis and treatment of NTM in CF. This NRC offers expertise in clinical study design, sample collection, specialized testing and banking of NTM, as well as a range of research tools that are needed to support and improve the success of clinical trials focused on this infection.
Site: National Jewish Health, Denver
Director:
Jerry Nick, MD
nickj@njhealth.org
Other personnel:
Charles Daley, MD
daleyc@njhealth.org
Colorado NTM Outcome Measure Advancement Core NRC
This NRC consists of investigators and laboratories with unique skills and knowledge in studying NTM. The goal of this core is to better understand NTM and to improve its diagnosis and treatment in CF. The NRC will advance innovative techniques and new technologies that bypass the current limitations of sputum cultures, which are insensitive and increasingly difficult to obtain.
Services include consultation on preclinical NTM therapeutic development, provision of CF NTM isolates, in vitro testing of candidate antibiotics on well-characterized CF NTM isolates, novel models of NTM infection, analyses of NTM whole genome sequencing databases, protein structural modeling, quantitation of NTM in samples, phylogenetic analysis of NTM isolates, biomarker development, pharmacokinetics/pharmacodynamics assays of sputum, and associated training of these techniques to qualified investigators and trainees.
Site: National Jewish Health, Denver
Director:
Jerry Nick, MD
nickj@njhealth.org
Other personnel:
Charles Daley, MD
daleyc@njhealth.org
From Colorado State University:
Miriam Braunstein, PhD
miriam.braunstein@colostate.edu
Delphi Chatterjee, PhD
delphi.chatterjee@colostate.edu
Mercedes Gonzalez-Juarrero, PhD
mercedes.gonzalez-juarrero@colostate.edu
Marcela Henao-Tamayo, MD, PhD
marcela.henao_tamayo@colostate.edu
Mary Jackson, PhD
mary.jackson@colostate.edu
Andres Obregon, PhD
andres.obregon@colostate.edu
Cystic Fibrosis Microbiological Outcomes Advancement Core
This NRC develops and provides special and clinically relevant microbiological tests and resources for CF research and therapeutics development, including clinical specimens and microbial isolates, uncommon culture media and conditions, and molecular (DNA-based) microbiological identification and quantitation.
For the past five years, this NRC has served as a repository of the specimens and isolates collected by CF studies, as a facility that performs existing, nonstandard tests (such as in vitro susceptibility testing for new candidate treatments and sputum inactivation of drugs), and as a laboratory that develops new approaches and resources and performs new tests, such as DNA-based analyses.
Site: University of Washington, Seattle
Directors:
Lucas Hoffman, MD, PhD
lhoffm@uw.edu
Rafael Hernandez, MD, PhD
rafael.hernandez@seattlechildrens.org
Other personnel:
Daniel Wolter, PhD, Technical Director
dwolter@uw.edu
Donna Prybell, Core Administrator
dprybell@uw.edu
Cystic Fibrosis Microbiome Analysis Core
The goal of the Cystic Fibrosis Microbiome Analysis Core is to facilitate best practices in microbiome research for the CF research community. The core has developed and will provide SOPs for all steps essential for microbiome analysis of CF clinical samples, including sample collection and processing, bioinformatics, and biostatistics. In addition, they will provide expert consulting and training in all phases of microbiome-based CF projects.
Site: Children's Hospital Colorado and University of Colorado School of Medicine
Director:
Brandie Wagner, PhD
brandiewagner@cuanschutz.edu
Other personnel:
Kirk Harris, PhD
jonathan.harris@cuanschutz.edu
Nasal Cell Theratyping Advancement Core
The Cincinnati Children's Hospital Nasal Cell Culture Core for Outcome Measure Advancement focuses on optimizing and advancing laboratory models based on human nasal cells and provides personalized cell-based CFTR modulator drug testing, culture and analysis for studies of nucleic acid-based therapies, and protocol and regulatory support for translational clinical care and CF-focused research. The overarching goal of this core is to establish and validate a national system for collection and testing of human nasal epithelial cell-based models to support translational CF clinical care and research trials.
Site: Cincinnati Children's Hospital Medical Center
Director:
John Brewington, MD
john.brewington@cchmc.org
Other personnel:
Georgia Kelly
georgia.kelly@cchmc.org
SCRI Center for CF Microbiology
The Center for CF Microbiology provides best-practice CF clinical laboratory microbiological services and consultation to develop and support CF clinical trials. The laboratory provides expertise in the isolation, quantitation, identification, and antibiotic-susceptibility testing of CF pathogens in respiratory tract samples. The center works to develop and validate laboratory methods, establish protocols for CF microbiology, and obtain high quality microbiology data for clinical trials.
Site: Seattle Children's Hospital
Director:
Lucas Hoffman, MD, PhD, Laboratory Director
lhoffm@uw.edu
Drew Bell, PhD, Co-Director
drew.bell@seattlechildrens.org
Other Personnel:
Anne Marie Buccat, MS, Technical Director
annemarie.buccat@seattlechildrens.org
Mucociliary Clearance NRC
This NRC supports the development and conduct of multicenter mucociliary clearance (MCC) studies by providing training and technological advances, disseminating expertise, and facilitating conduct of studies using the MCC endpoint. Service aims include continued standardization of methods, dissemination to new study sites, and continuous monitoring of procedures and data quality. Further, the MCC NRC will provide an expert source of consultation for industry and academic partners seeking to incorporate MCC measurement into new study protocols.
Site: The University of North Carolina at Chapel Hill
Director:
Scott Donaldson, MD
scott_donaldson@med.unc.edu
Multipronged Assessment of CFTR in Epithelial Tissues for Evaluating Nucleic Acid-Based Therapies
The Multipronged Assessment of CFTR in Epithelia (MACE) National Resource Center at the University of North Carolina at Chapel Hill assembled a multidisciplinary team with expertise in bronchoscopy, biobanking, CFTR imaging, and the analysis of CFTR mRNA, CFTR protein levels, maturation, and function. The MACE NRC develops and standardizes robust methodologies to quantify and localize functional CFTR in airway biospecimens, while also optimizing procedures for their handling, shipping, and storage.
This NRC will provide essential tools for evaluating NABT in clinical trials. The NRC has four aims focused on:
- Detecting mature CFTR protein
- Localizing CFTR in tissues via immunostaining
- Analyzing CFTR mRNA expression and distribution
- Measuring CFTR ion channel activity
The MACE NRC will support rigorous evaluations of NABT, speeding their development and approval to expand treatment options for all people with CF.
Site: University of North Carolina at Chapel Hill
Director:
Martina Gentzsch, PhD
gentzsch@med.unc.edu
Other Personnel:
Wanda O'Neal, PhD
wanda_o'neal@med.unc.edu
Kenichi Okuda, MD, PhD
ken_okuda@med.unc.edu
Deborah Cholon, PhD
deborah_cholon@med.unc.edu
North American Multiple Breath Washout Center
The Multiple Breath Washout (MBW) Resource Center supports the development and upkeep of SOPs, training, and interpretation of MBW/lung clearance index testing in CF clinical research. The program has developed online learning materials to train more operators to correctly perform the MBW test, as well as computer software that can determine whether an MBW test is done properly. This will enhance the conduct of future CF trials and also potentially translate the use of this lung function test for routine monitoring of lung function.
Site: The Hospital for Sick Children
Director:
Felix Ratjen, MD, PhD
felix.ratjen@sickkids.ca
Other personnel:
Renee Jensen
renee.jensen@sickkids.ca
Michelle Shaw
michelle.shaw@sickkids.ca
Pharmacokinetics and Pharmacodynamics Core
The pharmacokinetics (PK) and pharmacodynamics (PD) National Resource Center was developed to provide reliable, low cost PK/PD services to CF investigators worldwide to support drug development and optimization as well as evaluation of drug efficacy. The Center has established mass spectrometric (MS) methods to measure a large number of drugs and biomarkers, including all currently approved CFTR modulators, many other CF relevant drugs, and an extensive panel of metabolomic biomarkers of pathways involved in CF airways disease. Furthermore, the core has a robust and proven capacity to develop MS methods for novel therapeutic agents and small molecular biomarkers of interest to investigators.
The PK/PD NRC has utilized these methods to support clinical and pre-clinical studies from around the world and has multiple ongoing collaborations. Continued Cystic Fibrosis Foundation support will allow the center to continue providing this core of expertise to the CF research community. The core aims to assist clinical investigators interested in studying the factors that alter drug PK/PD in patient populations as well as pre-clinical investigators who need to better understand the PK/PD properties of therapeutics and biomarker assessments in model systems.
Site: The University of North Carolina at Chapel Hill
Director:
Charles Esther
charles_esther@med.unc.edu
Other personnel:
Tara Guhr Lee
taraguhr@email.unc.edu
