Rare Diseases Clinical Research Consortia (RDCRC) for the Rare Diseases Clinical Research Network

UPDATE: The ORD, in collaboration with other NIH Institutes, has released two RFAs for the recompetition of the RDCRN. In collaboration with NICHD, NINDS, NIAMS, NIDDK, NHLBI, National Cancer Institute (NCI), National Institute on Aging (NIA), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Dental and Craniofacial Research (NIDCR), ORD has issued RFA-OD-08-001, Rare Diseases Clinical Research Consortia (RDCRC) for the Rare Disease Clinical Research Network (U54) for the recompetition of funding for individual consortia. In collaboration with NINDS, ORD has released RFA-OD-08-002, Data Management and Coordinating Center (DMCC) for the Rare Diseases Clinical Research Network (U54), for the recompetition of funding for the data management center. The key deadlines for both RFAs are indicated in the table below.A pre-application meeting was Webcast on March 17, 2008.  Additional information relevant to the meeting, including links to the video archive, slides, and FAQs, can be found in the table below.

Background

Rare Diseases Clinical Research Network (RDCRN)

On February 27, 2003, ORD in response to the Rare Diseases Act of 2002, P.L. 107-280, released a Request for Applications (RFA) for a Rare Diseases Clinical Research Network together with the National Center for Research Resources (NCRR)/General Clinical Research Consortium (GCRC) Program and in collaboration with other NIH Institutes. ORD, NCRR, and the National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Heart, Lung, and Blood Institute (NHLBI), all components of the NIH, funded eight rare diseases clinical research consortia and one Data and Technology Coordinating Center.

Abstracts of the funded applications follow:

Description from the Grant Application:
We propose to establish a Rare Disease Clinical Research Consortium (RDCRC) at the Children's National Medical Center (CNMC) in Washington, DC. The RDCRC will draw support from both the Pediatric General Clinical Research Center at CNMC/Georgetown University Medical Center (GUMC) as well as its Mental Retardation and Developmental Disabilities Research Center (MRDDRC). The unifying clinical theme of the RDCRC is the study of urea cycle disorders (UCD). This RDCRC will consist of a network of five academic institutions, each of which has GCRC/MRDDRCs: CNMC/GUMC, Children's Hospital of Philadelphia, Vanderbilt University, Baylor Medical College, and University of California at Los Angeles. The proposed RDCRC will comprise a multidisciplinary team of 10 investigators in the following specialties: Genetics, Metabolism, Developmental Pediatrics, Clinical Pharmacology, Neurology, Psychology, Biostatistics, and Neuroimaging. Mark L. Batshaw, M.D., the Director of the CNMC MRDDRC, will serve as Principal Investigator

Description from the Grant Application:
This is an application from an inter-institutional group of investigators with long-standing interest in Rett syndrome, Angelman syndrome (AS), and Prader-Willi syndrome (PWS) to establish a Rare Diseases Clinical Research Consortium (RDCRC) that would be part of the proposed Rare Diseases Clinical Research Network (RDCRN). The consortium will focus on these three disorders with the expectation that they may have near-term potential for meaningful therapy. The specific aims for Rett will be to establish a phenotype/genotype correlation over a broad spectrum of Rett phenotypes, to perform longitudinal studies on a broad sample of individuals with Rett, and to perform a survival study on a broad spectrum of Rett individuals. Clinical trials may be developed based on results of studies of animal models. The specific aims for AS are to conduct a longitudinal assessment of patients with AS according to genotype, to complete the ongoing double-blind, placebo controlled trial of folic acid and betaine in AS, and to

Description from the Grant Application:
This application proposes to investigate three rare neurological channelopathies: periodic paralysis, non-dystrophic myotonic disorders, and episodic ataxia. The research plan will exploit the strengths of seven collaborating centers to link molecular scientists studying these disorders with clinical investigators with established expertise in the development of new treatments for neurological disease. It will extend a prototype NIH training program in experimental therapeutics to train a cadre of patient-oriented researchers committed to rare disorders. Study investigators have strong links with the patient advocacy organizations focused on these rare disorders: The Periodic Paralysis Association, the National Ataxia Foundation, and the Muscular Dystrophy Association. A particular strength of the collaborating institutions is an established nationwide infrastructure, including GCRCs and a biostatistician, for the implementation of multicenter clinical trials that will facilitate investigation of the efficacy

Description from the Grant Application:
Idiopathic bone marrow failure states and cytopenias (IBMFS&C) are rare disorders characterized by hematopoietic progenitor or stem cell failure resulting in deficient production of one, or all, blood cell lineages. Immune pathophysiology is a unifying factor in many cases of all these diseases. Prior collaborative trials have led to the improvement of effective medical therapy for aplastic anemia (AA), but ongoing multicenter studies are required to advance further the outcome for AA and especially the other bone IBMFS for which few useful treatment options exist. The IBMFS&C Rare Disease Clinical Research Consortium (RDCRC) at the Cleveland Clinic Foundation (CCF) Cancer Center will encompass a consortium of several specialized centers, patient advocacy group, data, and a collaboration with a data technology coordinating center (DTCC), the IBMFS&C RDCRC will focus on AA, paroxysmal nocturnal hemoglobinuria, single-lineage cytopenias including large granular lymphocyte leukemia and pure red cell aplasia, and

Description from the Grant Application:
Aim 1: Establish a multicenter Vasculitis Clinical Research Consortium (VCRC) to foster and facilitate clinical investigation in the inflammatory vasculitides. The four major U.S. vasculitis centers (Boston University, Cleveland Clinic, Johns Hopkins, and Mayo Clinic) will combine their clinical and research expertise with the resources of the General Clinical Research Centers at each site to form the core of the consortium. Additionally, the combined strengths of several domestic and foreign secondary centers will be incorporated into the consortium. The VCRC would serve as the focal point for vasculitis research in the United States and internationally for both clinical investigators and patients. To achieve this aim, the following activities are proposed:

• Develop a clinical data repository in collaboration with other Rare Disease Clinical Research Consortia and the Rare Disease Data and Technology Coordinating Center.
• Build a vasculitis clinical specimen bank for storage of serum,

Description from the Grant Application:
A consortium of investigators, institutions, and patient support groups will constitute a Rare Disease Clinical Research Consortium focused on a diverse group of disorders characterized by defects in steroidogenesis. We will study the longitudinal history of these rare disorders and determine the outcome of treatment on height, fertility, and gender. Long-standing informal collaboration between investigators at Mount Sinai School of Medicine, Rockefeller University, Columbia University, the University of Texas Southwestern Medical Center, the University of Québec, Hospital Debrosses (Lyons), and the Hospital das Clínicas da FMUSP (São Paulo) will facilitate the creation of a productive cooperative research network that draws on the extensive experience of each investigator. Clinical Research Centers at Mount Sinai, Rockefeller, and the University of Texas Southwestern Medical Center will participate. Each investigator in the consortium has followed a large group of patients with a specific genetic defect affe

Description from the Grant Application:
We seek to establish a research consortium that will facilitate clinical research in rare lung diseases by

1. Promoting collaboration among centers already focused on clinical research on rare lung diseases,
   
2. Attracting and training highly qualified investigators,
   
3. Collecting clinical data from geographically distributed patients into a large, centralized database, and
   
4. Making the accumulated clinical data available to those affected or possibly affected by a rare lung disease, their clinicians, clinical and basic investigators, and the general public.

Description from the Grant Application:
Rare disorders that are associated with an increased thrombotic risk include the antiphospholipid antibody syndromes (APS), heparin-induced thrombocytopenia (HIT), combined thrombophilic states, paroxysmal nocturnal hemoglobinuria, thrombotic thrombocytopenic purpura, and the catastrophic "thrombotic storm." These disorders frequently exhibit more "aggressive" clinical phenotypes, affecting arterial, venous, and/or microvascular beds. Diagnostic and/or therapeutic limitations exist for each of these disorders, and prospective studies are needed to more clearly define the syndromes and develop better therapies. This multi-institutional academic consortium focuses on rare thrombotic disorders and will

1) Establish a Rare Diseases Clinical Research Consortium focusing on rare thrombotic disorders. Investigators from four academic centers will bring together existing registries (e.g., the Antiphospholipid Syndrome Collaborative Registry) and programs [e.g., the Centers for Disease Control and Prevention (CDC)

Description from the Grant Application:
The project director will establish a Rare Diseases Clinical Research Center (RDCRC) at the University of North Carolina (UNC) and an associated consortium with three other geographically dispersed sites to study rare diseases of the airways. These four sites in the consortium will collaborate in diagnostic, genetic, and other studies in patients with genetic impairments in mucociliary clearance, specifically primary ciliary dyskinesia (PCD), variant forms of cystic fibrosis (CF), and pseudohypoaldosteronism (PHD). Patients with these unusual disorders with increased morbidity and mortality often have delayed (or incorrect) diagnoses because diagnostic tests are not readily available. The two central hypotheses are that

1. A broad-based systematic approach to the diagnostic evaluation of these patients will yield more precise diagnostic criteria and better diagnostic techniques, including genetic testing; and
   
2. Systematic evaluation of specific cohorts of these patients with state-of-the-
   

Description from the Grant Application:
The Principal and Co-Investigators propose the development of a coordinated and integrated rare liver diseases clinical research consortium. The consortium will include sites at the Children’s Hospital in Denver and five clinical sites within the United States, each with investigators who have extensive clinical experience, patient populations, and research programs for these disorders and each with a General Clinical Research Center (GCRC). The consortium will focus on investigations of five genetic causes of intrahepatic cholestasis. These disorders have serious if not fatal consequences (without liver transplantation) and severely affect the children’s normal growth and development. The five related disorders are a-1-antitrypsin deficiency, Alagille syndrome, progressive familial intrahepatic cholestasis (PFIC), bile acid synthesis and metabolism defects, and mitochondrial hepatopathies. The consortium will develop a longitudinal hypothesis-driven database study of these diseases. During this study, serum, DNA, and liver tissue will be obtained from all patients and stored for future studies. The consortium will also include

• three biological core facilities to ensure the highest quality analysis of genetic information, liver histopathology, and bile acid biochemistry for subjects enrolled in this study;
• an administrative core;
• a pilot/demonstration project program to encourage innovative scientific investigation;
• a training program in order to attract new investigators to the study of rare liver diseases; and
• development of electronic Internet-based clinical, educational, histologic, and research resources for these diseases.

Description from the Grant Application:
This proposal seeks support to establish a Data and Technology Coordinating Center (DTCC) for the Rare Diseases Clinical Research Network. The DTCC will play an active role in the development of the Network. It will facilitate research in the design of clinical protocols and the data management and analysis necessary to support them. Working with the Rare Diseases Clinical Research Consortia, the DTCC will make available a coordinated clinical data management system for the collection, storage, and analysis of data from multiple diseases and multiple clinical sites. The data management system will be a secure Web-based system that includes the capability to capture and integrate many different forms of data (clinical, imaging, genetics, pathology, etc.), and the scalability to serve as a national clinical information network. Among its features will be a user-friendly system for recruitment and referral, tools for cross-disease data mining, data sharing, and a public portal to relevant data resources. This application applies novel approaches and technologies for data management and training, includes the use of Web-based video streaming; and seeks to conduct research and development of new approaches to distributed computing, federated databases, and data mining.

For more information, please contact:

Rashmi Gopal-Srivastava, Ph.D.
Director, Extramural Research Program
Office of Rare Diseases, OD, NIH
6100 Executive Boulevard
Room 3B01-MSC 7518
Bethesda, MD 20892-7518
Telephone: 301 402-4336
Fax: 301 480-9655
E-mail: ord@od.nih.gov