CCFA Clinical Research Alliance

Collaborating to address critical questions in IBD management and treatment.

Introduction

CCFA’s Clinical Research Alliance (CRA) is a network of clinical research centers throughout the country that are participating in a variety of studies to address critical IBD management and treatment questions. Current CRA studies focus on specific IBD treatment regimens and their impact on disease progression and severity. Discoveries promise to advance our understanding of the best strategies that lead to positive health outcomes and improved quality of life for patients of all ages.

Background

Established in 1996, the CRA’s mission is “to ask and answer clinically relevant questions in IBD that would not otherwise be studied.” Today, it is comprised of a collaborative network of 69 clinical research centers around the country, the highest number of sites since the network’s inception. In addition to helping ensure that key IBD studies are performed efficiently and with the largest possible samples of patients, the CRA encourages clinical researchers to enter the field of IBD.

All CRA research is pre-approved by its Steering and Oversight Committees, and any member of the network can participate. CRA chairs serve on the steering committees of each trial and regularly follow-up with principal investigators. Progress reports for all studies are shared in a bi-annual newsletter. For more information regarding the CRA, or to become a member please visit www.ccfacra.org

Current Leadership

Hans Herfarth, MD, PhD
Chair, Clinical Research Alliance
University of North Carolina at Chapel Hill

Peter Higgins, MD, PhD, MPH
Co-Chair, Clinical Research Alliance
University of Michigan Medical School

S. Alandra Weaver, MPH
Director, Clinical Research Alliance
Crohn’s & Colitis Foundation of America

Robert S. Sandler, MD, MPH
Chair, Data Management Center
University of North Carolina at Chapel Hill

Current Activities and Objectives

Current CRA studies include:

MARQUEE: Does Mucosal Healing Matter for Clinically Quiescent Ulcerative Colitis?

There is increasing evidence that patients with ulcerative colitis (UC) have better long-term outcomes, including lower rates of disease flares, hospitalization and surgery, if their gut mucosa is healed. MARQUEE examines whether treating with medication to the point of mucosal healing, irrespective of clinical symptoms, is an effective or warranted strategy. Current investigation is setting the stage for a large randomized trial in which patients with clinically inactive UC will either remain on 5-ASA medications or step-up to immunosuppressives to test whether treating to the point of mucosal healing leads to improved clinical outcomes in the long run. 

MERIT-UC: MEthotrexate Response In Treatment of Ulcerative Colitis

MERIT-UC is a randomized, double blind, prospective trial that investigates the efficacy of Methotrexate (MTX) in induction and maintenance of steroid free remission in ulcerative colitis (UC). Several retrospective and prospective case series demonstrate the clinical efficacy of MTX in patients with UC. This study is a prospective placebo controlled study to investigate the safety and efficacy of 25 mg MTX applied subcutaneously once weekly in patients with active UC, who are either steroid dependent or are intolerant or not responding to mesalamine or azathioprine/6-mercaptopurine therapy or have no response/lost response to infliximab prior to study inclusion. Discoveries will help meet the persistent, unmet need for additional effective and affordable therapies for patients with UC.

PIANO: Pregnancy in Inflammatory Bowel Disease And Neonatal Outcomes

Women with IBD exposed to azathioprine/6-mp and anti-TNF therapies during pregnancy and conception have different pregnancy outcomes than women with IBD not exposed to these medications. PIANO will determine whether the rates of congenital malformations, spontaneous abortion, preterm birth and small for gestational age (SGA) infants in a prospective national sample of women with IBD exposed to these medications are greater than among unexposed IBD-affected women. The study will also determine four-year outcomes of infants born to mothers with IBD with respect to developmental delay, infections and other health related complications.

PUCCINI: Prospective Cohort of Ulcerative Colitis and Crohn’s Disease Patients Undergoing Surgery to Identify Risk Factors for Post-Operative INfection I

IBD patients exposed to anti-TNF therapies pre-operatively have a higher rate of post-operative infections within 90 days than patients not exposed to these medications. PUCCINI will determine whether the rate of post-operative infection (surgical site infections and extra-abdominal infections) in a prospective multi-center sample of IBD patients undergoing abdominal surgery is greater in patients exposed to anti-TNF therapy than those unexposed to these medications. The study will determine whether anti-TNF exposure is an independent risk factor for post-operative infection in IBD patients undergoing abdominal surgery.

APRIL: Autoimmune Paradoxical Reactions in IBD Longitudinal cohort

The use of biologics, in particular anti-tumor necrosis factor-alpha (anti-TNF) agents, for the treatment of IBD has increased dramatically in the US over the past 20 years, with demonstrated safety and efficacy. However, reports of difficult-to-manage autoimmune reactions such as psoriaform skin lesions, vasculitis, demyelinating disorders or drug-induced lupus are increasing, and may result in discontinuation of an otherwise effective agent. APRIL is a prospective, multi-center, longitudinal cohort of IBD patients newly initiated on biologic therapies that will help determine: the incidence and time to development of paradoxical immune reaction; the risk factors (i.e., serum markers such as ANA, drug levels, phenotypic, genetic or demographic data) for development of paradoxical immune reaction; whether risks of paradoxical immune reaction differ by anti-TNF formulation; and whether subsequent relapse occurs with alternate formulation.

SAPPHIRE: Safety of Immunosuppression in A Prospective Cohort of Inflammatory Bowel Disease Patients with a History of Cancer

The paradigm of “treat to target” in IBD has resulted in early adoption of immunosuppressive therapies (thiopurines, methotrexate, anti-TNF agents, anti-integrin agents) to achieve clinical and endoscopic remission. However, an important concern to both patients and physicians who are considering these IBD treatments is the potential associated cancer risk. SAPPHIRE studies the effect of immunosuppressive therapy for IBD on incident (new or recurrent) cancers in IBD patients with a previous history of cancer. A prospective Registry of such patients is being developed to follow them for new or recurrent cancer.

Standardized Clinical Data Recording Tool

A new data-collection tool, the “IBD Smartform,” has been developed for use in the routine care of patients to capture their clinical phenotype, prior surgeries, prior medical therapies, current symptoms, key exam findings, and endoscopic and diagnostic test performance. It is designed to also allow patients to directly enter information related to current symptoms and outcome measures identified as important quality of care metrics for IBD, and to compute common disease activity indices. In this pilot project, investigators will: examine the process of implementing the IBD Smartform into practice and develop implementation strategies; and determine whether the tool facilitates collection of research quality data and impact on physicians’ satisfaction.

When fully implemented, the IBD Smartform promises to improve patient care and enable creation of the world’s largest cohort of patients with IBD with granular and uniform clinical information available for research.