Multi-center Acute Severe Ulcerative Colitis Cohort Study (MASCC) (MASCC)

Ulcerative colitis (UC) is a chronic, progressive immunologically mediated disease affecting nearly 1 million Americans. Up to one third of patients with UC will require hospitalization for severe disease (termed 'acute severe colitis (ASUC)'), often within the first year after diagnosis. Investigators will develop a large multi-center cohort of patients with ASUC with homogeneously collected detailed longitudinal clinical and laboratory data.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Other: Standard of care

Detailed Description

Ulcerative colitis (UC) is a chronic, progressive immunologically mediated disease affecting nearly 1 million Americans. Up to one third of patients with UC will require hospitalization for severe disease (termed 'acute severe colitis (ASUC)'), often within the first year after diagnosis. Advances in therapy for UC with the availability of effective biologics have revolutionized the medical care of UC, improving ability to achieve remission and reducing the need for colectomy for refractory disease. However, despite this general progress, investigators have not witnessed a corresponding temporal improvement in disease outcomes among those with the most severe disease. As well, providers lack the ability to 'personalize' care for UC by predicting up front which patients may develop ASUC or fail medical therapy and may benefit from early surgery, preventing protracted morbidity.

Over one-third of patients with ASUC will be refractory to intravenous steroids, the cornerstone for initial management of this condition. Infliximab and cyclosporine, the two most commonly used medical rescue therapies for this cohort, have comparable short- and long-term efficacy in two randomized controlled trials. However, up to a third of patients will not respond to such medical rescue. Lack of response is poorly understood and may be multifactorial with both patient- and drug-related factors. Among the latter, those with severe disease may have greater fecal loss of infliximab resulting in lack of efficacy. Attempts to overcome this have included accelerated induction with infliximab administered up front at a higher dose (10mg/kg) or more frequent intervals. A small single center retrospective study of only 50 patients among whom 15 received accelerated induction showed reduced short-term but not long-term rates of colectomy with this approach. However, a robust and generalizable comparison of the two infliximab induction treatment strategies are lacking. A key factor limiting study of ASUC is the lack of availability of large cohorts with detailed clinical information and linked specimens.

Here, investigators will develop a large multi-center cohort of patients with ASUC with homogeneously collected detailed longitudinal clinical and laboratory data. To the investigators' knowledge, this will be the first of its kind in the United States, and will be a key resource to understand the natural history, risk stratify and optimize therapeutic algorithms for care of patients with ASUC. A sub-study with blood, stool and biopsy specimens can be utilized for translational research into mechanisms of lack of response and development of biomarkers. The infrastructure of this network will also serve as a valuable resource for clinical trials of new therapies and novel strategies, a significant unmet need.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Joanna MP Melia, MD; Phone Number: 4109554916; Email: jpeloqu2@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Joanna Melia
      • Contact: Joanna MP Melia, MD; Email: jpeloqu2@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Hospitalized ulcerative colitis patients

Description

Inclusion Criteria:

• Patients 18-80 years
• UC or IBD-unspecified (IBDU) diagnosed according to standard criteria
• Active disease defined as Simple Clinical Colitis Activity Index > 2 (day/night bowel frequency, urgency with defecation, blood in stool, general well-being, and extracolonic features)
• Admitted to the hospital
• Initiating intravenous corticosteroid therapy or medical rescue therapy

Exclusion Criteria:

• Patients with quiescent disease
• Inability to provide informed consent
• Prior colitis related surgery including J-pouch or stoma
• Non-IBD related hospital admission
• Women who are pregnant (from the specimen substudy only)
• Non - English speaking

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Inpatient ulcerative colitis patients; Patients hospitalized for acute severe ulcerative colitis will be invited to enroll. Participants will be treated at the discretion of their treating physicians per standard of care. We expect some participants will be treated with standard versus accelerated infliximab dosing, permitting comparison, in addition to other treatment strategies.	Other: Standard of care; Care decisions driven by local physicians; this is an observational cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inpatient response to medical management	Response assessed by the following clinical care decisions based on binary outcomes: need for more than 1 dose of infliximab (yes=1 or no=0), switch in medical therapies (yes=1 or no=0), and need for surgery (yes=1 or no=0)	In-hospital (approximately 1-2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term response to medical management	Response assessed by the following clinical care decisions based on binary outcomes: need for accelerated dosing of infliximab as defined by high-dose (10mg/kg) or more than 3 doses over the first 6 weeks of therapy (yes=1 or no=0), switch in medical therapies (yes=1 or no=0), and need for surgery (yes=1 or no=0)	12 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Massachusetts General Hospital
• Investigators: Principal Investigator: Joanna MP Melia, MD, Johns Hopkins University; Principal Investigator: Ashwin Ananthakrishnan, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: May 29, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (Actual): September 13, 2018

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Ulcerative colitis; Inflammatory bowel disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: IRB00174643

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No