Clinical trial NCT03669822: Multi-center Acute Severe Ulcerative Colitis Cohort Study (MASCC)
Official title: Multi-center Acute Severe Ulcerative Colitis Cohort Study (MASCC)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ulcerative Colitis
Keywords: Ulcerative colitis
Inflammatory bowel disease
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
First posted: 2018-09-13
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hospitalized ulcerative colitis patients

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Inpatient response to medical management
timeFrame: In-hospital (approximately 1-2 weeks)
Secondary outcomes:
measure: Long-term response to medical management
timeFrame: 12 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Joanna Melia
state: Maryland
Study officials:
References: