Dose Escalation and Remission (DEAR)
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: mesalamine
Intervention description: Increase dose by 2.4gm per day over baseline dose
Intervention MeSH terms: Mesalamine
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 119.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ulcerative colitis; inflammatory bowel disease

Summary:

      The proposed study will test whether increasing Lialda dose can reduce fecal calprotectin
      (FCP) levels, a marker of intestinal inflammation that is highly predictive of the risk of
      relapse among patients with quiescent ulcerative colitis. Sixty patients with FCP levels
      <50µg/g stool will be observed for 48 weeks. All patients will have FCP concentration
      measured using a commercially available assay at enrollment, 6 weeks and 12 weeks. All
      patients with persistently elevated FCP will receive one or both of the following
      interventions: change in the mesalamine formulation to Lialda and/or increase in the dose of
      Lialda. Reduction in FCP levels below 50µg/g stool 6 weeks after randomization will be the
      primary outcome. The proportion of patients achieving this outcome will be compared between
      groups using Fisher's exact test. All randomized patients as well as those who were excluded
      from the randomized trial because of a low FCP concentration at baseline will be followed to
      week 48 to determine the rate of clinical relapse.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Understand and sign the informed consent form.

          2. Have documented ulcerative colitis on the basis of usual diagnostic criteria including
             clinical symptoms and findings from endoscopy, radiology studies, and histology.

          3. Have a Simple Clinical Colitis Activity Index (SCCAI)55 score below 3 with no category
             value greater than 1 (Table 5).

          4. Three or fewer bowel movements per 24 hours at the time of enrollment.

          5. No visible blood in their bowel movements in the three days prior to enrollment.

          6. Have either been on a stable dose of mesalamine medication (oral, rectal or a
             combination of oral and rectal, including sulfasalazine) or on no mesalamine
             medications for at least 4 weeks prior to enrollment.

          7. Have been on either a stable dose of azathioprine, 6-mercaptopurine, or methotrexate
             or on none of these medications for at least 8 weeks prior to enrollment.

          8. Have experienced at least one flare of ulcerative colitis in the 2 years prior to
             enrollment. A flare is defined as an increase in stool frequency, bleeding, urgency
             and/or abdominal discomfort sufficient to warrant a change in medication dose or
             addition of a new medication.

          9. Most recently measured serum creatinine level in the preceding year less than 1.5
             mg/dL.

        Exclusion Criteria:

          1. Age less than 18

          2. Inability to speak and read English

          3. Presence of an ostomy or prior total or subtotal colectomy

          4. Current corticosteroid use or use within the two weeks prior to enrollment

          5. Remission for less than 4 weeks prior to enrollment

          6. Previous intolerance to mesalamine at doses greater than the current dose.

          7. Use of rectally administered mesalamine or steroids within the 2 weeks prior to
             enrollment.

          8. Currently taking more than 3.0 gm/day of mesalamine (oral or rectal). If on oral and
             rectal mesalamine, the combined dose is more than 3.0 gm/day.

          9. Use of anti-TNFα therapies within the 8 weeks prior to enrollment and/or intent to use
             anti-TNFα therapies as maintenance therapy in the coming 12 weeks.

         10. Pregnant or breast feeding women.

         11. Use of an experimental therapy for ulcerative colitis in the 8 weeks prior to
             enrollment.

         12. Any condition that the investigator feels will make completion of the study unlikely.

         13. Use of cyclosporine in the two weeks prior to enrollment.

         14. Moderate or severe abdominal tenderness on examination at time of enrollment.