Dose Escalation and Remission (DEAR)

• Status: Completed
• Trial end date: 2013-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: James Lewis
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Shire
• Treatments: Mesalamine

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.