Dose Escalation and Remission (DEAR) (DEAR)

• ClinicalTrials.gov Identifier: NCT00652145
• Recruitment Status: Completed
• First Posted: April 3, 2008
• Results First Posted: May 5, 2015
• Last Update Posted: May 5, 2015
• Sponsor: James Lewis
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Shire
• Information provided by (Responsible Party): James Lewis, University of Pennsylvania

Tracking Information

• First Submitted Date: April 1, 2008
• First Posted Date: April 3, 2008
• Results First Submitted Date: December 1, 2014
• Results First Posted Date: May 5, 2015
• Last Update Posted Date: May 5, 2015
• Study Start Date: September 2008
• Actual Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 4, 2015): Fecal Calprotectin Level <50µg/g [ Time Frame: 6 weeks after randomization ]
• Original Primary Outcome Measures (submitted: April 1, 2008): Concentration of fecal Calprotection [ Time Frame: 6 weeks after randomization ]

Current Secondary Outcome Measures (submitted: May 4, 2015)

• Fecal Calprotectin Level <100 µg/g [ Time Frame: at 6 weeks after randomization ]
• Fecal Calprotectin <200 µg/g [ Time Frame: at 6 weeks after randomization ]

• Original Secondary Outcome Measures (submitted: April 1, 2008): Clinical relapse of ulcerative colitis as measured by the Simple Clinical Colitis Activity Index (SCCAI) [ Time Frame: up to 48 weeks of followup ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Escalation and Remission (DEAR)
• Official Title: Test Treat Strategy to Prevent Ulcerative Colitis Relapse
• Brief 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.

Detailed Description

Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized controlled trial to investigate whether increasing doses of mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC.

We screened 119 patients with UC in remission on the basis of Simple Clinical Colitis Activity Index scores, FC >50 µg/g, and intake of no more than 3 g/day mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n = 26) or a group that increased its dose by 2.4 g/day for 6 weeks (n = 26). The primary outcome was continued remission with FC <50 µg/g. Secondary outcomes were continued remission with FC <100 µg/g or <200 µg/g (among patients with pre-randomization values above these levels).

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Ulcerative Colitis

Intervention

Drug: mesalamine

Increase dose by 2.4gm per day over baseline dose

Other Name: Lialda

Study Arms

• Experimental: Increase mesalamine dose by 2.4g/day
  Increase dose of mesalamine by 2.4 gm per day
  Intervention: Drug: mesalamine
• No Intervention: Maintain mesalmine dose
  Maintain current mesalamine dose at 2.4 g/day

• Publications *: Osterman MT, Aberra FN, Cross R, Liakos S, McCabe R, Shafran I, Wolf D, Hardi R, Nessel L, Brensinger C, Gilroy E, Lewis JD; DEAR Investigators. Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis. Clin Gastroenterol Hepatol. 2014 Nov;12(11):1887-93.e3. doi: 10.1016/j.cgh.2014.03.035. Epub 2014 Apr 30.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 4, 2015): 119
• Original Estimated Enrollment (submitted: April 1, 2008): 60
• Actual Study Completion Date: January 2013
• Actual Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00652145
• Other Study ID Numbers: K24DK078228( U.S. NIH Grant/Contract ); K24DK078228 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: James Lewis, University of Pennsylvania
• Study Sponsor: James Lewis

Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Shire

Investigators

• Principal Investigator: James D Lewis, MD, MSCE; University of Pennsylvania

• PRS Account: University of Pennsylvania
• Verification Date: May 2015