Dose Escalation and Remission (DEAR)

NCT ID: NCT00652145

Last Updated: 2015-05-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2013-01-31

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).

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Increase mesalamine dose by 2.4g/day

Increase dose of mesalamine by 2.4 gm per day

Group Type: EXPERIMENTAL

mesalamine

Intervention Type: DRUG

Increase dose by 2.4gm per day over baseline dose

Maintain mesalmine dose

Maintain current mesalamine dose at 2.4 g/day

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

mesalamine

Increase dose by 2.4gm per day over baseline dose

Intervention Type: DRUG

Other Intervention Names

Lialda

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

Shire

INDUSTRY

Sponsor Role: collaborator

James Lewis

OTHER

Sponsor Role: lead

Responsible Party

James Lewis

Professor of Medicine and Epidemiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

James D Lewis, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Gastroenterology Group of Naples

Naples, Florida, United States

Shafran Gastroenterology Center

Winter Park, Florida, United States

Atlanta Gastroenterology Associates

Atlanta, Georgia, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Chevy Chase Clinical Research

Chevy Chase, Maryland, United States

Minnesota Gastroenterology, P.A.

Plymouth, Minnesota, United States

South Jersey Gastroenterology

Marlton, New Jersey, United States

University of Pennsylvania - Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24793028 (View on PubMed)

Other Identifiers

K24DK078228

Identifier Type: NIH

Identifier Source: secondary_id

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K24DK078228

Identifier Type: NIH

Identifier Source: org_study_id

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