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Dose Escalation and Remission (DEAR) (DEAR)

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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:
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  ICMJE April 1, 2008
First Posted Date  ICMJE April 3, 2008
Results First Submitted Date  ICMJE December 1, 2014
Results First Posted Date  ICMJE May 5, 2015
Last Update Posted Date May 5, 2015
Study Start Date  ICMJE September 2008
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2015)
Fecal Calprotectin Level <50µg/g [ Time Frame: 6 weeks after randomization ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 1, 2008)
Concentration of fecal Calprotection [ Time Frame: 6 weeks after randomization ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Dose Escalation and Remission (DEAR)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE Drug: mesalamine
Increase dose by 2.4gm per day over baseline dose
Other Name: Lialda
Study Arms  ICMJE
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 4, 2015)
119
Original Estimated Enrollment  ICMJE
 (submitted: April 1, 2008)
60
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00652145
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party James Lewis, University of Pennsylvania
Study Sponsor  ICMJE James Lewis
Collaborators  ICMJE
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Shire
Investigators  ICMJE
Principal Investigator: James D Lewis, MD, MSCE University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP