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Dose Escalation and Remission (DEAR) (DEAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00652145
Recruitment Status : Completed
First Posted : April 3, 2008
Results First Posted : May 5, 2015
Last Update Posted : May 5, 2015
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
James Lewis, University of Pennsylvania

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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: mesalamine Phase 4

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 119 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Test Treat Strategy to Prevent Ulcerative Colitis Relapse
Study Start Date : September 2008
Actual Primary Completion Date : January 2013
Actual Study Completion Date : January 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Increase mesalamine dose by 2.4g/day
Increase dose of mesalamine by 2.4 gm per day
Drug: mesalamine
Increase dose by 2.4gm per day over baseline dose
Other Name: Lialda

No Intervention: Maintain mesalmine dose
Maintain current mesalamine dose at 2.4 g/day

Primary Outcome Measures :
  1. Fecal Calprotectin Level <50µg/g [ Time Frame: 6 weeks after randomization ]

Secondary Outcome Measures :
  1. Fecal Calprotectin Level <100 µg/g [ Time Frame: at 6 weeks after randomization ]
  2. Fecal Calprotectin <200 µg/g [ Time Frame: at 6 weeks after randomization ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00652145

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United States, Florida
Gastroenterology Group of Naples
Naples, Florida, United States, 34102
Shafran Gastroenterology Center
Winter Park, Florida, United States, 32789
United States, Georgia
Atlanta Gastroenterology Associates
Atlanta, Georgia, United States, 30342
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Chevy Chase Clinical Research
Chevy Chase, Maryland, United States, 20815
United States, Minnesota
Minnesota Gastroenterology, P.A.
Plymouth, Minnesota, United States, 55446
United States, New Jersey
South Jersey Gastroenterology
Marlton, New Jersey, United States, 08053
United States, Pennsylvania
University of Pennsylvania - Presbyterian Medical Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
James Lewis
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: James D Lewis, MD, MSCE University of Pennsylvania
Publications of Results:
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Responsible Party: James Lewis, Professor of Medicine and Epidemiology, University of Pennsylvania Identifier: NCT00652145    
Other Study ID Numbers: K24DK078228 ( U.S. NIH Grant/Contract )
K24DK078228 ( U.S. NIH Grant/Contract )
First Posted: April 3, 2008    Key Record Dates
Results First Posted: May 5, 2015
Last Update Posted: May 5, 2015
Last Verified: May 2015
Keywords provided by James Lewis, University of Pennsylvania:
ulcerative colitis
inflammatory bowel disease
Additional relevant MeSH terms:
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Colitis, Ulcerative
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents