Dose Escalation and Remission (DEAR)

NCT00652145 | Completed Phase 4 Results

• 1 other identifier: K24DK078228
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 8

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.

Conditions

Ulcerative Colitis

Keywords

ulcerative colitis; inflammatory bowel disease

Outcome Measures

Primary Outcomes (1)

• Fecal Calprotectin Level <50µg/g

  6 weeks after randomization

Secondary Outcomes (2)

• Fecal Calprotectin Level <100 µg/g

  at 6 weeks after randomization

• Fecal Calprotectin <200 µg/g

  at 6 weeks after randomization

Study Arms (2)

Increase mesalamine dose by 2.4g/day

EXPERIMENTAL

Increase dose of mesalamine by 2.4 gm per day

Drug: mesalamine

Maintain mesalmine dose

NO INTERVENTION

Maintain current mesalamine dose at 2.4 g/day

Interventions

mesalamine DRUG

Increase dose by 2.4gm per day over baseline dose

Also known as: Lialda

Increase mesalamine dose by 2.4g/day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and sign the informed consent form.
• Have documented ulcerative colitis on the basis of usual diagnostic criteria including clinical symptoms and findings from endoscopy, radiology studies, and histology.
• Have a Simple Clinical Colitis Activity Index (SCCAI)55 score below 3 with no category value greater than 1 (Table 5).
• Three or fewer bowel movements per 24 hours at the time of enrollment.
• No visible blood in their bowel movements in the three days prior to enrollment.
• 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.
• 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.
• 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.
• Most recently measured serum creatinine level in the preceding year less than 1.5 mg/dL.

You may not qualify if:

• Age less than 18
• Inability to speak and read English
• Presence of an ostomy or prior total or subtotal colectomy
• Current corticosteroid use or use within the two weeks prior to enrollment
• Remission for less than 4 weeks prior to enrollment
• Previous intolerance to mesalamine at doses greater than the current dose.
• Use of rectally administered mesalamine or steroids within the 2 weeks prior to enrollment.
• 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.
• 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.
• Pregnant or breast feeding women.
• Use of an experimental therapy for ulcerative colitis in the 8 weeks prior to enrollment.
• Any condition that the investigator feels will make completion of the study unlikely.
• Use of cyclosporine in the two weeks prior to enrollment.
• Moderate or severe abdominal tenderness on examination at time of enrollment.

Sponsors & Collaborators

• James Lewis: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Shire: collaborator

Study Sites (8)

Gastroenterology Group of Naples

Naples, Florida, 34102, United States

Location

Shafran Gastroenterology Center

Winter Park, Florida, 32789, United States

Location

Atlanta Gastroenterology Associates

Atlanta, Georgia, 30342, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Chevy Chase Clinical Research

Chevy Chase, Maryland, 20815, United States

Location

Minnesota Gastroenterology, P.A.

Plymouth, Minnesota, 55446, United States

Location

South Jersey Gastroenterology

Marlton, New Jersey, 08053, United States

Location

University of Pennsylvania - Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 24793028 RESULT

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases

Interventions

Mesalamine

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Results Point of Contact

• Title: James D. Lewis, MD, MSCE
• Organization: University of Pennsylvania

lewisjd@mail.med.upenn.edu

215-573-5137

Study Officials

• James D Lewis, MD, MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine and Epidemiology

Study Record Dates

• First Submitted: April 1, 2008
• First Posted: April 3, 2008
• Study Start: September 1, 2008
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: May 5, 2015
• Results First Posted: May 5, 2015

Record last verified: 2015-05

Locations

US (8)