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

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
Condition	Ulcerative Colitis
Intervention	Drug: mesalamine
Enrollment	119

Participant Flow

Recruitment Details	We screened 150 patients and enrolled 119 patients with UC in remission on the basis of SCCAI score. 58 patients had baseline fecal calprotectin(FC) <50 µg/g. These patients were followed in an observational arm. 61 had FC >= 50 µg/g,whose current mesalamine dose <3g/day. See preassignment details.
Pre-assignment Details	Among 61 pts with FC >=50 µg/g at week 0, 26 were taking non-MMX mesalamine at baseline and switched to MMX mesalamine 2.4g/day. Of these, by week 6, 2 had a repeat FC <50 µg/g, 3 had a flare of UC and 4 were noncompliant with study protocol or no longer interested in participating. The remaining 52 patients were included in the randomized trial.


Arm/Group Title	Increase Dose of Mesalamine	Maintain Baseline Mesalamine Dose
Arm/Group Description	Increase dose of mesalamine by 2.4g...	Maintain baseline mesalamine dose f...
Arm/Group Description	Increase dose of mesalamine by 2.4gm per day over baseline dose for six weeks	Maintain baseline mesalamine dose for six weeks
Period Title: Overall Study
Started	26	26
Completed	26	26
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Increase Mesalamine Dose	Maintain Mesalamine Dose	Total
Arm/Group Description		Participants were randomized to inc...	Participants were randomized to mai...	Total of all reporting groups
Arm/Group Description		Participants were randomized to increase dose of mesalamine by 2.4 gm per day over their baseline dose	Participants were randomized to maintain their baseline mesalamine dose	Total of all reporting groups
Overall Number of Baseline Participants		26	26	52
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Inter-Quartile Range) Unit of measure: Years
	Number Analyzed	26 participants	26 participants	52 participants
		43.8 (30.5 to 57.1)	48.8 (33.5 to 60.4)	46.5 (32.0 to 58.0)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	26 participants	26 participants	52 participants
	Female	11 42.3%	13 50.0%	24 46.2%
	Male	15 57.7%	13 50.0%	28 53.8%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	26 participants	26 participants	52 participants
	American Indian or Alaska Native	1 3.8%	0 0.0%	1 1.9%
	Asian	1 3.8%	0 0.0%	1 1.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 7.7%	4 15.4%	6 11.5%
	White	22 84.6%	21 80.8%	43 82.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	1 3.8%	1 1.9%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	26 participants	26 participants	52 participants
United States		26	26	52
Tobacco use Measure Type: Number Unit of measure: Participants	Number Analyzed	26 participants	26 participants	52 participants
Current		0	2	2
Prior		6	8	14
Never		20	16	36
Extent of disease Measure Type: Number Unit of measure: Participants	Number Analyzed	26 participants	26 participants	52 participants
Proctitis		8	2	10
Left-sided		9	12	21
Extensive		9	11	20
Other		0	1	1
Median duration of UC Median (Inter-Quartile Range) Unit of measure: Years
	Number Analyzed	26 participants	26 participants	52 participants
		11.9 (3.7 to 19.8)	6.5 (2.2 to 11.9)	8.9 (2.8 to 15.9)
Median of duration of remission at baseline Median (Inter-Quartile Range) Unit of measure: Years
	Number Analyzed	26 participants	26 participants	52 participants
		0.3 (0.2 to 1.0)	0.5 (0.2 to 1.1)	0.4 (0.2 to 1.0)
Median fecal calprotectin immediately before randomization Median (Inter-Quartile Range) Unit of measure: µg/g
	Number Analyzed	26 participants	26 participants	52 participants
		174 (67.0 to 439)	214 (80.0 to 439)	195 (69 to 461)
Currrent oral mesalamine Measure Type: Number Unit of measure: Participants	Number Analyzed	26 participants	26 participants	52 participants
Non-MMX formulation		8	9	17
MMX formulation		14	12	26
None		4	5	9
Current rectal mesalamine Measure Type: Number Unit of measure: Participants	Number Analyzed	26 participants	26 participants	52 participants
Yes		2	2	4
No		24	24	48
Current thiopurine Measure Type: Number Unit of measure: Participants	Number Analyzed	26 participants	26 participants	52 participants
Yes		6	4	10
No		20	22	42
Prior corticosteroids Measure Type: Number Unit of measure: Participants	Number Analyzed	26 participants	26 participants	52 participants
Yes		11	17	28
No		15	9	24
Prior rectal corticosteroids Measure Type: Number Unit of measure: Participants	Number Analyzed	26 participants	26 participants	52 participants
Yes		6	7	13
No		20	19	39
Prior cyclosporine Measure Type: Number Unit of measure: Participants	Number Analyzed	26 participants	26 participants	52 participants
Yes		0	1	1
No		26	25	51
Prior anti-tumor necrosis factor agent Measure Type: Number Unit of measure: Participants	Number Analyzed	26 participants	26 participants	52 participants
Yes		2	0	2
No		24	26	50

Outcome Measures

1.Primary Outcome


Title	Fecal Calprotectin Level <50µg/g
Description	[Not Specified]
Description	[Not Specified]
Time Frame	6 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Increase Mesalamine Dose by 2.4g/Day	Maintain Mesalmine Dose
Arm/Group Description:	Increase dose of mesalamine by 2.4 ...	Maintain current mesalamine dose at...
Arm/Group Description:	Increase dose of mesalamine by 2.4 gm per day mesalamine: Increase dose by 2.4gm per day over baseline dose	Maintain current mesalamine dose at 2.4 g/day
Overall Number of Participants Analyzed	26	26
Measure Type: Number Unit of Measure: participants
	7	1

2.Secondary Outcome


Title	Fecal Calprotectin Level <100 µg/g
Description	[Not Specified]
Description	[Not Specified]
Time Frame	at 6 weeks after randomization

Outcome Measure Data

Analysis Population Description

38 participants with baseline FC>=100ug/g


Arm/Group Title	Increase Dose of Mesalamine	Maintain Baseline Mesalamine Dose
Arm/Group Description:	Increase dose of mesalamine by 2.4g...	Maintain baseline mesalamine dose f...
Arm/Group Description:	Increase dose of mesalamine by 2.4gm per day over baseline dose for six weeks	Maintain baseline mesalamine dose for six weeks
Overall Number of Participants Analyzed	19	19
Measure Type: Number Unit of Measure: participants
	10	3

3.Secondary Outcome


Title	Fecal Calprotectin <200 µg/g
Description	[Not Specified]
Description	[Not Specified]
Time Frame	at 6 weeks after randomization

Outcome Measure Data

Analysis Population Description

25 participants with baseline FC>=200ug/g


Arm/Group Title	Increase Dose of Mesalamine	Maintain Baseline Mesalamine Dose
Arm/Group Description:	Increase dose of mesalamine by 2.4g...	Maintain baseline mesalamine dose f...
Arm/Group Description:	Increase dose of mesalamine by 2.4gm per day over baseline dose for six weeks	Maintain baseline mesalamine dose for six weeks
Overall Number of Participants Analyzed	13	12
Measure Type: Number Unit of Measure: participants
	10	2

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Participants were asked at each visit if they experienced any new symptoms or whether they were diagnosed with any new medical conditions since their last visit. At each visit, participants were also asked if they had any of the following conditions over the prior 3 days: Erythema nodosum Pyoderma gangrenosum Uveitis IBD-associated arthritis

Arm/Group Title	Increase Dose of Mesalamine		Maintain Baseline Mesalamine Dose
Arm/Group Description	Increase dose of mesalamine by 2.4g...		Maintain baseline mesalamine dose f...
Arm/Group Description	Increase dose of mesalamine by 2.4gm per day over baseline dose for six weeks		Maintain baseline mesalamine dose for six weeks
All-Cause Mortality
	Increase Dose of Mesalamine		Maintain Baseline Mesalamine Dose
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Increase Dose of Mesalamine		Maintain Baseline Mesalamine Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0.00%)		0/26 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Increase Dose of Mesalamine		Maintain Baseline Mesalamine Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/26 (42.31%)		7/26 (26.92%)
Blood and lymphatic system disorders
iron deficiency anemia ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
Cardiac disorders
Palpitations ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
Eye disorders
itchy eyes ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
Dry eyes ^†	0/26 (0.00%)	0	1/26 (3.85%)	1
Gastrointestinal disorders
Abdominal pain ^†	0/26 (0.00%)	0	1/26 (3.85%)	1
blood in stool ^†	1/26 (3.85%)	1	2/26 (7.69%)	2
Constipation ^†	0/26 (0.00%)	0	1/26 (3.85%)	1
diarrhea ^†	3/26 (11.54%)	3	1/26 (3.85%)	1
Bloating ^†	2/26 (7.69%)	2	0/26 (0.00%)	0
Flatulence ^†	1/26 (3.85%)	1	1/26 (3.85%)	1
Worsening Colitis ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
increase mucous ^†	0/26 (0.00%)	0	1/26 (3.85%)	1
General disorders
dizziness ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
Fatigue ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
headache ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
Vitamin B12 deficiency ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
Lower back pain ^†	0/26 (0.00%)	0	1/26 (3.85%)	1
Infections and infestations
Fever ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
Fungal infection ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
Upper respiratory infection ^†	1/26 (3.85%)	1	1/26 (3.85%)	1
Urinary tract infection ^†	1/26 (3.85%)	1	0/26 (0.00%)	0
Skin and subcutaneous tissue disorders
acne ^†	0/26 (0.00%)	0	1/26 (3.85%)	1
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	James D. Lewis, MD, MSCE
Organization:	University of Pennsylvania
Phone:	215-573-5137
EMail:	lewisjd@mail.med.upenn.edu

Publications of Results:

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.

Layout table for additonal information

Responsible Party:	James Lewis, University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00652145
Other Study ID Numbers:	K24DK078228 ( U.S. NIH Grant/Contract ) K24DK078228 ( U.S. NIH Grant/Contract )
First Submitted:	April 1, 2008
First Posted:	April 3, 2008
Results First Submitted:	December 1, 2014
Results First Posted:	May 5, 2015
Last Update Posted:	May 5, 2015

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