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Once Versus Twice Daily Mesalamine to Induce Remission in Pediatric Ulcerative Colitis

NCT ID: NCT01201122

Last Updated: 2015-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-30

Study Completion Date

2015-12-31

Brief Summary

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The purpose of this study is to evaluate effectiveness of once daily dosing of Pentasa compared with twice daily in children with mild to moderate active ulcerative colitis.

Detailed Description

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Several randomized controlled trials (RCTs) have affirmed the efficacy of 5-aminosalicylic acid (5-ASA) and sulfasalazine in the acute treatment of mild to moderate exacerbations, as well as in the maintenance of clinical remission. Initially, common practice was to prescribe 5-ASA in three divided doses. Slow release once daily mesalamine with Multi Matrix System (MMX) technology was shown to be effective in induction and maintenance of remission of adult ulcerative colitis (UC). Since transit time of the colon is much slower than the small-bowel, and since the active ingredient should act locally on the colon, less frequent dosing of the regular formulation may also provide sufficient colonic coverage. Indeed, two recent studies among adults with UC suggest that once daily dosing of mesalamine (Pentasa® and Salofalk®) may be as or more effective than twice daily dosing.

To date, most RCTs have been conducted among adult patients and efficacy in children has been extrapolated from these data. However, childhood inflammatory bowel disease (IBD) may not be similar to adult onset disease. The prevalence of extensive colitis proximal to the splenic flexure is doubled in pediatric-onset UC compared to adults and extensive disease is consistently associated with more severe phenotype. On the other hand, studies in children with IBD often show better response to therapy than in adults. Therefore, American and European regulating agencies encourage pediatric studies be conducted for all approved drug products. It has been found that less than 50% of children with IBD are adherent with treatment, a figure associated with the understanding of the disease which is generally lower than in adults. Therefore, the advantage of once daily dosing of 5-ASA over twice-daily may be greater in children compares with adults.

The investigators hypothesize that once daily dosing of mesalamine is superior in effectiveness to twice daily dosing to induce remission in pediatric mild-moderate UC. We base this hypothesis on data previously found in adults and due to the expected higher adherence rate.

This study will compare two groups receiving an identical dose of the same non experimental medication, with the only difference being in the number of doses of the medication!

Conditions

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Mild to Moderate Ulcerative Colitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Weight based Mesalamine: Once daily

Group Type EXPERIMENTAL

Mesalamine

Intervention Type DRUG

Dosing: The current standard of care for pediatric UC is 75mg/kg/day of mesalamine (Pentasa) and should be in multiplications of 500mg (half sachets).

Patients will be randomized in blocks of six stratified by weight groups: 15- \<30 kg, 30-40kg, \>40kg.

For body wt. 15- \<20kg Arm: Once daily, 1000 mg (morning) and Placebo (0.5 sachet) (evening). Arm: Twice daily, 500mg (morning) and 500mg (evening).

For body wt: 20- \<30 kg Arm: Once daily, 1500mg (morning) and Placebo (0.5 sachet) (evening). Arm: Twice daily, 1000mg (morning) and 500mg (evening).

For Body wt. 30- \<40 kg Arm: Once daily, 2000mg (morning) and Placebo (1 sachet) (evening). Arm: Twice daily, 1000mg (morning) and 1000mg (evening).

For body wt. ≥40 kg Arm: Once daily, 3000mg (morning) and Placebo (1.5 sachet) (evening). Arm: Twice daily, 1500mg (morning) and 1500mg (evening).

Weight based Mesalamine: Twice daily

Group Type EXPERIMENTAL

Mesalamine

Intervention Type DRUG

Dosing: The current standard of care for pediatric UC is 75mg/kg/day of mesalamine (Pentasa) and should be in multiplications of 500mg (half sachets).

Patients will be randomized in blocks of six stratified by weight groups: 15- \<30 kg, 30-40kg, \>40kg.

For body wt. 15- \<20kg Arm: Once daily, 1000 mg (morning) and Placebo (0.5 sachet) (evening). Arm: Twice daily, 500mg (morning) and 500mg (evening).

For body wt: 20- \<30 kg Arm: Once daily, 1500mg (morning) and Placebo (0.5 sachet) (evening). Arm: Twice daily, 1000mg (morning) and 500mg (evening).

For Body wt. 30- \<40 kg Arm: Once daily, 2000mg (morning) and Placebo (1 sachet) (evening). Arm: Twice daily, 1000mg (morning) and 1000mg (evening).

For body wt. ≥40 kg Arm: Once daily, 3000mg (morning) and Placebo (1.5 sachet) (evening). Arm: Twice daily, 1500mg (morning) and 1500mg (evening).

Interventions

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Mesalamine

Dosing: The current standard of care for pediatric UC is 75mg/kg/day of mesalamine (Pentasa) and should be in multiplications of 500mg (half sachets).

Patients will be randomized in blocks of six stratified by weight groups: 15- \<30 kg, 30-40kg, \>40kg.

For body wt. 15- \<20kg Arm: Once daily, 1000 mg (morning) and Placebo (0.5 sachet) (evening). Arm: Twice daily, 500mg (morning) and 500mg (evening).

For body wt: 20- \<30 kg Arm: Once daily, 1500mg (morning) and Placebo (0.5 sachet) (evening). Arm: Twice daily, 1000mg (morning) and 500mg (evening).

For Body wt. 30- \<40 kg Arm: Once daily, 2000mg (morning) and Placebo (1 sachet) (evening). Arm: Twice daily, 1000mg (morning) and 1000mg (evening).

For body wt. ≥40 kg Arm: Once daily, 3000mg (morning) and Placebo (1.5 sachet) (evening). Arm: Twice daily, 1500mg (morning) and 1500mg (evening).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Children 6-18 years of age, weight least 15kg.
2. Diagnosis of UC, established by the presence of accepted clinical, radiologic, endoscopic and histologic criteria.
3. Mild to moderate disease activity at the time of enrolment as judged by the Pediatric UC Activity Index (PUCAI) score 10-55 points.
4. In general good health (other than the diagnosis of UC), based on medical history, physical examination, and screening laboratory results.
5. Infectious colitis excluded by stool cultures, ova and parasite examination and Clostridium difficile assay.
6. Ability and acceptance to participate in the study and follow study procedures, as evidenced by a parent/legal guardian signing a written informed consent and the child providing assent.

Exclusion Criteria

1. Weight \<15 kg at enrolment
2. Patients whose disease is confined to the rectum (i.e. proctitis).
3. Fever \>38.5 degrees.
4. Patients with Crohn's colitis or with IBD type unclassified (IBD-U) according to Montreal classification.
5. Treatment with oral 5-ASA oral preparation with at least 50mg/kg/day \> 3 days within 7 days prior to screening visit. Patients who are treated with 5-ASA \<50mg/kg/d may be enrolled as their dose will be increased significantly in this trial. A sensitivity analysis is planned including only 5-ASA naïve children.
6. Exacerbation associated with infectious organism in the stool.
7. Current treatment with steroids (any dose) or the need for steroid therapy as judged by the responsible gastroenterologist.
8. Rectal therapies (suppositories, foams, enemas etc) of all kind are allowed if the dose and frequency has remained stable during the previous 30 days prior to the screening visit. No changes are allowed after randomization and until completion of the study.
9. Treatment with immunomodulatory therapy including, but not limited to: 6 mercaptopurine (6-MP), azathioprine, cyclosporine, tacrolimus, rosiglitazone or methotrexate, is allowed if the dose and frequency has remained stable during the previous 90 days prior to the screening visit. No changes are allowed after randomization and until completion of the study.
10. Treatment with biologic therapy including, but not limited to: infliximab, certolizumab, adalimumab within 90 days prior to screening visit.
11. Pregnancy. All female patients of childbearing potential will undergo urine pregnancy testing at screening, must not be lactating, and willing to use acceptable contraception if sexually active.
12. Known allergy to 5ASA, salicylates, or aminosalicylates.
13. Existence of current renal disease, or a screening blood urea nitrogen (BUN) or creatinine value that is \> 1.5 times the upper limit of the age appropriate normal.
14. Existence of current hepatic disease, or liver tests (ALT, AST, T-Bili) that are \> 2 times the upper limit of normal, or the existence of Primary Sclerosing Cholangitis (PSC).
15. History of recurrent pancreatitis.
16. Any other laboratory or clinical condition that the investigator considers clinically significant that would impact the outcome of the study or the safety of the patient.
Minimum Eligible Age

6 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wolfson Medical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

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Prof. Arie Levine

Pediatric Gastroenterology and Nutrition Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Arie Levine, MD

Role: STUDY_CHAIR

Pediatric Gastroenterology and Nutrition Unit, The E. Wolfsom MC, Tel-Aviv Universiy, Holon, Israel

Dan Turner, MD, PhD

Role: STUDY_DIRECTOR

Pediatric Gastroenterology and Nutrition Unit, The Hebrew Universitiy of Jerusalem, Shaare Zedek MC, Jerusalem, Israel

Ron Shaoul, MD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Gastroenterology Unit, Meyer Children's Hospital, Rambam MC, Haifa, Israel

Batia Weiss, MD

Role: PRINCIPAL_INVESTIGATOR

Safra Children's Hospital, Sheba MC, Tel-Hashomer, Israel

Locations

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Wolfson Medical Center

Holon, , Israel

Site Status

Countries

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Israel

Other Identifiers

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0052-10-WOMC

Identifier Type: -

Identifier Source: org_study_id