Mild to Moderate Ulcerative ColitisPhase 4MUPPITNCT01201122
Once Versus Twice Daily Mesalamine to Induce Remission in Pediatric Ulcerative Colitis
A Phase 4 study testing Mesalamine in people with Mild to Moderate Ulcerative Colitis, run by Wolfson Medical Center at 1 site in Israel.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Mild to Moderate Ulcerative Colitis
- What is being tested?
- Mesalamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 1 siteIsrael
- Study dates
- Sep 2010to Dec 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children 6-18 years of age, weight least 15kg.
- Diagnosis of UC, established by the presence of accepted clinical, radiologic, endoscopic and histologic criteria.
- Mild to moderate disease activity at the time of enrolment as judged by the Pediatric UC Activity Index (PUCAI) score 10-55 points.
- In general good health (other than the diagnosis of UC), based on medical history, physical examination, and screening laboratory results.
- Infectious colitis excluded by stool cultures, ova and parasite examination and Clostridium difficile assay.
- 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.
Who cannot join
- Weight <15 kg at enrolment
- Patients whose disease is confined to the rectum (i.e. proctitis).
- Fever >38.5 degrees.
- Patients with Crohn's colitis or with IBD type unclassified (IBD-U) according to Montreal classification.
- 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.
- Exacerbation associated with infectious organism in the stool.
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- Current treatment with steroids (any dose) or the need for steroid therapy as judged by the responsible gastroenterologist.
- 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.
- 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.
- Treatment with biologic therapy including, but not limited to: infliximab, certolizumab, adalimumab within 90 days prior to screening visit.
- 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.
- Known allergy to 5ASA, salicylates, or aminosalicylates.
- 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.
- 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).
- History of recurrent pancreatitis.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multi Center Ulcerative Colitis Pediatric Pentasa Intervention Trial (MUPPIT). A Randomized, Single-blinded, Controlled, Parallel, Induction Therapy With Once vs. Twice Daily Dosing of Pentasa in Pediatric UC.
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.
Read the detailed description
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
- Mild to Moderate Ulcerative Colitis
- Being tested
- Mesalamine
- Keywords
- Pediatric, Ulcerative colitis, 5-ASA, Mesalamine, Dosing
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MesalamineDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Weight based Mesalamine: Once daily | Experimental | Not described Receives: Drug: Mesalamine |
| Weight based Mesalamine: Twice daily | Experimental | Not described Receives: Drug: Mesalamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in mean PUCAI score between the groups.
Measured: At week 6 after initiation of therapy.
Secondary outcomes (1)
Treatment success defined as Complete response OR large partial response.
Complete response: A a PUCAI score <10 points AND a change of at least 10 points from baseline.
Small partial response: A a change in PUCAI score of at least 10 points from baseline AND a PUCAI score of ≥10 points.
Large partial response: A change in PUCAI score of at least 20 points from baseline AND a PUCAI score of ≥10 points.
Treatment Failure: A lack of improvement of at least 10 points from the baseline PUCAI score despite at least 3 weeks of treatment, or requirement of corticosteroids at any time.
Measured: At 3 and 6 weeks from initiation of therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild to Moderate Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wolfson Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Prof. Arie Levine, Wolfson Medical Center
- Investigators
- Arie Levine, MD, Study chair, Pediatric Gastroenterology and Nutrition Unit, The E. Wolfsom MC, Tel-Aviv Universiy, Holon, IsraelDan Turner, MD, PhD, Study director, Pediatric Gastroenterology and Nutrition Unit, The Hebrew Universitiy of Jerusalem, Shaare Zedek MC, Jerusalem, IsraelRon Shaoul, MD, Principal investigator, Pediatric Gastroenterology Unit, Meyer Children's Hospital, Rambam MC, Haifa, IsraelBatia Weiss, MD, Principal investigator, Safra Children's Hospital, Sheba MC, Tel-Hashomer, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01201122
- Sponsor's protocol ID
- 0052-10-WOMC
- Acronym
- MUPPIT
- Status last verified
- Dec 2015
- First submitted
- 12 Sep 2010
- Last updated
- 8 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi Center Ulcerative Colitis Pediatric Pentasa Intervention Trial (MUPPIT). A Randomized, Single-blinded, Controlled, Parallel, Induction Therapy With Once vs. Twice Daily Dosing of Pentasa in Pediatric UC.
- ClinicalTrials.gov ID
- NCT01201122
- Acronym / sponsor ID
- MUPPIT / 0052-10-WOMC
- Conditions
- Mild to Moderate Ulcerative Colitis
- Keywords
- Pediatric, Ulcerative colitis, 5-ASA, Mesalamine, Dosing
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Wolfson Medical CenterOther government
- Study start
- Sep 2010
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 14 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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!
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Weight based Mesalamine: Once daily | Experimental | Drug: Mesalamine |
| Weight based Mesalamine: Twice daily | Experimental | Drug: Mesalamine |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Children 6-18 years of age, weight least 15kg.
- Diagnosis of UC, established by the presence of accepted clinical, radiologic, endoscopic and histologic criteria.
- Mild to moderate disease activity at the time of enrolment as judged by the Pediatric UC Activity Index (PUCAI) score 10-55 points.
- In general good health (other than the diagnosis of UC), based on medical history, physical examination, and screening laboratory results.
- Infectious colitis excluded by stool cultures, ova and parasite examination and Clostridium difficile assay.
Key exclusion criteria (16 listed)
- Weight <15 kg at enrolment
- Patients whose disease is confined to the rectum (i.e. proctitis).
- Fever >38.5 degrees.
- Patients with Crohn's colitis or with IBD type unclassified (IBD-U) according to Montreal classification.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MesalamineDosing: 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). | Drug | Weight based Mesalamine: Once daily, Weight based Mesalamine: Twice daily |
Primary outcome
Difference in mean PUCAI score between the groups.
Time frame: At week 6 after initiation of therapy.
1 secondary outcome
Treatment success defined as Complete response OR large partial response.
Time frame: At 3 and 6 weeks from initiation of therapy.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arie Levine, MD study chair
Pediatric Gastroenterology and Nutrition Unit, The E. Wolfsom MC, Tel-Aviv Universiy, Holon, Israel
Dan Turner, MD, PhD study director
Pediatric Gastroenterology and Nutrition Unit, The Hebrew Universitiy of Jerusalem, Shaare Zedek MC, Jerusalem, Israel
Ron Shaoul, MD principal investigator
Pediatric Gastroenterology Unit, Meyer Children's Hospital, Rambam MC, Haifa, Israel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mesalamine in people with Mild to Moderate Ulcerative Colitis, run by Wolfson Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in mean PUCAI score between the groups. (time frame: At week 6 after initiation of therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2015.