Combination of Diet and 5ASA ( 5-aminosalicylic Acid) for Ulcerative Colitis (INDUCT)

Combination Therapy With Drug and Diet for Induction of Remission in Mild to Moderate Active Pediatric Ulcerative Colitis: A Single Blinded, International Randomized Controlled Trial

Combination Therapy with Drug and Diet for Induction of Remission in Mild to Moderate Active Pediatric Ulcerative colitis: A Single Blinded, International Randomized Controlled Trial

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Dietary supplement: Group 1- Control Diet; Dietary supplement: Group 2- UCD Diet

Detailed Description

This will be a 12 week, single blinded Randomized controlled trial (RCT) in children and adolescents with mild to moderate Ulcerative Collitis (UC) comparing 5ASA (recommended dosing 60-75 mg/kg/day; minimum 2.5 maximum 4 grams/day) with fiber restriction for 6 weeks followed by free diet (Group 1) to 5ASA with Ulcerative Collitis Diet (UCD) for 6 weeks, followed by the step down UCD for the next 6 weeks. Inclusion criteria will include children weighing >30kg, Pediatric Ulcerative Collitis Activity index (PUCAI) 10-45, no treatment with 5ASA (treatment naïve or treated with thiopurines for example) or currently treatment with 5ASA but <2 grams/day, ages 10-19 years, with disease extent E2-E4 by the Paris Classification. Patients on thiopurines may continue existing dose if dose is stable for at least 8 weeks.

Exclusion criteria are Patients with acute severe colitis (ASC) in the previous year, requiring oral or intravenous steroids in the previous 3 months, or patients treated with Anti- Tumor necrosis factor alfa (TNFa) regimens. Importantly, there is no placebo arm and both groups will be treated with the same currently recommended drug at currently recommended doses; the only difference between groups being their diets.

The primary endpoint will be remission defined as PUCAI<10 at week 6; Secondary endpoints will be response defined as a drop in PUCAI of 10 or remission at week 6, sustained steroid free remission week 12 and improvement in mucosal healing by Ulcerative Colitis Endoscopic Index of Severity (UCEIS) at week 12 as well as safety and tolerance. Intolerance will be defined as patients stopping the diet because of refusal to continue diet. Patients will be seen at weeks 0, 3, 6, and 12. PUCAI will be assessed at every visit; fecal calprotectin will be assessed at baseline, week 6 and 12. Sigmoidoscopy to assess mucosal healing will be performed at week 12 in patients who had a baseline colonoscopy or sigmoidoscopy. Sigmoidoscopies to evaluate healing will be voluntary and patients will not be excluded if they do not consent to have a follow up sigmoidoscopy.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Holon, Israel, 5822012
    • Wolfson MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent
2. Established diagnosis of UC by the Paris classification and Revised Porto Criteria.
3. Age: 10 - 19 years (inclusive)
4. Mild to moderate active disease, 10 ≤ PUCAI ≤45
5. Extent E2-E4 by the Paris classification
6. Weight >30 kg (ensures that patients who received 5ASA ≤2 grams are eligible)
7. Stable medication (IMM/ 5ASA) use or no change in medication use for the past 6 weeks. Patients who have received topical 5ASA therapy for <10 days and are active may be included if topical therapy is stopped at enrolment.
8. Patients not receiving 5ASA or using 5ASA<50mg/kg/day

Exclusion Criteria:

1. Any proven current infection such as positive stool culture, parasite or C. difficile.
2. Steroids (oral or intravenous) use in the past 3 months.
3. Patients who continue topical 5ASA or steroids after enrolment
4. Use of biologics in present or in past 6 months
5. Use of antibiotics for more than one week in the past 60 days
6. PUCAI >45
7. Acute severe UC in the previous 12 months.
8. Current extra intestinal manifestation of UC.
9. Primary Sclerosing Cholangitis (PSC) or Liver disease
10. Pregnancy.
11. Vegans or patients unwilling or unable to consume eggs
12. Inflammatory Bowel Disease (IBD) unclassified

Exclusion criteria Comments:

1. Stool culture, parasite or C. difficile will only be measured if the patient has diarrhea.
2. Patients who have received treatment enemas for 3 weeks or less then 3 days and are active, can be included but must stop the enemas on the day of enrolment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Control Diet 6 weeks of Oral 5ASA (standard recommended dosing 60-75 mg/kg/day; minimum 2.5, maximum 4 grams/day)+ Low residue diet and 6 more weeks of Oral 5ASA+ Free diet	Dietary supplement: Group 1- Control Diet; Oral 5ASA+ Low Residue Diet for 6 weeks and Oral 5ASA+ Free Diet for 6 more weeks
Experimental: Group 2; 6 weeks of Oral 5ASA (standard recommended dosing 60-75 mg/kg/day; minimum 2.5, maximum 4 grams/day)+ UC diet and 6 more weeks of Oral 5ASA+ UC diet stage 2	Dietary supplement: Group 2- UCD Diet; Oral 5ASA+ UC Diet for 6 weeks and Oral 5ASA+ UC Diet Stage 2 for 6 more weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PUCAI< 10 at week 6	Remission defined as PUCAI<10 at week 6	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A drop of PUCAI at least 10 points or remission	Response defined as a drop of PUCAI at least 10 points or remission (intention to treat) week 6 .	6 weeks
Mean/median change in Calprotectin at week 6	Mean/median change in Calprotectin at week 6	6 weeks
Sustained remission week 12	Sustained steroid & biologic free remission week 12	12 weeks
Need for topical therapy by week 12	Need for topical therapy by week 12	12 weeks
Change in UCEIS at week 12 ( optional)	Change in UCEIS at week 12 ( optional)	12 weeks
Tolerance to diet	Tolerance to diet defined by withdrawal from the study because of difficulties with the diet.	12 weeks

Collaborators and Investigators

• Sponsor: Prof. Arie Levine
• Investigators: Principal Investigator: Arie Levine, Prof, Wolfson Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Actual): May 30, 2022
• Study Completion (Actual): May 30, 2022

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 29, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 0001-19-WOMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No