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

• ClinicalTrials.gov Identifier: NCT03980405
• Recruitment Status: Terminated
• First Posted: June 10, 2019
• Last Update Posted: June 1, 2022
• Sponsor: Prof. Arie Levine
• Information provided by (Responsible Party): Prof. Arie Levine, Wolfson Medical Center

Tracking Information

• First Submitted Date: June 5, 2019
• First Posted Date: June 10, 2019
• Last Update Posted Date: June 1, 2022
• Actual Study Start Date: April 1, 2020
• Actual Primary Completion Date: May 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 5, 2019)

PUCAI< 10 at week 6 [ Time Frame: 6 weeks ]

Remission defined as PUCAI<10 at week 6

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 5, 2019)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Combination of Diet and 5ASA ( 5-aminosalicylic Acid) for Ulcerative Colitis
• Official Title: 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
• Brief Summary: 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

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
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Masking Description:

Physicians will be blinded to the randomization and dietary advice received

Primary Purpose: Treatment

• Condition: Ulcerative Colitis

Intervention

• Dietary Supplement: Group 1- Control Diet
  Oral 5ASA+ Low Residue Diet for 6 weeks and Oral 5ASA+ Free Diet for 6 more weeks
• Dietary Supplement: Group 2- UCD Diet
  Oral 5ASA+ UC Diet for 6 weeks and Oral 5ASA+ UC Diet Stage 2 for 6 more weeks

Study Arms

• 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
  Intervention: Dietary Supplement: Group 1- Control Diet
• 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
  Intervention: Dietary Supplement: Group 2- UCD Diet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 29, 2022): 12
• Original Estimated Enrollment (submitted: June 5, 2019): 62
• Actual Study Completion Date: May 30, 2022
• Actual Primary Completion Date: May 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 19 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT03980405
• Other Study ID Numbers: 0001-19-WOMC
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Prof. Arie Levine, Wolfson Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Prof. Arie Levine
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Arie Levine, Prof; Wolfson Medical Center

• PRS Account: Wolfson Medical Center
• Verification Date: May 2022