Use of a Novel Diet (UC DIET) for Treatment of Mild to Moderate Active Pediatric Ulcerative Colitis

Phase 4

Completed

• Conditions: Ulcerative Colitis (UC)
• Interventions: Other: Ulcerative Colitis Diet; Drug: Antibiotic cocktail

• Registration Number: NCT02345733
• Lead Sponsor: Prof. Arie Levine

Brief Summary

The goal of the study is to evaluate strategies that target the microbiota for the treatment of Ulcerative Colitis , This study will involve a novel diet that the investigators developed , based on the hypothesis that UC involves dysbiosis , underutilzation of certain metabolic pathways and use of pathways that increase risk of inflammation . The investigators have postulated that manipulation of colonic bacterial metabolism with this diet will induce remission in UC without involving additional immune suppression.

Detailed Description

Ulcerative colitis is a chronic inflammatory disease primarily involving the colon. It has long been considered to be due to a dysregulated immune response targeting the colon, and involves unknown environmental factors . Recent studies have highlighted several characteristics which may suggest that UC is associated with alterations of the microbiota, defective production of short chain fatty acids and an impaired mucous layer. However at present, no effective therapy targets the microbiota or its interaction with the colonic epithelium. UC in humans is characterized by increased mucosal sulfides and increased sulfate and sulfide reducing bacteria and activation of amino acid metabolism pathways which impair butyrate production, whereas certain dietary patterns in humans and rodent models may induce dysbiosis and favor sulphide reducing bacteria. Further support for targeting the microbiota includes several studies demonstrating that antibiotics might be helpful for severe refractory colitis. Development of treatment strategies that target the microbiota could reduce exposure to immune suppression, and add new therapeutic strategies that do not exist at present.

Though diet has a significant impact on the composition of the microbiota no dietary intervention to date has proven effective for induction of remission. The investigators hypothesized that ulcerative colitis is caused by a series of events involving dysbiosis with sulfate or sulfide reducing bacteria combined with defective production of short chain fatty acids, coupled with a defective mucous layer.

Study Timeline

• Study First Submitted: 2015-01-19
• Study First Submitted QC: 2015-01-23
• Study First Posted: 2015-01-26
• Study Start: 2015-09-01
• Primary Completion: 2021-10-29
• Study Completion: 2021-10-29
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-29
• Last Update Posted: 2022-06-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Informed consent
2. Established diagnosis of UC.
3. Age: 8 - 19 years ( inclusive)
4. Mild to moderate active disease, 10 ≤ PUCAI ≤45.
5. Stable medication (IMM/ 5ASA) use for the past 6 weeks. Patients who have received topical 5ASA therapy for <7 days and are active may be included if topical therapy is stopped at enrolment

Exclusion Criteria

Exclusion criteria:

1. Any proven current infection such as positive stool culture, parasite or C. difficile.
2. Antibiotic or Steroids use in the past 2 weeks.
3. PUCAI >45
4. Acute severe UC in the previous 12 months.
5. Current Extra intestinal manifestation of UC.
6. PSC or Liver disease
7. Pregnancy.
8. Allergy to one of the antibiotics or age <11 will exclude patients from entering the antibiotic arm

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ulcerative Colitis Diet	Ulcerative Colitis Diet	Patients will receive a structured novel diet termed the UCD for 6 weeks, and those in remission at week 6 will receive the step down diet for another 6 weeks.
Antibiotic Treatment	Antibiotic cocktail	This antibiotic treatment will be given as an open label for patients who refuse diet therapy or for patients who show no improvement by week 3 , deteriorate by week 6, or patients who are not in full remission by week 6 will receive a 14 day course of antibiotics as previously described by Kato and colleagues.

Primary Outcome Measures

Name	Time	Method
Remission rate, defined as a PUCAI less than 10 at week 6.	week 6

Secondary Outcome Measures

Name	Time	Method
Physicians Global Assessment week 6	week 6
Remission week 12, defined as a PUCAI less than 10	week 12
Mean PUCAI week 12	week 12
Mean PUCAI week 6	week 6
Mean Calprotectin at week 6	week 6

Trial Locations

Locations (3)

The E. Wolfson.Medical Center; 🇮🇱 Holon, Israel

IWK Health Centre, Dalhousie University; 🇨🇦 Halifax, Nova Scotia, Canada

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States