Clinical trial NCT02345733: Use of a Novel Diet (UC DIET) for Treatment of Mild to Moderate Active Pediatric Ulcerative Colitis
Official title: Use of a Novel Diet (UC DIET) Targeting the Microbiota for Treatment of Mild to Moderate Active Pediatric Ulcerative Colitis: An Open Label Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ulcerative Colitis (UC)
Lead sponsor: Wolfson Medical Center
Sponsor class: OTHER_GOV
First posted: 2015-01-26
Enrollment: 20
Sex: ALL
Minimum age (years): 8
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Remission rate, defined as a PUCAI less than 10 at week 6.
timeFrame: week 6
Secondary outcomes:
measure: Mean PUCAI week 6
timeFrame: week 6
measure: Mean Calprotectin at week 6
timeFrame: week 6
measure: Physicians Global Assessment week 6
timeFrame: week 6
measure: Remission week 12, defined as a PUCAI less than 10
timeFrame: week 12
measure: Mean PUCAI week 12
timeFrame: week 12
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Halifax
country: Canada
facility: IWK Health Centre, Dalhousie University
state: Nova Scotia
city: Holon
country: Israel
facility: The E. Wolfson.Medical Center
Study officials:
affiliation: Wolfson Medical Center
name: Arie Levine, MD
role: PRINCIPAL_INVESTIGATOR
References: