Ulcerative Colitis (UC)
Conditions
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.
Interventions
we have postulated that a diet that we developed that reduces exposure to dietary ingredients that allow sulfide reducing bacteria to thrive, or that impair the mucous layer, coupled with dietary products that enhance butyrate production, could induce remission in UC without involving additional immune suppression.
We have postulating that antibiotic therapy can alter the microbiota clinically. Controlling the microbiota by antibiotics may allow for control of the disease without immune suppression
Sponsors
Prof. Arie Levine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 19 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Remission rate, defined as a PUCAI less than 10 at week 6. | week 6 |
Secondary
| Measure | Time frame |
|---|---|
| Mean PUCAI week 6 | week 6 |
| Mean Calprotectin at week 6 | week 6 |
| 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 |
Countries
Canada, Israel, United States
Outcome results
None listed