Manipulating the Microbiome in IBD by Antibiotics and Fecal Microbiota Transplantation (FMT): a Randomized Controlled Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Shaare Zedek Medical Center
- Enrollment
- 28
- Locations
- 12
- Primary Endpoint
- Total PUCAI (Pediatric Ulcerative Colitis Activity Index) score
Study Overview
Brief Summary
the etiology of Inflammatory Bowel Diseases (IBD) is closely associated with the gut microbiome. The results of previous studies on the effectiveness of antibiotics and fecal macrobiota transplantation (FMT) are contradicting.
Aims: to evaluate the effectiveness of wide-spectrum antibiotic regimens in acute severe colitis in an addition to standard corticosteroid therapy (UC and isolated "UC-like" Crohn's colitis). The secondary aim is to assess the outcome of FMT in those not responding to five days of therapy (in either arm). As an exploratory aim, any IBD patient with a resistant disease to at least two immunosuppressive medications, may be treated with either interventions.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Investigator)
Eligibility Criteria
- Ages
- 2 Years to 75 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Children over the age the 2 years and adults of all ages with established diagnosis of UC using standard criteria (26, 27).
- •Admission for IV steroid therapy
- •PUCAI of at least 65 points at admission (i.e. severe attack)
- •PUCAI>45 at enrollment
- •Ability to swallow antibiotics (pills or syrup)
Exclusion Criteria
- •Change in dose or intervals of anti-TNF within the past 2 months prior to admission.
- •Disease confined to the rectum (Proctitis).
- •Antibiotic use in the past 4 weeks.
- •Any known erosive inflammation anywhere in the small bowel or esophagus.
- •Any proven infection such as positive stool culture, parasite or C. difficile, urinary tract infection, cellulitis, abscess, pneumonia, line-infections etc.
- •Fever >38.5, or >38.0c thought to be unrelated to the inflammatory process of active UC.
- •The probable need for second line medical therapy (infliximab, cyclosporine, tacrolimus) or colectomy within 5 days of enrollment, as judged by the caring physician.
- •Known allergy to more than one antibiotic regimen from the list below.
- •Pregnancy.
Arms & Interventions
Antibiotics in addition to steroids
methylprednisolone-1.5mg/kg up to 60mg daily in two divided doses and in addition the following antibiotics:
- PO Vancomycin 250mg 4 times a day for 3 weeks (children under age 8 125mgX4/d for 3 weeks)
- PO Amoxycillin 50mg per Kg divided by 3 (up to 500mg 3 times a day) - for 3 weeks
- PO Metronidazole 5mg per Kg 3 times a day (up to 250mg 3 times a day) - for 3 weeks
- PO Doxycycline 2mg per kg twice a day (up to 100mg twice a day) - for 3 weeks; OR- For children younger than 7 years: PO Ciprofloxacin 10mg per Kg twice a day (up to 250mg twice a day) for 3 weeks
Intervention: AB (antibiotics) (Drug)
Steroids only
methylprednisolone-1.5mg/kg up to 60mg daily in two divided doses
Intervention: CS (corticosteroids) Only (Drug)
Open arm
either the antibiotics and/or FMT (fecal microbiome transplant) may be administered in a non-randomized, uncontrolled open-label arm to any resistant IBD patients
Intervention: AB (antibiotics) (Drug)
Open arm
either the antibiotics and/or FMT (fecal microbiome transplant) may be administered in a non-randomized, uncontrolled open-label arm to any resistant IBD patients
Intervention: CS (corticosteroids) Only (Drug)
Outcomes
Primary Outcomes
Total PUCAI (Pediatric Ulcerative Colitis Activity Index) score
Time Frame: at day 5 after treatment (compared between the two treatment groups).
Secondary Outcomes
- Number of patients with PUCAI<35 points(at day 5)
- Rate of gastrointestinal carriage of resistant organisms (VRE, ESBL)(at days 5 and 14 after treatment.)
- Remission rates(at days 7, separately at discharge, separately at day 14, and separately at 90 days.)
- The need for second line therapy or colectomy by discharge(by 90 days and at 1 year)
- Rate of steroid(dependency at 1 year)
- Need for subsequent admission(by 1 year)
- Calprotectin levels(at 5 and 14 days after treatment.)
- Change in microbiome pattern.(3 years from baseline)
- Rate of C. difficile infection(at days 5 and 14 after treatment.)