Manipulating the Microbiome in IBD by Antibiotics and FMT

Not Applicable

Completed

• Conditions: Exacerbation of Ulcerative Colitis; Crohn's Colitis; Ulcerative Colitis, Active Severe
• Interventions: Drug: CS (corticosteroids) Only; Drug: AB (antibiotics)

• Registration Number: NCT02033408
• Lead Sponsor: Shaare Zedek Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-12-03
• Study Start: 2014-01
• Study First Submitted QC: 2014-01-09
• Study First Posted: 2014-01-10
• Primary Completion: 2018-12
• Status Verified: 2019-04
• Study Completion: 2021-01
• Last Update Submitted: 2021-09-30
• Last Update Posted: 2021-10-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Steroids only	CS (corticosteroids) Only	methylprednisolone-1.5mg/kg up to 60mg daily in two divided doses
Antibiotics in addition to steroids	AB (antibiotics)	methylprednisolone-1.5mg/kg up to 60mg daily in two divided doses and in addition the following antibiotics: 1. PO Vancomycin 250mg 4 times a day for 3 weeks (children under age 8 125mgX4/d for 3 weeks) 2. PO Amoxycillin 50mg per Kg divided by 3 (up to 500mg 3 times a day) - for 3 weeks 3. PO Metronidazole 5mg per Kg 3 times a day (up to 250mg 3 times a day) - for 3 weeks 4. 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
Open arm	AB (antibiotics)	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
Open arm	CS (corticosteroids) Only	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

Primary Outcome Measures

Name	Time	Method
Total PUCAI (Pediatric Ulcerative Colitis Activity Index) score	at day 5 after treatment (compared between the two treatment groups).

Secondary Outcome Measures

Name	Time	Method
Number of patients with PUCAI<35 points	at day 5	without the need for second line therapy (anti TNF, cyclosporine or tacrolimus) or colectomy.
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.	defined by PUCAI\<10 without the need for second line therapy (anti TNF (Tumor Necrosis Factor), cyclosporine or tacrolimus) or colectomy.
The need for second line therapy or colectomy by discharge	by 90 days and at 1 year
Rate of steroid	dependency at 1 year	defined as a course longer than 3 month with an unsuccessful attempt to wean steroids or cumulative steroid treatment months of 4 months, during the 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.

Trial Locations

Locations (12)

Soroka Medical Center; 🇮🇱 Beer Sheva, Israel

Rambam Medical Cener; 🇮🇱 Haifa, Israel

Hospital for Children and Adolescents Helsinki University Hospital; 🇫🇮 Helsinki, Finland

Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

The Hospital for Sick Children (SickKids); 🇨🇦 Toronto, Canada

Wolfson Medical Center; 🇮🇱 Holon, Israel

Univeristy Children's Hospital in Krakow; 🇵🇱 Krakow, Poland

Schneider Medical Center; 🇮🇱 Petach Tikva, Israel

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel

Università degli Studi di Napoli "Federico II"; 🇮🇹 Napoli, Italy

Hospital Regional Universitario Carlos Haya Málaga; 🇪🇸 Malaga, Spain

Sapienza University of Rome; 🇮🇹 Rome, Italy