Manipulating the Microbiome in IBD by Antibiotics and FMT (FMT)

• ClinicalTrials.gov Identifier: NCT02033408
• Recruitment Status: Completed
• First Posted: January 10, 2014
• Last Update Posted: October 8, 2021
• Sponsor: Shaare Zedek Medical Center
• Information provided by (Responsible Party): Shaare Zedek Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Exacerbation of Ulcerative Colitis; Ulcerative Colitis, Active Severe; Crohn's Colitis	Drug: AB (antibiotics); Drug: CS (corticosteroids) Only	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Manipulating the Microbiome in IBD by Antibiotics and Fecal Microbiota Transplantation (FMT): a Randomized Controlled Trial
• Study Start Date: January 2014
• Actual Primary Completion Date: December 2018
• Actual Study Completion Date: January 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: AB (antibiotics); PO Vancomycin 250mgX4/d for 3 weeks; PO Amoxycillin 50mg/Kg divided by 3 (up to 500mgX3/d) - for 3 weeks; PO Doxycycline 2mg/kg X2/d (up to 100mgX2/d) - for 3 weeks; OR- For children younger than 8 years: PO Ciprofloxacin 10mg/Kg X2/2 (up to 250mgX2/d) for 3 weeks Patients with known allergy to one of the drugs may be treated with oral Gentamycin (2.5mg/KgX3/d) for 3 weeks instead of the allergenic drug.; Other Names: Ciprofloxacin-Ciprodex®; Doxycycline-Doxylin®; Gentamycin-Gentamicin®; Amoxicillin-Amoxyclav®; Vancomycin-Vanco-Teva®
Active Comparator: Steroids only; methylprednisolone-1.5mg/kg up to 60mg daily in two divided doses	Drug: CS (corticosteroids) Only; methylprednisolone (1.5mg/kg up to 60mg daily in two divided doses); PO Metronidazole 5mg/Kg X3/d (up to 250mgX3/d) - for 3 weeks; Other Name: Metronidazole-Flagyl®
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	Drug: AB (antibiotics); PO Vancomycin 250mgX4/d for 3 weeks; PO Amoxycillin 50mg/Kg divided by 3 (up to 500mgX3/d) - for 3 weeks; PO Doxycycline 2mg/kg X2/d (up to 100mgX2/d) - for 3 weeks; OR- For children younger than 8 years: PO Ciprofloxacin 10mg/Kg X2/2 (up to 250mgX2/d) for 3 weeks Patients with known allergy to one of the drugs may be treated with oral Gentamycin (2.5mg/KgX3/d) for 3 weeks instead of the allergenic drug.; Other Names: Ciprofloxacin-Ciprodex®; Doxycycline-Doxylin®; Gentamycin-Gentamicin®; Amoxicillin-Amoxyclav®; Vancomycin-Vanco-Teva®; Drug: CS (corticosteroids) Only; methylprednisolone (1.5mg/kg up to 60mg daily in two divided doses); PO Metronidazole 5mg/Kg X3/d (up to 250mgX3/d) - for 3 weeks; Other Name: Metronidazole-Flagyl®

Outcome Measures

Primary Outcome Measures :

1. Total PUCAI (Pediatric Ulcerative Colitis Activity Index) score [ Time Frame: at day 5 after treatment (compared between the two treatment groups). ]

Secondary Outcome Measures :

1. Remission rates [ Time Frame: 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.
2. Number of patients with PUCAI<35 points [ Time Frame: at day 5 ]
   without the need for second line therapy (anti TNF, cyclosporine or tacrolimus) or colectomy.
3. The need for second line therapy or colectomy by discharge [ Time Frame: by 90 days and at 1 year ]
4. Rate of steroid [ Time Frame: 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.
5. Need for subsequent admission [ Time Frame: by 1 year ]
6. Calprotectin levels [ Time Frame: at 5 and 14 days after treatment. ]
7. Rate of gastrointestinal carriage of resistant organisms (VRE, ESBL) [ Time Frame: at days 5 and 14 after treatment. ]
8. Change in microbiome pattern. [ Time Frame: 3 years from baseline ]
9. Rate of C. difficile infection [ Time Frame: at days 5 and 14 after treatment. ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Canada

The Hospital for Sick Children (SickKids)

Toronto, Canada

Finland

Hospital for Children and Adolescents Helsinki University Hospital

Helsinki, Finland

Israel

Soroka Medical Center

Beer Sheva, Israel

Rambam Medical Cener

Haifa, Israel

Wolfson Medical Center

Holon, Israel

Shaare Zedek Medical Center

Jerusalem, Israel, 9103102

Schneider Medical Center

Petach Tikva, Israel

Sheba Medical Center

Ramat Gan, Israel

Italy

Università degli Studi di Napoli "Federico II"

Napoli, Italy

Sapienza University of Rome

Rome, Italy

Poland

Univeristy Children's Hospital in Krakow

Krakow, Poland

Spain

Hospital Regional Universitario Carlos Haya Málaga

Malaga, Spain

Sponsors and Collaborators

Shaare Zedek Medical Center

Investigators

• Principal Investigator: Dan Turner, MD; Shaare Zedek Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Turner D, Bishai J, Reshef L, Abitbol G, Focht G, Marcus D, Ledder O, Lev-Tzion R, Orlanski-Meyer E, Yerushalmi B, Aloi M, Griffiths AM, Albenberg L, Kolho KL, Assa A, Cohen S, Gophna U, Vlamakis H, Lurz E, Levine A. Antibiotic Cocktail for Pediatric Acute Severe Colitis and the Microbiome: The PRASCO Randomized Controlled Trial. Inflamm Bowel Dis. 2020 Oct 23;26(11):1733-1742. doi: 10.1093/ibd/izz298.

• Responsible Party: Shaare Zedek Medical Center
• ClinicalTrials.gov Identifier: NCT02033408
• Other Study ID Numbers: ABCS-FMT-01
• First Posted: January 10, 2014
• Last Update Posted: October 8, 2021
• Last Verified: April 2019

Keywords provided by Shaare Zedek Medical Center:

IBD: Inflammatory Bowel Diseases; CD: Crohn's Disease; UC: Ulcerative Colitis; ASC: Acute Severe Colitis; FMT: Fecal Microbiota Transplantation; PUCAI: Pediatric Ulcerative Colitis Activity Index; Ciprofloxacin, Doxycycline, Gentamycin, amoxicillin, vancomycin, metronidazole,ciprofloxacin

Additional relevant MeSH terms:

Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Anti-Bacterial Agents; Amoxicillin; Metronidazole; Vancomycin; Doxycycline; Ciprofloxacin; Gentamicins; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors