Manipulating the Microbiome in IBD by Antibiotics and FMT

NCT02033408 | Completed DMC

• 1 other identifier: ABCS-FMT-01
• Study Type: interventional
• Target: 28
• Locations: 6 countries
• Sites: 12

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.

Conditions

Exacerbation of Ulcerative Colitis; Ulcerative Colitis, Active Severe; Crohn's Colitis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Total PUCAI (Pediatric Ulcerative Colitis Activity Index) score

  at day 5 after treatment (compared between the two treatment groups).

Secondary Outcomes (9)

• Remission rates

  at days 7, separately at discharge, separately at day 14, and separately at 90 days.

• Number of patients with PUCAI<35 points

  at day 5

• 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

Study Arms (3)

Antibiotics in addition to steroids

EXPERIMENTAL

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

Drug: AB (antibiotics)

Steroids only

ACTIVE COMPARATOR

methylprednisolone-1.5mg/kg up to 60mg daily in two divided doses

Drug: CS (corticosteroids) Only

Open arm

OTHER

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); Drug: CS (corticosteroids) Only

Interventions

AB (antibiotics) DRUG

1. PO Vancomycin 250mgX4/d for 3 weeks 2. PO Amoxycillin 50mg/Kg divided by 3 (up to 500mgX3/d) - for 3 weeks 3. 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.

Also known as: Ciprofloxacin-Ciprodex®, Doxycycline-Doxylin®, Gentamycin-Gentamicin®, Amoxicillin-Amoxyclav®, Vancomycin-Vanco-Teva®

Antibiotics in addition to steroids; Open arm

CS (corticosteroids) Only DRUG

1. methylprednisolone (1.5mg/kg up to 60mg daily in two divided doses) 2. PO Metronidazole 5mg/Kg X3/d (up to 250mgX3/d) - for 3 weeks

Also known as: Metronidazole-Flagyl®

Open arm; Steroids only

Eligibility Criteria

• Age: 2 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shaare Zedek Medical Center: lead

Study Sites (12)

The Hospital for Sick Children (SickKids)

Toronto, Canada

Location

Hospital for Children and Adolescents Helsinki University Hospital

Helsinki, Finland

Location

Soroka Medical Center

Beersheba, Israel

Location

Rambam Medical Cener

Haifa, Israel

Location

Wolfson Medical Center

Holon, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Schneider Medical Center

Petah Tikva, Israel

Location

Sheba Medical Center

Ramat Gan, Israel

Location

Università degli Studi di Napoli "Federico II"

Napoli, Italy

Location

Sapienza University of Rome

Rome, Italy

Location

Univeristy Children's Hospital in Krakow

Krakow, Poland

Location

Hospital Regional Universitario Carlos Haya Málaga

Málaga, Spain

Location

Related Publications (1)

• 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.

  PMID: 31833543 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative; Crohn Disease

Interventions

Anti-Bacterial Agents; Adrenal Cortex Hormones; Single Person

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors

Study Officials

• Dan Turner, MD

  Shaare Zedek Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2013
• First Posted: January 10, 2014
• Study Start: January 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: January 1, 2021
• Last Updated: October 8, 2021

Record last verified: 2019-04

Locations

IT (2); FI (1); PL (1); IL (6); CA (1); ES (1)