search
Back to results

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

Primary Purpose

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

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
AB (antibiotics)
CS (corticosteroids) Only
Sponsored by
Shaare Zedek Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Exacerbation of Ulcerative Colitis focused on measuring 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

Eligibility Criteria

2 Years - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Hospital for Sick Children (SickKids)
  • Hospital for Children and Adolescents Helsinki University Hospital
  • Soroka Medical Center
  • Rambam Medical Cener
  • Wolfson Medical Center
  • Shaare Zedek Medical Center
  • Schneider Medical Center
  • Sheba Medical Center
  • Università degli Studi di Napoli "Federico II"
  • Sapienza University of Rome
  • Univeristy Children's Hospital in Krakow
  • Hospital Regional Universitario Carlos Haya Málaga

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Other

Arm Label

Antibiotics in addition to steroids

Steroids only

Open arm

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Total PUCAI (Pediatric Ulcerative Colitis Activity Index) score

Secondary Outcome Measures

Remission rates
defined by PUCAI<10 without the need for second line therapy (anti TNF (Tumor Necrosis Factor), cyclosporine or tacrolimus) or colectomy.
Number of patients with PUCAI<35 points
without the need for second line therapy (anti TNF, cyclosporine or tacrolimus) or colectomy.
The need for second line therapy or colectomy by discharge
Rate of steroid
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
Calprotectin levels
Rate of gastrointestinal carriage of resistant organisms (VRE, ESBL)
Change in microbiome pattern.
Rate of C. difficile infection

Full Information

First Posted
December 3, 2013
Last Updated
September 30, 2021
Sponsor
Shaare Zedek Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT02033408
Brief Title
Manipulating the Microbiome in IBD by Antibiotics and FMT
Acronym
FMT
Official Title
Manipulating the Microbiome in IBD by Antibiotics and Fecal Microbiota Transplantation (FMT): a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
January 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shaare Zedek Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Antibiotics in addition to steroids
Arm Type
Experimental
Arm Description
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
Arm Title
Steroids only
Arm Type
Active Comparator
Arm Description
methylprednisolone-1.5mg/kg up to 60mg daily in two divided doses
Arm Title
Open arm
Arm Type
Other
Arm Description
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 Type
Drug
Intervention Name(s)
AB (antibiotics)
Other Intervention Name(s)
Ciprofloxacin-Ciprodex®, Doxycycline-Doxylin®, Gentamycin-Gentamicin®, Amoxicillin-Amoxyclav®, Vancomycin-Vanco-Teva®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
CS (corticosteroids) Only
Other Intervention Name(s)
Metronidazole-Flagyl®
Intervention Description
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
Primary Outcome Measure Information:
Title
Total PUCAI (Pediatric Ulcerative Colitis Activity Index) score
Time Frame
at day 5 after treatment (compared between the two treatment groups).
Secondary Outcome Measure Information:
Title
Remission rates
Description
defined by PUCAI<10 without the need for second line therapy (anti TNF (Tumor Necrosis Factor), cyclosporine or tacrolimus) or colectomy.
Time Frame
at days 7, separately at discharge, separately at day 14, and separately at 90 days.
Title
Number of patients with PUCAI<35 points
Description
without the need for second line therapy (anti TNF, cyclosporine or tacrolimus) or colectomy.
Time Frame
at day 5
Title
The need for second line therapy or colectomy by discharge
Time Frame
by 90 days and at 1 year
Title
Rate of steroid
Description
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.
Time Frame
dependency at 1 year
Title
Need for subsequent admission
Time Frame
by 1 year
Title
Calprotectin levels
Time Frame
at 5 and 14 days after treatment.
Title
Rate of gastrointestinal carriage of resistant organisms (VRE, ESBL)
Time Frame
at days 5 and 14 after treatment.
Title
Change in microbiome pattern.
Time Frame
3 years from baseline
Title
Rate of C. difficile infection
Time Frame
at days 5 and 14 after treatment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Turner, MD
Organizational Affiliation
Shaare Zedek Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Hospital for Sick Children (SickKids)
City
Toronto
Country
Canada
Facility Name
Hospital for Children and Adolescents Helsinki University Hospital
City
Helsinki
Country
Finland
Facility Name
Soroka Medical Center
City
Beer Sheva
Country
Israel
Facility Name
Rambam Medical Cener
City
Haifa
Country
Israel
Facility Name
Wolfson Medical Center
City
Holon
Country
Israel
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
ZIP/Postal Code
9103102
Country
Israel
Facility Name
Schneider Medical Center
City
Petach Tikva
Country
Israel
Facility Name
Sheba Medical Center
City
Ramat Gan
Country
Israel
Facility Name
Università degli Studi di Napoli "Federico II"
City
Napoli
Country
Italy
Facility Name
Sapienza University of Rome
City
Rome
Country
Italy
Facility Name
Univeristy Children's Hospital in Krakow
City
Krakow
Country
Poland
Facility Name
Hospital Regional Universitario Carlos Haya Málaga
City
Malaga
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
31833543
Citation
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.
Results Reference
derived

Learn more about this trial

Manipulating the Microbiome in IBD by Antibiotics and FMT

We'll reach out to this number within 24 hrs