Clinical trial NCT02033408: Manipulating the Microbiome in IBD by Antibiotics and FMT
Official title: Manipulating the Microbiome in IBD by Antibiotics and Fecal Microbiota Transplantation (FMT): a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Shaare Zedek Medical Center
Sponsor class: OTHER
First posted: 2014-01-10
Enrollment: 28
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Total PUCAI (Pediatric Ulcerative Colitis Activity Index) score
timeFrame: at day 5 after treatment (compared between the two treatment groups).
Secondary outcomes:
measure: Remission rates
timeFrame: at days 7, separately at discharge, separately at day 14, and separately at 90 days.
measure: Number of patients with PUCAI<35 points
timeFrame: at day 5
measure: The need for second line therapy or colectomy by discharge
timeFrame: by 90 days and at 1 year
measure: Rate of steroid
timeFrame: dependency at 1 year
measure: Need for subsequent admission
timeFrame: by 1 year
measure: Calprotectin levels
timeFrame: at 5 and 14 days after treatment.
measure: Rate of gastrointestinal carriage of resistant organisms (VRE, ESBL)
timeFrame: at days 5 and 14 after treatment.
measure: Change in microbiome pattern.
timeFrame: 3 years from baseline
measure: Rate of C. difficile infection
timeFrame: at days 5 and 14 after treatment.
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children (SickKids)
city: Helsinki
country: Finland
facility: Hospital for Children and Adolescents Helsinki University Hospital
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Cener
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tikva
country: Israel
facility: Schneider Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Napoli
country: Italy
facility: Università degli Studi di Napoli "Federico II"
city: Rome
country: Italy
facility: Sapienza University of Rome
city: Krakow
country: Poland
facility: Univeristy Children's Hospital in Krakow
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya Málaga
Study officials:
affiliation: Shaare Zedek Medical Center
name: Dan Turner, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.