Manipulating the Microbiome in IBD by Antibiotics and FMT

NCT ID: NCT02033408

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2021-01-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Antibiotics in addition to steroids

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

Group Type: EXPERIMENTAL

AB (antibiotics)

Intervention Type: 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.

Steroids only

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

Group Type: ACTIVE_COMPARATOR

CS (corticosteroids) Only

Intervention Type: 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

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

Group Type: OTHER

AB (antibiotics)

Intervention Type: 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.

CS (corticosteroids) Only

Intervention Type: 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

Interventions

AB (antibiotics)

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.

Intervention Type: DRUG

CS (corticosteroids) Only

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

Intervention Type: DRUG

Other Intervention Names

Ciprofloxacin-Ciprodex®; Doxycycline-Doxylin®; Gentamycin-Gentamicin®; Amoxicillin-Amoxyclav®; Vancomycin-Vanco-Teva®; Metronidazole-Flagyl®

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shaare Zedek Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dan Turner, MD

Role: PRINCIPAL_INVESTIGATOR

Shaare Zedek Medical Center

Locations

The Hospital for Sick Children (SickKids)

Toronto, , Canada

Hospital for Children and Adolescents Helsinki University Hospital

Helsinki, , Finland

Soroka Medical Center

Beersheba, , Israel

Rambam Medical Cener

Haifa, , Israel

Wolfson Medical Center

Holon, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Schneider Medical Center

Petah Tikva, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Università degli Studi di Napoli "Federico II"

Napoli, , Italy

Sapienza University of Rome

Rome, , Italy

Univeristy Children's Hospital in Krakow

Krakow, , Poland

Hospital Regional Universitario Carlos Haya Málaga

Málaga, , Spain

Countries

Canada; Finland; Israel; Italy; Poland; Spain

References

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.

Reference Type: DERIVED

PMID: 31833543 (View on PubMed)

Other Identifiers

ABCS-FMT-01

Identifier Type: -

Identifier Source: org_study_id