Fecal Microbial Transplantation and Vedolizumab Treatment of Crohn's Disease

Fecal Microbial Transplantation for the Optimization of Vedolizumab Treatment in Patients With Crohn's Disease

The investigators postulate that by determining a patient's baseline microbiome and manipulating it through fecal microbial transplantation (FMT) may improve response rates to vedolizumab in Crohn's disease (CD) patients.

Primary objective: To determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is safe and results in higher remission rates in CD patients.

Study design: A randomized double blinded controlled clinical trial. Study population:CD patients 18-65 YO, men and women, with mild-moderately active disease determined by the Harvey-Bradshaw index (HBI) of 5≤HBI≤15, who were found eligible to commence treatment with vedolizumab.

Study procedure: Study participants will receive FMT within a week prior to first vedolizumab infusion.

All patients will be followed for 46 weeks in 8 visits at the IBD clinic in the GI department of the Tel Aviv Medical Center.

Study Overview

• Status: Unknown
• Conditions: Crohn Disease; Microbial Substitution
• Intervention / Treatment: Other: Fecal microbial transplantation; Other: Placebo capsuls

Detailed Description

Study design: A randomized double blinded controlled clinical trial.

Study population:

CD patients 18-65 YO, men and women, with mild-moderately active disease determined by the Harvey-Bradshaw index (HBI) of 5≤HBI≤15, who were found eligible to commence treatment with vedolizumab (screened for tuberculosis and hepatitis B and without an active infection or an abscess) will be enrolled in the study.

Follow-up: All patients will be followed by physician assessment, sample collection, anthropometric measurements and questionnaires during the scheduled visits at weeks 2, 6, 14, 22, and at week 46, on which they will undergo a colonoscopic examination as part of their regular clinical followup.

Side effects (SE): will be monitored by phone, 3 days post intervention and at vedolizumab infusion visits at weeks 2 and 6. Also, patients will receive direct contact details of both the study coordinator and the study PI.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel, 64239
    • Recruiting
    • Department of Gastroentherology
    • Principal Investigator: Nitsan Maharshak, MD
    • Sub-Investigator: Naomi Fliss Isakov, PhD
    • Contact: Nitsan Maharshak, MD; Phone Number: 972-3-6972488; Email: nitsanm@tlvmc.gov.il
    • Sub-Investigator: Nethaniel Aviv Cohen, MD
  • Tel Aviv, Israel
    • Recruiting
    • Dep. of Gastroenterology, Tel Aviv Sourasky Medical Center
    • Principal Investigator: Nitsan Maharshak, MD
    • Sub-Investigator: Naomi Fliss Isakov, PhD
    • Contact: Nitsan Maharshak, MD; Phone Number: 972-3-6947305; Email: nitsanm@tlvmc.gov.il
    • Sub-Investigator: Nathaniel Aviv Cohen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Mild-moderately active disease determined by the Harvey-Bradshaw index (HBI) of 5≤HBI≤15
2. Found eligible to commence treatment with vedolizumab (screened for tuberculosis and hepatitis B and without an active infection or an abscess)

Exclusion Criteria:

1. CD patients in remission (HBI<5) or with sever disease (HBI>16)
2. Patients with a stoma
3. Hospitalized patients
4. Patients with an active intestinal infection- positive stool culture or Clostridium difficile infection
5. Severe disease - malignant disease, hepatic failure, renal failure, cardiovascular, metabolic, neurological disease
6. Pregnant/lactating women
7. Inability to sign an informed consent
8. Inability to complete the study protocol
9. An ongoing or planned antibiotics therapy
10. Severe food allergies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fecal microbial transplantation; FMT capsules fecal capsules on two consecutive days (total of 30 capsules) within a week prior to first vedolizumab infusion. Patients who will be allocated to this treatment arm will be matched to donors according to their CMV status (past exposure - CMV positive donors will be used for CMV positive patients, and CMV negative donors will be used for CMV negative patients).	Other: Fecal microbial transplantation; Capsules of fecal matter solution (feces from healthy donor, glycerol and saline solution)/
Placebo Comparator: Placebo; Placebo capsules placebo capsules- on two consecutive days (total of 30 capsules) within a week prior to first vedolizumab infusion. Patients who will be allocated to this treatment arm will receive placebo capsules.	Other: Placebo capsuls; capsules of glycerol and saline (placebo).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety of FMT pre vedolizumab treatment in CD patients	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is safe. safety of FMT will be measured by disease exacerbations, hospitalizations and surgery rate in treatment versus placebo group.	week 14
safety of FMT pre vedolizumab treatment in CD patients: measured by disease exacerbations, hospitalizations and surgery rate in treatment versus placebo group	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is safe. safety of FMT will be measured by disease exacerbations, hospitalizations and surgery rate in treatment versus placebo group.	week 46
efficacy of FMT pre vedolizumab treatment in CD patients that results in higher remission rate	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in higher remission rates in CD patients. Remission rate will be measured by clinical remission rate HBI ≤5 at week 14	week 14
efficacy of FMT pre vedolizumab treatment in CD patients that results in higher remission rate	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in higher remission rates in CD patients. Remission rate will be measured by clinical remission rate HBI ≤5 at week 46	week 46

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy of FMT pre vedolizumab treatment in CD patients that results in clinical response rate	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in clinical response rate (reduction in HBI≥3 )	week 14
efficacy of FMT pre vedolizumab treatment in CD patients that results in clinical response rate	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in reduction in HBI≥3	week 22
efficacy of FMT pre vedolizumab treatment in CD patients that results in clinical response rate	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in reduction in HBI≥3	week 46
efficacy of FMT pre vedolizumab treatment in CD patients that results in endoscopic response	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in endoscopic response that will be defined as a decrease of ≥50% in SES-CD score / improvement in Rutgeerts score ≥1, compared to baseline colonoscopy	week 46
efficacy of FMT pre vedolizumab treatment in CD patients that results in endoscopic remission	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in Endoscopic remission at week 46 will be defined as SES-CD ≤2 or Rutgeerts score ≤1 , compared to baseline colonoscopy	week 46
efficacy of FMT pre vedolizumab treatment in CD patients that results in histological healing	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in histological healing compared to week 0	week 46
efficacy of FMT pre vedolizumab treatment in CD patients that results in biological remission	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in biological remission measured as fecal calprotectin<150mg/kg and CRP<5mg/L	week 14
efficacy of FMT pre vedolizumab treatment in CD patients that results in biological remission	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in biological remission measured as fecal calprotectin<150mg/kg and CRP<5mg/L	week 22
efficacy of FMT pre vedolizumab treatment in CD patients that results in biological remission	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in biological remission measured as fecal calprotectin<150mg/kg and CRP<5mg/L	week 46
safety of FMT pre vedolizumab treatment in CD patients that results in low adverse events rate	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is safe and results in lower adverse events rate of intervention versus placebo	week 46

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2018
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: February 8, 2019
• First Submitted That Met QC Criteria: March 31, 2020
• First Posted (Actual): April 1, 2020

Study Record Updates

• Last Update Posted (Actual): April 1, 2020
• Last Update Submitted That Met QC Criteria: March 31, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: TASMC-16-NH-0123-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No