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 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.

Patients, treating physician and study investigators will be blinded to the treatment intervention (FMT/ placebo).

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).

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.

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.

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.

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

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

determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in clinical response rate (reduction in HBI≥3 )

determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in reduction in HBI≥3

determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in reduction in HBI≥3

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

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

determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in histological healing compared to week 0

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

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

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

determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is safe and results in lower adverse events rate of intervention versus placebo

Inclusion Criteria: Mild-moderately active disease determined by the Harvey-Bradshaw index (HBI) of 5≤HBI≤15 Found eligible to commence treatment with vedolizumab (screened for tuberculosis and hepatitis B and without an active infection or an abscess) Exclusion Criteria: CD patients in remission (HBI<5) or with sever disease (HBI>16) Patients with a stoma Hospitalized patients Patients with an active intestinal infection- positive stool culture or Clostridium difficile infection Severe disease - malignant disease, hepatic failure, renal failure, cardiovascular, metabolic, neurological disease Pregnant/lactating women Inability to sign an informed consent Inability to complete the study protocol An ongoing or planned antibiotics therapy Severe food allergies