Fecal Microbial Transplantation and Vedolizumab Treatment of Crohn's Disease

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Crohn Disease, Microbial Substitution

Intervention / Treatment
-----------------
* Other: Fecal microbial transplantation
* Other: Placebo capsuls


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized double blinded controlled clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fecal microbial transplantation<br>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<br>* Capsules of fecal matter solution (feces from healthy donor, glycerol and saline solution)/<br>|
| Placebo Comparator: Placebo<br>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<br>* capsules of glycerol and saline (placebo).<br>|

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 |