Fecal Microbial Transplantation and Vedolizumab Treatment of Crohn's Disease

Not Applicable

• Conditions: Microbial Substitution; Crohn Disease
• Interventions: Other: Fecal microbial transplantation; Other: Placebo capsuls

• Registration Number: NCT04328922
• Lead Sponsor: Tel-Aviv Sourasky Medical Center

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.

Study Timeline

• Study Start: 2018-07-03
• Study First Submitted: 2019-02-08
• Status Verified: 2020-03
• Study First Submitted QC: 2020-03-31
• Last Update Submitted: 2020-03-31
• Study First Posted: 2020-04-01
• Last Update Posted: 2020-04-01
• Primary Completion: 2022-04
• Study Completion: 2023-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fecal microbial transplantation	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).
Placebo	Placebo capsuls	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.

Primary Outcome Measures

Name	Time	Method
safety of FMT pre vedolizumab treatment in CD patients	week 14	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.
efficacy of FMT pre vedolizumab treatment in CD patients that results in higher remission rate	week 46	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
safety of FMT pre vedolizumab treatment in CD patients: measured by disease exacerbations, hospitalizations and surgery rate in treatment versus placebo group	week 46	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.

Secondary Outcome Measures

Name	Time	Method
efficacy of FMT pre vedolizumab treatment in CD patients that results in clinical response rate	week 46	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in reduction in HBI≥3
efficacy of FMT pre vedolizumab treatment in CD patients that results in biological remission	week 46	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
safety of FMT pre vedolizumab treatment in CD patients that results in low adverse events rate	week 46	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is safe and results in lower adverse events rate of intervention versus placebo
efficacy of FMT pre vedolizumab treatment in CD patients that results in endoscopic response	week 46	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
efficacy of FMT pre vedolizumab treatment in CD patients that results in histological healing	week 46	determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in histological healing compared to week 0
efficacy of FMT pre vedolizumab treatment in CD patients that results in endoscopic remission	week 46	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

Trial Locations

Locations (2)

Department of Gastroentherology; 🇮🇱 Tel Aviv, Israel

Dep. of Gastroenterology, Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel