Crohn Disease, Microbial Substitution
Conditions
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.
Interventions
Capsules of fecal matter solution (feces from healthy donor, glycerol and saline solution)/
OTHERPlacebo capsuls
capsules of glycerol and saline (placebo).
Sponsors
Tel-Aviv Sourasky Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patients, treating physician and study investigators will be blinded to the treatment intervention (FMT/ placebo).
Intervention model description
A randomized double blinded controlled clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| efficacy of FMT pre vedolizumab treatment in CD patients that results in higher remission rate | 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 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 clinical response rate | week 14 | determine whether manipulation of gut microbiome by FMT pre vedolizumab treatment is efficient and results in clinical response rate (reduction in HBI≥3 ) |
| 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 biological remission | week 14 | 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 |
| 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 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 |
Countries
Israel
Outcome results
None listed