Clinical trial NCT04336319: Fecal Microbial Transplantation for Ileal Pouch Anal Anastomosis Patients
Official title: An Exploratory Pilot Study Assessing the Efficacy of Fecal Microbial Transplantation for Clinical and Endoscopic Characteristics of Ileal Pouch Anal Anastomosis Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ileal Pouch Anal Anastomosis
Keywords: POUCH
FMT
IPAA
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2020-04-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigator is hypothesize that an intensive FMT regimen will have superior efficacy the treatment of inflammatory disorders of the pouch (pouchitis and CLDP).

Detailed description: Study Design:

An open label non-controlled clinical trial.

Study population:

Patients aged 18 to 80 years with a confirmed diagnosis of UC , who underwent IPAA.

Recruitment of the study population:

Patients will be enrolled at the Pouch Clinic of the Tel Aviv Medical Center Inflammatory Bowel Disease Center and at the Department of Colorectal Surgery.

Study procedure:

The study includes six visits to the IBD clinic and phone calls between visits. At baseline, after 8 weeks and after one year of intervention, all patients will undergo pouchoscopy which will be recorded and scored for pouch endoscopic score (Appendix 2). In all three procedures, samples will be collected for future analysis.

According to their endoscopic evaluation at baseline, patients will be categorized as those with an inflamed pouch (cuff, afferent loop, pouch inlet, J-pouch, pouch outlet or pouch mid-line scare) or non inflamed pouch (irritable pouch patients) according to a pouch endoscopic score (PES) and the modified pouch disease activity index endoscopic domain (mPDAI).

Baseline pouchoscopy will include FMT, followed by capsule FMT after 1 week (15 capsules), and after 4 weeks of the study.

All patients will undergo clinical followup at week 4 of the study (mPDAI clinical domain, PCS and PGA) and a second pouchoscopy after 8 weeks.

Clinical follow up will be performed at week 12 of the study, and an annual endoscopic follow up will be preformed at 52 weeks or per personal indication.

Data collection at baseline and follow-up visits will include:

1. Clinical assessment:

   * Pouch clinical score (PCS)
   * mPDAI - clinical domains
   * Physician Global Assessment (PGA)
   * Pouch endoscopic score (PES)
2. Collection of biological samples:

   * Stool for analysis of calprotectin level and microbiome
   * Urine for analysis of metabolomics
   * Serum for analysis of complete blood count (CBC), serum levels of C-Reactive Protein (CRP), albumin, creatinine, liver enzymes
   * Tissue samples collected during pouchoscopy at baseline and followup - samples will be collected from the cuff, pouch body and pouch inlet.
3. Anthropocentric measures will be assessed (weight, height)
4. Complete study questionnaires:

   * A validated lifestyle and food frequency questionnaire (FFQ)
   * Three day food diary
   * Quality of life questionnaire (SF-12)
   * Patient-reported outcomes (PRO) Measurement Information System (PROMIS)
   * Life style questionnaire

Safety assessments:

will include history taking, vital signs, physical examinations and laboratory analysis during each visit. Patients who discontinue the trial treatment will continue to be followed as per protocol. Follow-up will be discontinued in patients who withdraw informed consent or are lost for follow-up. All adverse events will be registered as: unrelated, possible related, likely related or definitely related to the intervention. SAEs will be communicated immediately to the IRB.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18 to 80 years with a confirmed diagnosis of UC, who underwent IPAA.
2. Endoscopic deterioration or Clinically suspected pouchitis, defined as increased bowel frequency (≥1 stools) relative to post-IPAA baseline (1-3 months post IPAA).
3. Clinically stable patients on constant medical regimen throughout the study period. Treated by mesalamine for at least 6 weeks, or steroids at least 2 week, or immunomodulator or biologic at least 12 weeks, medical cannabis at least 2 weeks

Exclusion Criteria:

1. Diagnosis of Crohn's disease or indeterminate colitis prior to IPAA.
2. Positive stool test for parasites or stool culture for pathological bacteria within 60 days prior to enrollment.
3. Evidence or history of Clostridium difficile infection within 60 days prior to enrollment.
4. Active clinically significant infection (within 60 days of enrollment).
5. Active septic pouch complication (e.g., abscess, leak, fistula).
6. Post-surgical complication of the pouch (e.g., obstruction, stricture, volvulus, prolapse).
7. Pregnancy or lactation.
8. Unstable or uncontrolled medical disorder (other than suspected pouchitis).
9. Inability to give informed consent and complete the study protocol.
10. Patient participating in other concomitant clinical intervention trial or who had received any experimental drug within a month prior to enrollment
11. Patients received antibiotics within 2 days of enrollment, or are anticipated to use antibiotics or probiotics within the study period (elective surgery or dental care).
12. Patients received fecal transplantation in the last 6 months.
13. Fever\>38°c
14. An active malignant disease or a prior malignancy during the previous 5 years (excluding skin BCC).
15. Inability or reluctance to follow through with the study protocol, including (but not exclusive) to: colonoscopy, enema, study visit.

Primary outcomes:
measure: safety of fecal microbial transplantation in pouch patients by disease exacerbations
timeFrame: 1 year
measure: safety of fecal microbial transplantation in pouch patients by hospitalizations of patients
timeFrame: 1 year
measure: safety of fecal microbial transplantation in pouch patients by patients requiring surgery
timeFrame: 1 year
measure: efficacy of FMT in pouch patients measured by mPDAI decrease
timeFrame: 2 months
measure: efficacy of FMT in pouch patients measured by clinical remission
timeFrame: 2 months
Secondary outcomes:
measure: efficacy of FMT in pouch patients measured by amount of patients with sustained remission
timeFrame: 12 months
measure: efficacy of FMT in pouch patients measured by amount of patients with sustained clinical remission
timeFrame: 12 months
measure: efficacy of FMT in pouch patients measured by reduce of inflammatory markers
timeFrame: 1 month
measure: efficacy of FMT in pouch patients measured by reduce of inflammatory markers
timeFrame: 2 months
measure: efficacy of FMT in pouch patients measured by reduce of inflammatory markers
timeFrame: 3 months
measure: efficacy of FMT in pouch patients measured by reduce of inflammatory markers
timeFrame: 12 months
measure: efficacy of FMT in pouch patients measured by reduce of PGA (physical global assessment)
timeFrame: 1 month
measure: efficacy of FMT in pouch patients measured by reduce of PGA (physical global assessment)
timeFrame: 2 months
measure: efficacy of FMT in pouch patients measured by reduce of PGA (physical global assessment)
timeFrame: 3 months
measure: efficacy of FMT in pouch patients measured by reduce of PGA (physical global assessment)
timeFrame: 12 months
measure: efficacy of FMT in pouch patients measured by improvement of life quality
timeFrame: 1 month
measure: efficacy of FMT in pouch patients measured by improvement of life quality
timeFrame: 2 months
measure: efficacy of FMT in pouch patients measured by improvement of life quality
timeFrame: 3 months
measure: efficacy of FMT in pouch patients measured by improvement of life quality
timeFrame: 12 months
measure: efficacy of FMT in pouch patients measured by improvement of nutritional status
timeFrame: 1 month
measure: efficacy of FMT in pouch patients measured by improvement of nutritional status
timeFrame: 2 months
measure: efficacy of FMT in pouch patients measured by improvement of nutritional status
timeFrame: 3 months
measure: efficacy of FMT in pouch patients measured by improvement of nutritional status
timeFrame: 12 months
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Dep. of Gastroenterology, Tel Aviv Sourasky Medical Center
Study officials:
affiliation: Tel Aviv Medical Center
name: Nitsan Maharshak, MD
role: PRINCIPAL_INVESTIGATOR
References: