Fecal Microbial Transplantation for Ileal Pouch Anal Anastomosis Patients

NCT ID: NCT04336319

Last Updated: 2020-04-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-05
• Study Completion Date: 2024-12-31

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.

Conditions

Ileal Pouch Anal Anastomosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with a confirmed diagnosis of UC who underwent IPAA

Patients who meet inclusion criteria will be enrolled and will sign an informed consent form. The study includes six visits to the IBD clinic and phone calls between visits.

Group Type: EXPERIMENTAL

Fecal Microbial Transplantation

Intervention Type: BIOLOGICAL

1. At baseline, the fecal fluid from 3 different donors, 150 ml, will be delivered via pouchoscopy after which the patient will roll in to the right lateral position and stay in that position for at least 15 minutes. Prior to the procedure, the patient will fast for 12 hours and preform two fleet enemas as preperation.

2. FMT at 7 days and 4 weeks will be delivered via ingestion of 15 capsules containing 650 µL of fecal fluid from 3 different donors (the same three donors as at baseline).

Interventions

Fecal Microbial Transplantation

1. At baseline, the fecal fluid from 3 different donors, 150 ml, will be delivered via pouchoscopy after which the patient will roll in to the right lateral position and stay in that position for at least 15 minutes. Prior to the procedure, the patient will fast for 12 hours and preform two fleet enemas as preperation.

2. FMT at 7 days and 4 weeks will be delivered via ingestion of 15 capsules containing 650 µL of fecal fluid from 3 different donors (the same three donors as at baseline).

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tel-Aviv Sourasky Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

michal roll

Director, R&D Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nitsan Maharshak, MD

Role: PRINCIPAL_INVESTIGATOR

Tel Aviv Medical Center

Locations

Dep. of Gastroenterology, Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Naomi Fliss, PhD

Role: CONTACT

naomifl@tlvmc.gov.il

97236974924

Meytal Kahlon, BA

Role: CONTACT

meytalkah@tlvmc.gov.il

97236974924

Facility Contacts

Nitsan Maharshak, PhD

Role: primary

nitsanm@tlvmc.gov.il

972-3-6947305

Other Identifiers

0210-18-TLV

Identifier Type: -

Identifier Source: org_study_id