Safety and Efficacy of Heterologous FMT by SQIMC-md Capsule in Mild-moderate Ulcerative Colitis Patients (SQIMC-md)

Safety and Efficacy of Heterologous Fecal Microbiota Transplantation (FMT) by Standardized Quantitative Multi-donor Intestinal Microbiota Capsule (SQIMC-md) in Mild-moderate Ulcerative Colitis Patients-a Multi-center Double-blind RCT Trial

This study aims to assess the safety and efficacy of heterologous fecal microbiota transplantation (FMT) by Standardized Quantitative multi-donor Intestinal Microbiota Capsule (SQIMC-md) in mild-moderate ulcerative colitis patients who fail to achieve clinical remission over 4 weeks after full dose 5-Aminosalicylic acid(5-ASA). Intestinal microbiota transplant for FMT will be prepared from multiple healthy donors and prepared by standardized procedure with fixed quantitative dosage. This strategy might offer a novel and safe therapeutic approach for these patients before step up to corticosteroid, immunosuppressant or biologics therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Procedure: placebo capsule; Procedure: Standardized Quantitative multi-donor Intestinal Microbiota Capsule (SQIMC-md)

Detailed Description

All candidates for mild-moderate ulcerative colitis treated in Dept. Gastroenterology, Tongji Hospital, Tongji Medical College of HUST, the second Xiangya Hospital of central south university and the first affiliated Hospital of Zhengzhou University will be screened for study inclusion and exclusion criteria. All consenting patients will 2:1 randomized into SQIMC-md treatment group or Placebo group. Three dose of SQIMC-md capsule will be orally administrated on day1, day2 and day3. Follow-up will be performed every 4 weeks and last for 12weeks. Full dose of 5-ASA is orally administrated simultaneously during the study. Clinical data and outcome will be collected and documented in electronic case reported form (eCRF).

FMT DONORS:

Potential healthy adult stool donors (between 18 and 28 years of age) will be recruited by the research staff. They will be asked to volunteer for the screening and regularly supply stool samples according to the study protocol.

• Study Type: Interventional
• Enrollment (Anticipated): 99
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fang Xiao, Doctoral; Phone Number: 008615927368783; Email: christina_fx@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have a diagnosis of ulcerative colitis based on clinical symptoms, as well as laboratory and colonoscopic findings, including histopathologic results of the intestinal mucosa.
2. Ulcerative Colitis complete Mayo score range from 4 to 10 [mild-moderate activity] and Mayo endoscopic score ≥2 as assessed within 4 weeks prior to enrollment and clinical symptoms that are at least stable.
3. Patients failed to acquire clinical remission after full dose and adequate course (4 weeks) of 5-ASA or precursors treatment.
4. Patients ≥ 18 and < 70 years of age are eligible for this trial.
5. All patients must sign a written informed consent document. Assent, when appropriate, will be obtained according to institutional guidelines.

Exclusion Criteria:

1. Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) or other severe immunodeficiency
2. Patients with severe prior allergic reaction to food or supplementary material of placebo will be excluded from the protocol.
3. Patients who are pregnant or lactating will be excluded from the protocol.
4. Suspected as CMV or EBV colitis by endoscopic findings and proved by immunohistochemistry and biopsy PCR.
5. Decompensated life-threatening disease including but not restricted to liver cirrhosis (bleeding varices, ascites, encephalopathy or icterus), heart attack, malignancy and so on.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo capsule arm; Oral administration of 30 placebo capsule containing edible pigmented starch together with full dose of oral 5-Aminosalicylic acid(5-ASA).	Procedure: placebo capsule; Oral administration of 30 placebo capsule containing edible pigmented starch
Active Comparator: SQIMC-md FMT arm; Oral administration of 30 SQIMC-md capsules containing 2*10^13 copies of prepared fecal microbiota lyophilized powder from multiple healthy donors' fresh feces together with full dose of oral 5-Aminosalicylic acid(5-ASA).	Procedure: Standardized Quantitative multi-donor Intestinal Microbiota Capsule (SQIMC-md); heterologous fecal microbiota transplantation (FMT) by Standardized Quantitative multi-donor Intestinal Microbiota Capsule (SQIMC-md)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response rate at week 8 after SQIMC-md treatment.	Assess efficacy of SQIMC-md FMT treatment with the aid of the Mayo score for Ulcerative Colitis clinical disease severity and response rate at week 8 after SQIMC-md treatment. Mayo score (Disease activity index) for Ulcerative Colitis. Total range for complete Mayo score 0-12 (sum from 4 subscales below) and partial Mayo score 0-9 (sum from 1,2 and 4 subscales below): Each subscale for mayo score: Stool frequency: 0-3; Rectal bleeding: 0-3; Mayo endoscopic score: 0-3; Estimation from physician: 0-3 Clinical response rate is defined as a decrease of ≥ 3 points and at least 30% from baseline in the Mayo score, with an accompanying decrease of ≥ 1 point in the subscore for rectal bleeding or an absolute subscore ≤ 1 for rectal bleeding	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	safety of SQIMC-md FMT treatment by recording the incidence of adverse events.	12 weeks
clinical response rate at week4 and week12	Assess the efficacy of SQIMC-md FMT by response rate at week4 and week12	week4 and week12
the remission rate at week12	the remission rate at week12 with the aid of mayo score or partial Mayo score. Clinical remission rate at week 12 after treatment (clinical remission is defined as a Mayo score of ≤ 2 points and no single score > 1 point	12 weeks
Mean (or median) decrease of fecal calprotectin	Assess the efficacy of SQIMC-md FMT measured by the drop of fecal calprotectin.	12 weeks
Mean (or median) change from baseline in Inflammatory Bowel Disease Questionnaire （IBDQ） total score and subscore at week 12	IBDQ includes 32 questions. The questions are grouped into four categories (subscore): Bowel symptoms (B), Systemic symptoms (S), Emotional function (E) and Social function (SF). Response options are consistently presented as seven-point scales (1-7). Total score is defined as the sum of subscore of four categories.	12 weeks

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Investigators: Principal Investigator: Fang Xiao, Doctoral, Tongji Hospital

Publications and helpful links

General Publications

• Huang T, Xu J, Wang M, Pu K, Li L, Zhang H, Liang Y, Sun W, Wang Y. An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis. Medicine (Baltimore). 2022 Jul 29;101(30):e29790. doi: 10.1097/MD.0000000000029790.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 30, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: July 9, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 26, 2019

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Ulcerative colitis; Fecal microbiota transplantation; SQIMC-md
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 2019CR209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to share at least the ICF and CSR after the trial is ended. The data will be available after we finish the trial and the publication. The sharing of the data is planned to lasted for one year.
• IPD Sharing Time Frame: The data will be available after we finish the trial and the publication. The sharing of the data is planned to lasted for one year.
• IPD Sharing Access Criteria: Not decided yet.
• IPD Sharing Supporting Information Type: ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No