A-FMT for active UC

JRCT ID: jRCTs031220542

Registered date:01/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Mild to moderate ulcerative colitis
• Date of first enrollment: 27/03/2023
• Target sample size: 37
• Study type: Interventional

Intervention(s)

1. Amoxicillin hydrate 1,500 mg, fosfomycin calcium hydrate 3,000 mg, and metronidazole 750 mg orally in divided doses 3 times/day, respectively, for 2 weeks.
2. 2-7 days after completion of antimicrobial administration, FMT is performed (200 mL of intestinal microbiome solution) by colonoscopy. 1 and 2 weeks after first FMT, FMT will be performed (100 mL of intestinal microbiome solution) by enema.

Outcome(s)

Primary Outcome

The primary outcome is the clinical remission rate at 8 weeks after the start of FMT treatment.
Clinical remission is defined by the Modified Mayo Disease Activity Index (MMDAI) as followings.
1) Stool frequency subscore = 0 or a decrease of at least 1 point from the stool frequency subscore at the time of eligibility confirmation (average of MMDAI stool frequency subscores for the 3 days prior to the eligibility confirmation date)
2) Blood stool subscore = 0
3) Endoscopic subscore <= 1

Secondary Outcome

1) Changes in each subscore of MMDAI (at the time of eligibility confirmation, 8 weeks after the start of FMT treatment)
2) Changes in each subscore of Mayo Score (at the time of eligibility confirmation, 8 weeks after the start of FMT treatment)

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Inclusion criteria for patients
1) Patients with active left-sided ulcerative colitis or pancolitis.
2) Inadequate response or intolerance to 5-ASA.
3) Patients with a mean stool frequency MMDAI subscore of 0-2 in the last 3 days prior to the date of eligibility confirmation
4) Patients with a mean blood stool MMDAI subscore of 1-2 and a subscore of 1 point or higher in the last 3 days prior to the date of eligibility confirmation
5) Patients with MMDAI endoscopic subscore of 2 points evaluated by colonoscopy performed between 2 weeks prior to the eligibility confirmation date and the eligibility confirmation date
6) Patients diagnosed with ulcerative colitis for more than 12 weeks prior to the eligibility confirmation date
7) Age 16 years or older at the time of obtaining informed consent
8) Outpatients / Inpatients: Outpatients only
9) Patients who can obtain written consent of the research participation by free will. If the patient is under 18 years of age at the time of consent, he/she must be able to obtain a written consent from his/her legal guardian or representative.

Inclusion criteria for donors
1) Healthy persons who are 18 years of age or older at the time of obtaining consent.
2) Persons who can donate stool regularly.
3) Persons who can undergo a medical interview and screening tests (blood test, stool test, and saliva test) on a regular basis
4) Persons who have the capacity to consent and can obtain written consent of their own free will.

Exclude criteria

Exclusion criteria for patients
1) Patients with severe allergies to the drugs used in this study
2) Patients who have received any of the following medications or procedures within the time period specified below
(1) 5-ASA preparations in excess of the prescribed dose : 4 weeks prior to the date of eligibility confirmation
(2) Steroids (oral, rectal, suppository, hemorrhoid treatment, inhalation, injection): 4 weeks prior to the date of eligibility confirmation
(3) Cytapheresis: 4 weeks prior to date of eligibility confirmation
(4) Immunomodulators (cyclosporine, tacrolimus, methotrexate, azathioprine, 6-mercaptopurine): 4 weeks prior to the date of eligibility confirmation
(5) Biologics: 12 weeks prior to the date of eligibility confirmation
(6) Antibiotics for the treatment of ulcerative colitis: 3 months prior to the date of eligibility confirmation
(7) Antidiarrheal drugs: 2 weeks prior to the date of eligibility confirmation
(8) Antidiarrheal treatment for IBS-D: 2 weeks prior to the date of eligibility confirmation
(9) Intestinal cleansing agents (except for use as a pretreatment for colonoscopy for this study): 2 weeks prior to the date of eligibility confirmation
(10) Laxatives (except for use in the pretreatment of colonoscopy for this study): 2 weeks prior to the date of eligibility confirmation
(11) Enema (except for use as a pre-treatment for colonoscopy for this study): 2 weeks prior to the date of eligibility confirmation
(12) Live vaccines: 4 weeks prior to the date of eligibility confirmation
(13) Probiotics: 1 week prior to the date of eligibility confirmation
3) Patients who have changed the dosage of the following drug therapies within the time period indicated below (if the route of administration is the same, a change in drug form is acceptable)
(1) 5-ASA (oral): 4 weeks prior to the date of eligibility confirmation
4) Patients with a history of colorectal resection or patients scheduled for surgical treatment of the gastrointestinal tract during the study period
5) Patients who are clinically suspected of having infectious enteritis
6) Patients with tuberculous disease
7) Patients with liver cirrhosis (e.g., end-stage primary biliary cirrhosis) with signs of portal hypertension
8) Patients with infections and deep-seated fungal infections for which there are no effective antimicrobial agents
9) Patients with severe cardiac disease
10) Patients with renal impairment (serum creatinine of 2.0 mg/dL or higher, or BUN of 25 mg/dL or higher)
11) Patients with hepatic impairment (total bilirubin of 3.0 mg/dL or higher, or AST (GOT) or ALT (GPT)* of 100 IU/L or higher)
12) Patients with malignant tumors or patients who have not been treated for 5 years
13) Patients with obvious psychiatric symptoms (equivalent to Grade 2 or higher in "Criteria for Classification of Severity of Adverse Reactions to Drugs" (June 29, 1992, Drug Proposal No. 80), regardless of treatment)
14) Patients with a history of drug addict or alcohol addiction
15) Pregnant women, lactating women, women who may be pregnant, women who wish to become pregnant from the time of obtaining consent through the duration of treatment, and women who cannot agree to use an appropriate method of contraception (intrauterine devices, pessaries, or compliance with partner condom use; however, oral contraceptives are prohibited)
16) Patients who are participating in other clinical studies or trials, including follow-up studies, at the time of obtaining consent
17) Patients who have been administered other investigational drugs within 12 weeks prior to this study
18) Other patients who are regarded inappropriate by the attending doctor.

Exclusion criteria for donors
1) Persons suspected of having health problems or risks based on health status, medical history, treatment history, vaccination history, high-risk behaviors (piercing, needle sticking, unspecified sexual contact), and travel history.
2) Persons suspected of being infected with the following pathogenic viruses, bacteria, or parasites.
Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Hepatitis E virus, HIV-1/2, HTLV-1, Cytomegalovirus, EB virus, Syphilis, Mycobacterium tuberculosis, Clostridioides difficile, Enterohemorrhagic E. coli (O-157), Enteroaggregative E. coli (EAEC), Enteropathogenic E. coli (EPEC), Enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC), Enteroinvasive E. coli (EIEC), Salmonella, Shigella, Yersinia, Campylobacter, Vibrio parahaemolyticus, Vibrio cholerae, Vibrio vulnificus, Plesiomonas shigelloides, Drug-resistant bacteria, Adenovirus, Norovirus, Rotavirus, Astrovirus, Sapovirus, SARS-CoV-2, Parasites (Strongyloides stercoralis, Giardia, Cryptosporidium, Entamoeba histolytica, Cyclospora, other worm eggs and worms).
3) Deviations from reference values for the following blood tests.
General peripheral blood tests, Creatinine, C-reactive protein, AST, ALT, ALP, Total bilirubin, Albumin.
4) Persons whose fecal hemoglobin test results are positive for fecal occult blood<For women, the test is performed outside the menstrual period>.
5) Persons who are judged to be inappropriate by the doctor.

Related Information

• Primary Sponsor: Nagahara Akihito
• Source(s) of Monetary Support: Metagen Therapeutics, Inc.