臨床研究等提出・公開システム

Single center randomized study: Alginate combined fecal microbiota transplantation for ulcerative colitis

Alginate combined fecal microbiota transplantation for ulcerative colitis

53

Recently, the efficacy and safety of fecal transplantation therapy for ulcerative colitis (UC) have been reported in adults, and it has also begun to be reported in pediatric patients, making it highly necessary to introduce this therapy as an option in the treatment of refractory cases. Aiming at more effective reconstruction of the intestinal microbiota and enhancement of the efficacy of stool transplantation therapy, our research group proposed "antimicrobial combination stool transplantation therapy (A-FMT therapy)" in which three antimicrobial agents (AFM: amoxicillin, fosfomycin, and metronidazole) are administered as pretreatment before stool transplantation, and started clinical The studies "Investigation of the efficacy of fecal transplantation therapy combined with antibiotic therapy for ulcerative colitis (UMIN ID: 000014152)", "Investigation of the efficacy of fecal transplantation therapy and antibacterial therapy for patients with ulcerative colitis (UMIN ID: 000018642)" and "Analysis of factors related to the efficacy of fecal transplantation therapy for patients with ulcerative colitis (UMIN ID: 000018642)" were conducted in July 2014. (UMIN ID: 000018642) and "Analysis of Factors Related to the Efficacy of Stool Transplant Therapy for Ulcerative Colitis Patients" (Juntendo Medical School Ethics Committee Reception Number: 16-169). In addition, data from the Faculty of Pharmaceutical Sciences of Keio University, a collaborating institution, found that alginic acid, a non-digestible polysaccharide derived from seaweed, hastens recovery from intestinal inflammation by increasing intestinal bacteria and their metabolites that promote the regeneration of colon epithelial cells. In this study, we will explore these studies to determine the alginate-additive effect of antimicrobial combination stool transplant therapy for ulcerative colitis and its factors. Fifty-three patients (37 males and 16 females, mean age 38.5 years) and 19 donors (8 males and 11 females, mean age 34.6 years) participated in the study.

From September 1, 2020 to September 30, 2022, 53 patients and 19 donors were enrolled. The initial target number of patients was 60, but the number of cases could not be increased due to the spread of coronavirus infection. Of the 53 patients enrolled, one patient was excluded before randomization, four patients dropped out after randomization, and 48 patients completed the study (23 in the placebo group and 25 in the alginate group).

No serious illnesses were observed in this study, and we believe it was a safe therapeutic intervention.

In this study, the change from baseline in Total Mayo Score at 8 weeks of intake of the test food was the primary endpoint, with a change of minus 3.3 plus or minus 2.3 (p < 0.0001) for the placebo group and minus 3.2 plus or minus 3.2 (p < 0.0001) for the alginic acid group. Comparisons between groups did not reach significance (p = 0.93).

Patients 20 years of age or older with active UC with a Total Mayo score of 3 to 10 points and a Sum Endoscopic Mayo Score of 2 or more points were included in the clinical trial. Relatives or other volunteer donors aged 20 years or older were selected after rigorous screening. After 2 weeks of oral administration of three antimicrobial agents, frozen stools of the donors were dissolved in saline solution and approximately 200 ml of the donors' stools were dissolved and spread by colonoscopy. For the next 8

July. 16, 2024

Yes

undecided

https://jrct.mhlw.go.jp/latest-detail/jRCTs031200103

Ishikawa Dai

Juntendo University Hospital

3-1-3 Hongo,Bunkyo-ku,Tokyo

dai@juntendo.ac.jp

Nomura Kei

Juntendo University Hospital

3-1-3 Hongo,Bunkyo-ku,Tokyo

+81-3-3813-3111

ke-nomura@juntendo.ac.jp

Complete

Sept. 01, 2020

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

Patients
1.Eligible patients are active UC with a total Mayo score 15 of 3 to 10 points and a sum endoscopic mayo score of >=2.And they had exclusion diagnosis of infectious enterocolitis is done.
2.Ages 20 and over
3.Both gender
4.Hospitalized patients or outpatients.
5.Written and oral informed consent with a sufficient understanding.

Stool Donors
1.Healthy persons
2.20 year older
3.Both gender
4.A doctor interviews the donor candidate about the health condition, the past medical history, the life history, and the candidate answers correctly (those who refuse to answer are not allowed to participate)
5.The donor who the doctor judged that there is no problem in health condition will take the following examinations.
1)Fecal examination: The toxin (C. difficile toxin) and the pathogenic bacteria and parasites (general fecal culture, microscopic parasite egg inspection).
2) Blood test: hepatitis A, hepatitis B, hepatitis C, H IV antibody, HTLV antibody, syphilis (RPR / TP), cytomegalovirus antibody, ameba antibody, tuberculosis.
3) Saliva test: SARS-CoV-2 antigen.
4) Mental symptoms

The choice of donor will be made according to the needs of the patient. If a patient wishes a donor known by the investigator, the patient and the donor candidate will be present in front of the doctor confirming their will and sign the consent forms.

Patients
1.Patients using local therapy.
2.All cases with liver disease, kidney disease, heart disease and other serious complications, judged inappropriate by the attending doctor.
3.Cases with complications of other autoimmune diseases.
4.Nursing women, pregnant women and all cases with the possibility of pregnancy.
5.Patients with allergic diseases
6.Other cases judged inappropriate by the principal investigator.
7.Patients who were treated with antibiotics within three month

Stool Donors
1.Those from whom the informed consent is not obtained.
2.Cases suspected of the infectious diseases in inquiries, blood test and fecal examination screening or having a past disease to be excluded.
Excluded disease:
Inflammatory bowel disease, irritable bowel syndrome, chronic diarrhea, severe constipation, colonic polyps, colon cancer, autoimmune diseases, atopic dermatitis, severe obesity, chronic fatigue syndrome.
3.Other cases judged inappropriate by the principal investigator.
4.Donors who were treated with antibiotics within three month.
5.Donors who have a BMI of 30 or higher.

Both

Ulcerative colitis

A-FMT plus algin acid therapy arm
Patients are performed Colonoscopy before participating in this clinical research and make sure the patients is eligible. Patient undergoes FMT two days after AFM therapy. Approximately 150 g to 200 g of fresh stool provided in advance from a donor is dissolved in 500 ml of physiological saline, and the treated stool that has been processed to remove excess residues and the like through a filter is stored frozen at minus 80 degree celsius. The diluted and filtered fecal suspension with dextrin added is transferred into the patients colon from cecum to rectum during total colonoscopy. As usual examinations, the patient undergoes biopsy of inflammatory site. For the next 8weeks, patients take algin acid two times a day every single day.

A-FMT plus placebo arm
Patients are performed Colonoscopy before participating in this clinical research and make sure the patients is eligible. Patient undergoes FMT two days after AFM therapy. Approximately 150 g to 200 g of fresh stool provided in advance from a donor is dissolved in 500 ml of physiological saline, and the treated stool that has been processed to remove excess residues and the like through a filter is stored frozen at minus 80 degree celsius. The diluted and filtered fecal suspension with dextrin added is transferred into the patients colon from cecum to rectum during total colonoscopy. As usual examinations, the patient undergoes biopsy of inflammatory site. For the next 8weeks, patients take Placebo two times a day every single day.

Ulcerative colitis

Antibiotics FMT algin acid

Change of Total Mayo Score at the point of 8 weeks from baseline

1.Change of Sum Endoscopic Mayo Score at the point of 8 weeks from baseline
2.Change of metagenome at the point of 8 weeks from baseline

+81-3-5802-1584

Aug. 25, 2020

none