臨床研究等提出・公開システム

Effect of probiotics, Bifidobacteria, on Gastrointestinal Symptoms in Patients with Type 2 diabetes mellitus; open-label, single-Arm, exploratory Research

Big STAR study

40

[Age (year (SD))] 64.0 (9.4) [Sex (male / female)] 26/14 [Duration of diabetes (year (SD))] 11.8 (8.2) [height (cm (SD))] 163.5 (8.7) [body weight (kg (SD))] 67.6 (12.7) [BMI (kg/m2 (SD))] 25.0 (3.9)

December 24, 2019: Protocol approved by certified review board February 19, 2020: Publication at jRCT (Start of this study) April 8, 2020: First Subject In August 19, 2020: Last Subject In November 27, 2020: Last Subject Last Visit

[Death (n)] 0 [Adverse event (n)] 4 [Serious adverse event (n)] 0 [Disease or the like (n)] 0 [Serious disease or the like (n)] 0

- The primary endpoint of this study, change in GSRS total score, significantly improved from baseline to week 10. - All subdomain scores of GSRS significantly improved from baseline to week 10. - Subdomain score related to diarrhea and constipation also significantly improved from baseline to week 12, after 2 weeks of study drug discontinuation. - Bristol scale score did not significantly improve from baseline to week 10. - Operational Taxonomic Unit of enteric bacteria (estimated number of bacterial species), Faith's Phylogenetic Diversity, Chao1 (abundance of bacterial species) did not significantly change from baseline to week 10. - p_Firmicute significantly increased from baseline to week 10, and p_Bacteroidetes significantly decreased from baseline to week 10. - g_Sutterella significantly decreased from baseline to week 10. - HbA1c significantly improved from baseline to week 10 only in female. - Change in HbA1c and plasma glucose from baseline to week 10 tended to be correlated with change in GSRS from baseline to week 10. - No serious or specific adverse event occurred during this study.

Biofermin tablet significantly improved total score and all subdomain scores of GSRS, and the improvement of subdomain score related to diarrhea and constipation continued to week 12, after 2 weeks of study drug discontinuation.g_Sutterella significantly decreased, suggesting the continuous effect of biofermin tablet on gut microbiota, even after the drug discontinuation. HbA1c did not worsened, or even improved in female. Improvement of abdominal symptom may contribute to better glycemic control.

June. 30, 2022

No

N/A

https://jrct.mhlw.go.jp/latest-detail/jRCTs051190109

Fukui Michiaki

University Hospital, Kyoto Prefectural University of Medicine

Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

michiaki@koto.kpu-m.ac.jp

Hashimoto Yoshitaka

University Hospital, Kyoto Prefectural University of Medicine

Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

+81-75-251-5111

y-hashi@koto.kpu-m.ac.jp

Complete

Feb. 19, 2020

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Patients who meet all of the following criteria are included in this study:
1. Patients with gastrointestinal symptoms such as diarrhea or constipation
2. Patients whose mean Gastrointestinal Symptom Rating Scale (GSRS) subdomain score (diarrhea, constipation) is three or higher
3. Patients who are diagnosed with type 2 diabetes mellitus without neuropathy
4. Patients who use metformin and who do not use four or more antidiabetic agents
5. Patients who do not use new antibiotics within 12 weeks before giving their consent
6. Patients who are not treated with new interventions for diet therapy within 12 weeks before giving their consent
7. Patients who do not change concomitant drugs (addition or withdrawal of the concomitant drugs or change of usage or dose of the concomitant drugs) within 12 weeks before giving their consent
8. Male and female aged 20 years or older, and 75 years or younger when giving their consent
9. Patients who give their consent in a written form

Patients who fall into any of the following criteria are excluded from participating in the study:
1. Patients whose mean weekly defecation is less than once, or 42 times or more within 1 month before giving their consent
2. Patients who are diagnosed to have structural diseases by colonoscopy within 5 years before giving their consent
3. Patients with history or combination of celiac disease or inflammatory bowel disease
4. Patients with HbA1c of 9% or higher at giving their consent
5. Patients who are suffered by myocardial infarction, cerebral infarction, or stroke within 12 weeks before giving their consent
6. Patients with severe hepatic dysfunction (AST or ALT is 5 times or more higher than upper limit in the collaborative research institutions
7. Patients with severe renal dysfunction (eGFR is less than 30 ml/min/1.73 square meter)
8. Patients with malignant neoplasm
9. Patients with history of allergy against bifidobacteria
10. Patients who use any other drugs or supplements which affect the functions of the inestines
11. Patients who use GLP-1 receptor antagonists or drugs which have high possibility to cause gastrointestinal symptoms (prokinetic agents, gastrointestinal dysfunction therapeutic agents, antiemetic agents, or anticholinergic agents, etc.)
12. Patients who routinely take foods, supplements or pharmaceutical agents including bifidobacteria (such as yogurt or chocolates)
13. Patients with other conditions that the investigator or researcher thinks inappropriate for the study

Both

gastrointestinal symptoms

Study subjects take the study agent for 10 weeks (plus/minus 2 weeks)

Change in GSRS score from baseline to week 10

1. Change and percent change in following parameters from baseline to week 12
- GSRS score
- fecal properties / Bristol Scale score
- HbA1c
- Glycoalbumin
- fasting plasma glucose
- C-peptide
- active GLP-1
- total bile acid
- gut microbiota (type of enterobacteria, relative abundance, alpha diversity, and beta diversity)
2. Change in GSRS score from baseline to week 10 stratified by following factors
- age
- gender
- BMI
- type of gastrointestinal symptoms
- administrating drugs
3. Correlations between change in fecal properties and change in biomarkers above

+81-75-251-5337

Dec. 24, 2019

none