Efficacy of Bifidobacteria intake on gastrointestinal symptoms in Symptomatic Type 2 diabetes mellitus patients in Abdominis; open-label, Randomized-controlled trial (Binary STAR study)
Efficacy of Bifidobacteria intake on gastrointestinal symptoms in Symptomatic Type 2 diabetes mellitus patients in Abdominis; open-label, Randomized-controlled trial (Binary STAR study)
Fukui Michiaki
University Hospital, Kyoto Prefectural University of Medicine
465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku
+81-75-251-5111
michiaki@koto.kpu-m.ac.jp
Hashimoto Yoshitaka
University Hospital, Kyoto Prefectural University of Medicine
465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku
+81-75-251-5111
y-hashi@koto.kpu-m.ac.jp
Not Recruiting
Dec. 06, 2022
Jan. 19, 2023
100
Interventional
randomized controlled trial
open(masking not used)
no treatment control/standard of care control
parallel 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 do not use new antibiotics within 12 weeks before giving their consent
5. Patients who are not treated with new interventions for diet therapy within 12 weeks before giving their consent
6. Patients who do not change concomitant drugs (addition or withdrawal of the concomitant drugs or change of usage or dose of the concomitant drugs)* that may affect gastrointestinal symptoms or gut microbiota within 12 weeks before giving their consent
*including patients who are using GLP-1 receptor agonists. Patients who need dose titration of the GLP-1 receptor agonists cannot be included in this study. While, patients who are using insulin and need dose titration of the insulin can be included in this study.
7. Male and female aged 20 years or older, and 75 years or younger when giving their consent
8. 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 4 weeks before giving their consent
2. Patients who are diagnosed to have structural diseases* by colonoscopy within 5 years before giving their consent
*Patients with polyps or diverticula that are not considered to affect gastrointestinal function can be included in this study. While, patients with inflammatory diseases (infectious enteritis, diverticulitis, Crohn's disease, ulcerative colitis, etc.) or stenotic lesions, that are likely to affect gastrointestinal function cannot be inclued in this study.
3. Patients with GSRS constipation subdomain score of 3 points or higher, and with Bristol stool form scale of higher than 4 points
4. Patients with GSRS diarrhea subdomain score of 3 points or higher, and with Bristol stool form scale of less than 4 points
5. Patients with both gastrointestinal symptoms of diarrhea and constipation (e.g. patients with mixed-type irritable bowel syndrome)
6. Patients with history or complication of celiac disease or inflammatory bowel disease
7. Patients with HbA1c of 9% or higher at giving their consent
8. Patients who used alpha-glucosidase inhibitor within 4 weeks before giving their consent
9. Patients who are suffered by myocardial infarction, cerebral infarction, or stroke within 12 weeks before giving their consent
10. Patients with severe hepatic dysfunction (AST or ALT is 5 times or more higher than upper limit in the collaborative research institutions
11. Patients with severe renal dysfunction (eGFR is less than 30 ml/min/1.73 square meter)
12. Patients with malignant neoplasm
13. Patients with history of allergy against bifidobacteria
14. Patients who use any other drugs or supplements which affect the functions of the inestines
15. Patients who use drugs which have high possibility to cause gastrointestinal symptoms (prokinetic agents*, gastrointestinal dysfunction the rapeutic agents, antiemetic agents, or anticholinergic agents, etc.)
*Patients who are using PPI or H2blockers can be included in this study, however, initiation or dose change after giving their consent is prohibited.
16. Patients who change their dietary habit within 12 weeks before giving their consent
17. Patients with other conditions that the investigator or researcher thinks inappropriate for the study
20age old over
75age old under
Both
type 2 diabetes mellitus
Group A: administer bifidobacterium-containing antiflatulent for 12 weeks (+/- 3 weeks) as applicable.
Group B: Continue current treatment for 12 weeks (+/- 3 weeks) without administering bifidobacterium-containing antiflatulent
D003924
Change in GSRS total score from baseline to week 12
1. Change and percent change in following parameters from baseline to week 12
- GSRS subdomain scores
- fecal properties / Bristol stool form scale
- defecation frequency
- special blood test biomarkers (total bile acid, Glycoalbumin, 1.5AG, GLP-1, GIP, glucagon)
- general blood test biomarkers (HbA1c, fasting plasma glucose, C-peptide, AST, ALT, GGT, TG, HDL-C, LDL-C, BUN, Cre)
- physical examination (body weight, BMI)
- general urine test biomarker (urinary albumin (creatinine-corrected)
- gut microbiota (type of enterobacteria, relative abundance, alpha diversity, beta diversity)
- macronutrients (carbohydrates, fats, proteins and dietary fiber) measured by BDHQ
2. Proportion of subjects whose fecal property (Bristol stool form scale) is within normal range (3.5-4.5)
3. Medication adherence of the study agent
4. Factors that affect GSRS total score or constipation/diarrhea subdomain scores
5. Following items stratified by baseline symptoms (constipation/diarrhea)
- GSRS total score
- GSRS subdomain scores
- Proportion of subjects whose fecal property (Bristol stool form scale) is within normal range (3.5-4.5)
- defecation frequency
- blood test biomarkers (HbA1c, fasting blood glucose, C-peptide, total bile acid, Glycoalbumin, 1.5AG)
- gut microbiota (type of enterobacteria, relative abundance, alpha diversity, beta diversity)
Biofermin Seiyaku Co., Ltd.
Not applicable
Kyoto Prefectural University of Medicine, Clinical Research Review Board
