Efficacy of probiotics (Biofermin) in patients with Renal dysfunction (Diabetic kidney disease) complicated with constipation; an Exploratory, multicenter, open-label, single-arm before-after study

JRCT ID: jRCTs031220479

Registered date:29/11/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: type 2 diabetes mellitus, constipation
• Date of first enrollment: 29/06/2023
• Target sample size: 30
• Study type: Interventional
• Intervention(s): Administer biofermin tablet orally for 12 weeks (six tablests per day, divided to three times per day, in general)

Outcome(s)

• Primary Outcome: Proportion of patients with normal fecal condition (mean of Bristol Scale within 2 weeks before week 12 is 3.5 or higher, and less than 4.5)

Secondary Outcome

Change in the following items from baseline to week 12;
- fecal condition (Bristol Scale)
- defecation frequency
- GSRS (Gastrointestinal symptom rating scale) score
- DTSQ (Diabetes treatment satisfaction questionnaire) score
- BDHQ (Brief-type self-administered Diet History Questionnaire) score
- special stoll tests (intestinal microflora (16S), organic acids in stool: formic acid, acetic acid, propionic acid, butyric acid, valeric acid, lactic acid, succinic acid)
- special blood tests #1 (blood urine toxin, phenyl sulfate, indoxyl sulfate, p-cresyl sulfate, trimethylamine-N-oxide)
- special blood tests #2 (LPS-binding protein, glycoalbumin)
- general blood tests
- abdominal symptoms (heaviness, residual stools, abdominal fullness, abdominal discomfort)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

<inclusion criteria at provisional enrollment>
1. patients with type 2 diabetes mellitus
2. patients with HbA1c of 6.5% or higher, and less than 9.0% at giving their consent
3. patients with constipation symptoms
4. patients with stage 2 to 4 diabetic nephropathy
5. patients aged 18 years or older, and 75 years or younger at giving their consent
6. patients who give their consent in a written form

<Inclusion criteria at actual enrollment>
1. patients with fecal condition (mean of Bristol Scale within 2 weeks before visit 1 (baseline (week 0))) of less than 3.5
2. patients who privide their fecal samples at visit 1 (baseline (week 0))

Exclude criteria

<Exclusion criteria at provisional enrollment>
1. patients who had myocardial infarction, cerebral infarction, or stroke within 12 weeks before giving their consent
2. patients with severe hepatic dysfunction (AST or ALT > 5 times the upper limit of the reference value of the participating medical institution)
3. patients with stage 5 diabetic nephropathy or on dialysis
4. patients with malignant neoplasms*
*Patients who have a history of malignant neoplasms but who have been already cured can be enrolled. However, patients with a hisotory of or with current malignant neoplasms in stomach, small intestine, or large intestine are exclued.
5. patients with history of allergy to bifidobacteria
6. patients who have been consuming foods or supplements such as yogurt or chocolate containing bifidobacteria on a daily basis within 4 weeks before giving their consent. Daily intake is defined as intake at least once a day.
7. patients who have received new antibiotics within 12 weeks before giving their consent
8. patients who have received intestinal regulator (except constipation reliever) within 12 weeks before giving their consent
9. patients who have received a new dietary intervention within 12 weeks before giving their consent
10. patients who have changed (added, discontinued, or changed the dose of) medications that may influence bowel or gastrointestinal function, or antidiabetic agents* that may influence glyemic control within 12 weeks before giving their consent
*Patients who titratted insulin injection can be enrolled. However, patients who titrated combination injection of insulin and GLP-1 receptor agnosist are excluded.
11. patients with other conditions that the investigators judge to be inappropriate for the study

<Exclusion criteria at actual enrollment>
1. patients who took foods or supplements such as yogurt or chocolate containing bifidobacteria on a daily basis for 4 weeks after giving their consent until the actual enrollment. Daily intake is defined as intake at least once a day.
2. patients who received antibiotics after giving their consent until the actual enrollment
3. patients who received dietary intervention after giving their consent until the actual enrollment
4. patients who have changed (added, discontinued, or changed the dose of) any medication after giving their consent until the actual enrollment
5. patients who have received intestinal regulator (except constipation reliever) after giving their consent until the actual enrollment
6. patients who had myocardial infarction, cerebral infarction, or stroke after giving their consent until the actual enrollment
7. patients with other conditions that the investigators judge to be inappropriate for the study

Related Information

• Primary Sponsor: Hirotaka Watada
• Source(s) of Monetary Support: Biofermin Seiyaku Co., Ltd.