Efficacy and Safety of Bifidobacterium Quadruple Live Tablets in Patients With T2DM and Constipation

Efficacy and Safety of Combined Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus Tablets, Live (Siliankang) in Patients With Type 2 Diabetes and Constipation: a Randomized, Double-blind, Placebo-controlled, Multicenter Trial

Constipation is one of the common complication of diabetes mellitus, whose pathogenesis was previously recognized as decreased gastrointestinal motility caused by diabetic autonomic neuropathy. It is always treated with gastrointestinal motility drugs or laxatives which may have side effects such as gut microbiota dysbiosis and withdraw symptoms. Recently, researches have indicated that the risk of developing type 2 diabetes mellitus is associated with alterations in the structure of the gut microbiota and have begun to treat diabetic constipation by improving gut microbiota of these patients. The rational use of microecological preparation for the prevention and treatment of diabetic constipation has received increasing attention. This trial is aimed to evaluate the efficacy and safety of Combined Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus Tablets, Live (Siliankang) in the treatment of patients with type 2 diabetes and constipation, and to analyze its influence on gut microbiota and blood glucose.

Study Overview

• Status: Not yet recruiting
• Conditions: Type 2 Diabetes Mellitus With Complication
• Intervention / Treatment: Drug: Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus Tablets, Live; Drug: Siliankang simulating tablets

Detailed Description

This is a 16 week, 1:1 randomised, controlled, open label, two-arm, parallel-group trial evaluating efficacy and safety of Combined Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus Tablets, Live (Siliankang) in patients with type 2 diabetes and constipation. Patients will be randomized into experimental group or control group treated with Siliankang or placebo tablets respectively. Total trial duration for the individual subject will be approximately 16 weeks including screening, 12-weeks treatment and 4-weeks follow-up. Patients will attend at 2-week, 8-week, 12-week and 16-week throughout the trial taking physical examination, having blood test, collecting faecal specimen and completing the questionnaire of constipation under the direction of doctors.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• According to the diagnostic criteria of World Health Organization (WHO) in 1999, type 2 diabetes mellitus was diagnosed clinically. The duration of T2DM was no more than 8 years (including 8 years).
• According to the ROME III diagnostic criteria of functional constipation or guideline for diagnosis and treatment of chronic constipation in China (2013 edition), chronic constipation was diagnosed clinically. The duration of constipation was more than 6 months (including 6 months).
• The age ranged from 18 to 70 years (including 18 and 70 years) with no restriction of sex.
• Fasting blood glucose was no more than 8mmol/L and glycosylated hemoglobin ranged from 7.0% to 10.0% (including 7.0% and 10.0%).
• Sign written consent form voluntarily.

Exclusion Criteria:

• Other types of diabetes mellitus.
• History of diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome.
• Constipation induced by drugs[i.e. antidepressants, calcium antagonists, diuretics, sympathetic agents, antacids with aluminum or calcium, calcium agents, iron agents, antidiarrhetics].
• Organic constipation [i.e. intestinal diseases，endocrine and metabolic diseases (except diabetes), nervous system and muscle disease].
• Gastrointestinal diseases [i.e. colitis, mesenteric lymphadenitis, with a history of intestinal surgery].
• Using drugs that may affect clinical outcome evaluation in the past 2 weeks, such as antibiotics (penicillin, amoxicillin, erythromycin, azithromycin and cephalosporin, etc.), microecological preparations, laxative drugs (magnesium sulfate and lactulose, etc.); anthraquinones (rhubarb, aloe and senna, etc.); Gastrointestinal motility drugs (metoclopramide, domperidone, cisapride, etc).
• History of myocardial infarction or stroke within 6 months, or existing severe cardiovascular disease and risk.
• Abnormal liver function [i.e. serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is 1.5 times higher than the upper limit of normal value]. Abnormal renal function [Creatinine exceeds the upper limit of normal value].
• Severe hypertension that defined as systolic blood pressure ≥160 mmHg, diastolic blood pressure ≥90 mmHg with drug therapy, or hypotension (resting seat blood pressure < 90/50 mmHg).
• History of acute and chronic gastroenteritis or gastrointestinal surgery
• Psychosis, alcohol dependence or history of drug abuse.
• Lactating women, pregnant women and patients who have pregnancy plan during the trial or within 3 months after the trial.
• Participation in other studies three months before the trial.
• Allergic constitution or allergic to a variety of drugs.
• Those researchers think inappropriate to the research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group; Patients will be instructed to continue current antidiabetic treatment, which should be kept unchanged throughout the trial, and start treatment with Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus Tablets, Live (Siliankang) 3 tablets p.o. tid for 12 weeks.	Drug: Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus Tablets, Live; Patients will be instructed to continue current antidiabetic treatment, which should be kept unchanged throughout the trial, and start treatment with Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus Tablets, Live (Siliankang) 3 tablets p.o. tid for 12 weeks.; Other Names: Siliankang
PLACEBO_COMPARATOR: Control group; Patients will be instructed to continue current antidiabetic treatment, which should be kept unchanged throughout the trial, and start treatment with Siliankang simulative tablets 3 tablets p.o. tid for 12 weeks.	Drug: Siliankang simulating tablets; Patients will be instructed to continue current antidiabetic treatment, which should be kept unchanged throughout the trial, and start treatment with Siliankang simulative tablets 3 tablets p.o. tid for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of bowel movements	Changes from baseline in the number of completely spontaneous bowel movements (CSBMs) and number of spontaneous bowel movements (SBMs). Effectiveness is defined as CSBMs more than 3 times weekly (including 3 times) with increase from baseline, while ineffectiveness is defined as CSBMs less than 3 times weekly or with no increase from baseline.	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Glycosylated hemoglobin	Changes from baseline in glycosylated hemoglobin.	Baseline, Week 12, Week 16
Glycosylated albumin	Changes from baseline in glycosylated albumin.	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut micobiota	Changes from baseline in gut microbiota.	Baseline, Week 4, Week 8, Week 12, Week 16
The ratio of CSBMs to SBMs	Changes from baseline in the ratio of CSBMs to SBMs.	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Bristol Stool Scale	Proportions whose stool characters recover to Type III and IV by Bristol Stool Scale.	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Bowel Function Index (BFI)	Changes from baseline in the score of Bowel Function Index (BFI).	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Patient Assessment of Constipation symptom (PAC-SYM)	Changes from baseline in the scale of Patient Assessment of Constipation symptom (PAC-SYM).	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Patient global impression of changes (PGIC)	Difference in the Patient global impression of changes (PGIC) between experimental group and control group.	Week 16
The first time of CSBM	Difference in the first time of completely spontaneous bowel movement (CSBM) between the experimental group and control group.	Week 1 to Week 16
Fasting blood glucose	Changes from baseline in fasting blood glucose.	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Serum lipid spectrum	Changes from baseline in serum lipid spectrum.	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Chinese Academy of Sciences; The First Affiliated Hospital of Zhengzhou University; The Affiliated Hospital of Inner Mongolia Medical University; First Affiliated Hospital of Harbin Medical University; Affiliated Hospital of Chengde Medical University; Hangzhou Grand Biologic Pharmaceutical, Inc.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 31, 2021
• Primary Completion (ANTICIPATED): July 31, 2022
• Study Completion (ANTICIPATED): July 31, 2022

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: July 23, 2021
• First Posted (ACTUAL): July 29, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 29, 2021
• Last Update Submitted That Met QC Criteria: July 23, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Type 2 diabetes;Constipation;Gut microbiota;Bifidobacterium
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Signs and Symptoms, Digestive; Diabetes Mellitus; Diabetes Mellitus, Type 2; Constipation; Diabetes Complications
• Other Study ID Numbers: SLK-HS2843

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No