Clinical trial NCT04982380: Efficacy and Safety of Bifidobacterium Quadruple Live Tablets in Patients With T2DM and Constipation
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus With Complication
Keywords: Type 2 diabetes;Constipation;Gut microbiota;Bifidobacterium
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Harbin Medical University
name: The Affiliated Hospital of Inner Mongolia Medical University
name: Affiliated Hospital of Chengde Medical University
name: The First Affiliated Hospital of Zhengzhou University
name: Chinese Academy of Sciences
name: Hangzhou Grand Biologic Pharmaceutical, Inc.
First posted: 2021-07-29
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of bowel movements
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
measure: Glycosylated hemoglobin
timeFrame: Baseline, Week 12, Week 16
measure: Glycosylated albumin
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Secondary outcomes:
measure: Gut micobiota
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: The ratio of CSBMs to SBMs
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
measure: Bristol Stool Scale
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
measure: Bowel Function Index (BFI)
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
measure: Patient Assessment of Constipation symptom (PAC-SYM)
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
measure: Patient global impression of changes (PGIC)
timeFrame: Week 16
measure: The first time of CSBM
timeFrame: Week 1 to Week 16
measure: Fasting blood glucose
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
measure: Serum lipid spectrum
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Weigang Zhao, MD
role: PRINCIPAL_INVESTIGATOR
References: