Efficacy of Probiotic Against Functional Constipation

Study Overview
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Brief Summary
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This project aims to study the benefits of probiotic in modulating gut microbiota and treating functional constipation in patients aged 18-81.

Detailed Description
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Constipation is a common clinical intestinal functional disease worldwide, and its main manifestations are difficulty in defecation and/or decreased frequency of defecation. Difficulty defecating includes straining, difficulty passing, sensation of incomplete defecation, sensation of anorectal blockage, time-consuming defecation, and need for assistance, fewer bowel movements are fewer than 3 bowel movements per week and the duration of chronic constipation is at least 6 months. The quality of life of patients with chronic constipation is significantly lower than that of non-chronic constipation patients. Some patients have a heavy financial burden due to abuse of laxatives or repeated visits to doctors, including visits to doctors, examinations, direct economic losses caused by treatment and hospitalization and indirect economic losses caused by reduced work productivity and absenteeism. Constipation caused by functional diseases is mainly caused by nerve smooth muscle dysfunction in the colon, rectum and anus, including functional constipation, functional defecation disorder and constipation-predominant irritable bowel syndrome. In some cases, functional constipation may be related to normal or slow colonic transit and/or bowel dysfunction (pelvic floor dysfunction). Constipation treatment methods include basic treatment measures such as increasing dietary fiber and water, increasing exercise and other lifestyles, and establishing good bowel habits. Volumetric laxatives and osmotic laxatives are options for patients with mild to moderate constipation. Stimulant laxatives may be used as a short-term/intermittent remedy. In recent years, the treatment of chronic constipation patients with probiotics has been proposed. Existing research data confirm that patients with chronic constipation have intestinal microecological imbalance. Studies have shown that Bifidobacterium, Lactobacillus, dominant bacterial groups such as Bacteroides decreased significantly, while Escherichia coli, Staphylococcus aureus, Enterobacteriaceae (Citrobacter, Klebsiella, etc.) and fungi and other potential pathogenic bacteria increased significantly, and this trend was related to the severity of constipation. Although probiotics are not the first-line drugs for the treatment of chronic constipation, they can promote intestinal peristalsis and restoration of gastrointestinal motility. Possible mechanisms include changes in the number and types of intestinal flora; metabolites of the flora (methane and short-chain fatty acids), cellular components of bacteria (lipopolysaccharides) or the interaction between bacteria and the host immune system affects a variety of gut functions. Gut microbes through the digestion of polysaccharides in the gut produce short chain fatty acids (short chain fatty acids, SCFAs) to provide energy for the body. SCFAs produced by intestinal flora metabolism also inhibits the growth of pathogenic bacteria and reduces the accumulation of phenolic substances produced by pathogenic bacteria, promote intestinal peristalsis to relieve constipation symptoms.

Official Title
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Efficacy of Probiotic in Patients With Functional Constipation

Conditions
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Constipation - Functional

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the diagnostic criteria for functional constipation in the Rome IV Ruled out for IBS or secondary constipation Exclusion Criteria: Diagnosed with refractory constipation Any other constipation caused by neurological diseases, metabolic diseases, obstructive diseases and drugs Mental illness Immunodeficiency diseases or used immunosuppressants, serious diseases of the heart, brain, kidney and other systems, malignant tumors, intestinal perforation, intestinal obstruction, intestinal bleeding Currently using antibiotics or have a history of taking antibiotics in the past 4 weeks. Participating in other clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>Probiotic Lactobacillus plantarum at 9 log CFU/day for 8 weeks | Dietary Supplement: Probiotic<br>* Probiotic Lactobacillus plantarum at 9 log CFU/day for 8 weeks<br>|
| Placebo Comparator: Placebo<br>Intervention consists of daily administration of 2g of maltodextrin, administered daily for 8-weeks) | Dietary Supplement: Placebo<br>* Intervention consists of daily administration of 2g of maltodextrin, administered daily for 8-weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiota profiles of fecal samples in patients with functional constipation upon administration of probiotic or placebo | Differences in microbiota abundance in fecal sample of patients with functional constipation upon administration of probiotic compared to placebo as assessed via DNA profiling of fecal samples upon Ilumina MiSeq sequencing | 8-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Constipation profiles of patients with functional constipation upon administration of probiotic or placebo | Differences in constipation profiles in patients with functional constipation upon administration of probiotic compared to placebo as assessed via number of complete spontaneous bowel movement (CSBM) per week and bowel habits | 8-weeks | 
| Quality of life profiles of patients with functional constipation upon administration of probiotic or placebo | Differences in QoL profiles in patients with functional constipation upon administration of probiotic compared to placebo as assessed via the Hamilton Anxiety Scale (HAM-A) comprising of 14-items, with a 5-point Likert scale (8-56 points), where a higher score indicates more severe anxiety symptoms | 8-weeks | 
| Defecation profiles of patients with functional constipation upon administration of probiotic or placebo | Differences in defecation profiles in patients with functional constipation upon administration of probiotic compared to placebo as assessed via the balloon expulsion test (time to expel the balloon) | 8-weeks | 
| Defecation profiles of patients with functional constipation upon administration of probiotic or placebo | Differences in defecation profiles in patients with functional constipation upon administration of probiotic compared to placebo as assessed via pelvic floor muscle electromyography | 8-weeks | 
| Immunity profiles of patients with functional constipation upon administration of probiotic as assessed via blood samples | Differences in concentrations of proteins such as interleukins (IL-10, IL-4, IL-6, Tumour Necrosis Factor-alpha, Interferon gamma) in blood samples of patients upon administration of probiotic compared to placebo | 8-weeks |