Efficacy Evaluation of Probiotic Product on Bowel Habits in Healthy Subjects

Study Overview
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Brief Summary
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The objective of this study is to evaluate if consumption of fermented milk containing Lactobacillus casei strain Shirota has an impact on stool consistency, stool frequency, constipation-related symptoms, and quality of life in subjects who frequently have hard or lumpy stools.

Detailed Description
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Constipation is a common problem affecting approximately 17% of the general population in Europe. Several reports suggest that production of hard or lumpy stools (HLS) is strongly associated with the development of constipation. HLS are produced not only by chronic constipated patient but also by healthy population. Thus, reducing the incidence of HLS might be beneficial in terms of reducing the incidence of constipation in healthy population. The results of two clinical studies conducted in Europe indicate the positive effect of fermented milk (FM) containing Lactobacillus casei strain Shirota (LcS) to modulate the hardness or dryness of stools. Koebnick et al. (2003) reported that consumption of the FM drink containing LcS decreased the occurrence of hard or lumpy stools, and improved the severity of constipation in patients with chronic constipation in Germany. An open trial conducted in Ghent, Belgium used commercially available FM containing LcS (Yakult® Light) in subjects who frequently had hard or lumpy stools, screened by an average Bristol Stool Form Scale (BS) score < 3.0. After 3 weeks of treatment, the proportion of subjects who produced hard or lumpy stools (BS score = 1 or 2) ≥ 25% of bowel movements decreased from 73.7% at baseline to 36.8%, while in the non-intervention control group the proportion increased from 75.0% to 85.0% during the same period. Based on the results of those studies, it was anticipated that LcS might assist in reducing the production of hard or lumpy stools in the general population. In order to confirm the efficacy in healthy population, a randomised, double blind, placebo control study is required.

Official Title
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Evaluation of the Impact of a Fermented Milk Containing Lactobacillus Casei Strain Shirota on Stool Consistency, Stool Frequency, Constipation-related Symptoms and Quality of Life in People Who Frequently Have Hard or Lumpy Stools

Conditions
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Constipation

Intervention / Treatment
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* Dietary Supplement: Fermented milk containing Lactobacillus casei strain Shirota
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria; a subject: is informed both verbally and in writing about the objectives of the clinical study, the methods, the anticipated benefits and potential risks and the discomfort to which he/she may be exposed, and give written consent to participate in the study prior to the start of any study-related procedures is healthy female or male, 18-65 years of age, inclusive is conscious of having hard or lumpy stools in daily life has an average Bristol Stool Form Scale score <3.0 per bowel movement female subjects of childbearing potential should use a reliable method of contraception Exclusion Criteria; a subject: is under the age of legal consent is mentally or legally incapacitated is treated by a doctor for her/his constipation has a history of gastrointestinal surgery except for appendectomy has a history of chronic gastrointestinal diseases, including but not limited to inflammatory bowel diseases has a severe gastrointestinal disorder has clinically relevant medical conditions, e.g., renal, hepatic, pulmonary, cardiac, hematological, endocrinological, neurological, or psychiatric conditions is pregnant or wanting to become pregnant during the course of the study is unable to refrain from or anticipates the use of any medication (including laxatives, diuretics, prescription and non-prescription drugs, vitamins and herbal supplements), except for paracetamol, oral contraceptives, or hormonal replacement therapy during the screening visit and for the duration of the study has a history of drug and/or alcohol abuse has milk allergies is intolerant to lactose

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fermented milk<br>Fermented milk containing Lactobacillus casei strain Shirota, 65 ml in a bottle, consume 1 bottle per day. | Dietary Supplement: Fermented milk containing Lactobacillus casei strain Shirota<br>* A fermented milk containing Lactobacillus casei strain Shirota, 65 ml for oral administration, 1 bottle per day for 8 weeks (56 days). One bottle of the drink contains: 42.9 kcal/182 kJ; less than 0.1 g of fat; 9.6 g of carbohydrate; 0.01 g of sodium; 0.9 g of protein; and at least 6.5 x 10^9 colony-forming units of Lactobacillus casei strain Shirota.<br>* Other names: Commercial name: Yakult;|
| Placebo Comparator: Placebo<br>Non-fermented milk without Lactobacillus casei strain Shirota, 65 ml in a bottle, consume 1 bottle per day. | Dietary Supplement: Placebo<br>* Non-fermented milk without Lactobacillus casei strain Shirota, 65 ml for oral administration, 1 bottle per day for 8 weeks (56 days). One bottle of the drink contains: 42.9 kcal/182 kJ; less than 0.1 g of fat; 9.6 g of carbohydrate; 0.01 g of sodium; and 0.9 g of protein.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the proportion of subjects who produce hard or lumpy stools not less than 25%(≥25%) of weekly number of bowel movements | Hard or lumpy stools are defined as stools with Bristol Stool Form Scale score 1 or 2. Incidence of hard or lumpy stools is calculated by weekly basis. | During pre-treatment (2 weeks) and treatment (8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly average Bristol Stool Form Scale score | Bristol Stool Form Scale is a medical aid designed to classify the form of stool with 7 levels; Separate hard lumps like nuts (difficult to pass), score=1; Sausage-shaped but lumpy, score=2;Like a sausage but with cracks on its surface, score=3; Like a sausage or snake, smooth and soft, score=4; Soft blobs with clear-cut edges (passed easily), score=5; Fluffy pieces with ragged edges, a mushy stool, score=6; Watery, no solid pieces, entirely liquid, score=7. | During pre-treatment (2 weeks) and treatment (8 weeks) | 
| Weekly number of spontaneous bowel movements | Spontaneous bowel movement is defined as the bowel movements without laxative use | During pre-treatment (2 weeks) and treatment (8 weeks) | 
| Weekly number of spontaneous complete bowel movements | Spontaneous complete bowel movement is defined as spontaneous bowel movement relieving the feeling of the presence of stool in the distal bowel. | During pre-treatment (2 weeks) and treatment (8 weeks) | 
| Patient Assessment of Constipation Symptoms (PAC-SYM) score | PAC-SYM contains 12 questions which are classified into 3 subdomains (stool symptoms, abdominal symptoms, and rectal symptoms). The average scores of total questionnaires and each subdomain are assessed. | 6 points (Days 1, 15, 29, 43, 57 and 71) | 
| Patient Assessment of Constipation Quality of Life (PAC-QOL) score | PAC-QOL contains 28 questions which are classified into 4 subdomains (physical discomfort, worries and concerns, psychosocial discomfort, and satisfaction). The average scores of total questionnaires and each subdomain are assessed. | 6 points (Days 1, 15, 29, 43, 57 and 71) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hard or lumpy stools, Stool consistency, Stool frequency, Constipation related symptoms, Constipation related quality of life