Effect of Probiotic Formula on Reducing the Risk for Antibiotic-associated Diarrhoea

Study Overview
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Brief Summary
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Antibiotic treatment disturbs the balance of the intestinal microbiota and predisposes to antibiotic associated diarrhea. Previous studies have shown that the risk of developing diarrhea during a course of antibiotics may be reduced by simultaneous consumption of probiotics. The aim of the present study is to assess the effect of a probiotic formula containing four strains on reducing the risk of antibiotic associated diarrhea.

Detailed Description
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The aim of the study is to assess the effect of a probiotic formula on reducing the risk of antibiotic-associated diarrhea (AAD). The study will be conducted as a two-arm, parallel groups, placebo-controlled, double-blind, randomized clinical trial, stratified by age, gender and number of days on antibiotics. The duration of patient participation in the study will be up to 7 weeks (up to 3 weeks supplementation, 4 weeks follow-up). The overall duration of the study is expected to be approximately 8 months. Adult males and females that are prescribed antibiotic therapy for minimum of 3 and a maximum of 14 days will be included in the study. The incidence of AAD will be evaluated as the primary end-point. The stool from patients presenting diarrhea will be tested for the presence of Clostridium difficile and if negative for C. difficile, also for the presence of other common pathogens causing diarrhea. The overall microbiota will be analyzed from fecal samples taken regularly during each phase of the study.

Official Title
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Effect of Probiotic Formula on Reducing the Risk for Antibiotic-associated Diarrhoea

Conditions
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Antibiotic-associated Diarrhoea

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: Males and females aged 18-65 years. Patients will be initiating antibiotic therapy. The antibiotic therapy consists of one of the following: broad spectrum penicillins, cephalosporins, doxycycline, clarithromycin, ciprofloxacin or isoxazolyl penicillin. The antibiotic therapy is expected to be 3 to 14 days in duration. Obtained his/her informed consent after verbal and written information. Have a high probability for compliance with and completion of the study. Patients having a telephone available. Body Mass Index between 19 and 30. Exclusion Criteria: Participation in a clinical trial with an investigational product or drug within the 60 days prior to screening. Likeliness to be noncompliant with the protocol, or to be unsuitable to the study by the investigator for any reason. Pregnant or breastfeeding women; women planning to become pregnant during the study months. Presence of active diarrhea (3 or more loose or watery stools per 24 hour period). Daily consumption of probiotics, fermented milk and/or yogurt with probiotics. Known to have a previous reaction, including anaphylaxis, to any substance in composition of the study product (i.e. on-medicinal ingredients: Cellulose, hypromellose, magnesium stearate (vegetable source), ascorbic acid, Colloidal silicon dioxide). Presence of an active, non-controlled intestinal disease such as Crohn's Disease or ulcerative colitis. Regular use of proton pump inhibitors. Bowel surgery, artificial heart valve, history of rheumatic heart disease or infective endocarditis. A previous documented C. difficile infection < 3 months prior to study initiation. Immunosuppressive therapy or any health condition causing immunosuppression (including haematological malignancies, AIDS). Ongoing or recent use of antibiotic therapy in the 3 months prior to the study product first administration. Planned administration of antibiotics other than broad spectrum penicillins, cephalosporins, doxycycline, ciprofloxacin or isoxazolyl penicillin for the treatment of an infection. History of drug or alcohol abuse.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotic<br>Probiotic consumption during and after course of antibiotic | Dietary Supplement: Probiotic<br>* Probiotic formula, 10 billion CFU in total once a day for up to 3 weeks<br>* Other names: Howaru Restore;|
| Placebo Comparator: Placebo<br>Placebo consumed during and after course of antibiotic | Dietary Supplement: Placebo<br>* A capsule with microcrystalline cellulose matching the appearance and taste of the active comparator<br>* Other names: Microcrystalline cellulose as placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AAD | Incidence of diarrhoea defined as three or more loose or watery stools per a 24 h period. | Up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of diarrhoea | Number of continuous days of diarrhoea | Up to 21 days | 
| Fecal microbiota | Analysis of overall microbiota from all samples and of causative diarrhoeal agent from samples taken during diarrhoeal episode | Up to 21 days | 
| Safety profile | Evaluation of serious and non-serious adverse events | Up to 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibiotic, probiotic, antibiotic-associated diarrhoea, faecal microbiota