Effect of the Use of Probiotic S. Boulardii on Acute Viral Inflammatory Diarrhea Diagnosed With Multiplex PCR.

Study Overview
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Brief Summary
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Acute diarrhea (AD) has been a public health problem throughout the history of Mexico. According to the epidemiological surveillance system, between 2008-2017, five to six million new cases of AD occurred per year. Clinical presentation of viral gastroenteritis ranges from an asymptomatic state to diarrhea with severe dehydration. Viral etiology can be difficult to differentiate from those of gastroenteritis caused by enteric bacteria based solely on clinical presentation, especially due to the presence of leukocytes in stool, since it was thought that only diarrhea of bacterial etiology was present and what defines it as acute inflammatory diarrhea; therefore, laboratory studies are essential to make a specific diagnosis. In addition to methylene blue test traditionally performed to describe the presence of leukocytes in stool, multiplex PCR is an automated system in which the extraction, amplification and detection of nucleic acid occurs in a single closed pouch. The panel includes for the etiological identification of bacteria, parasites and viruses. Probiotics are effective for acute infectious diarrhea caused by bacteria, but there are inconsistent results on the effectiveness of probiotics for diarrhea caused by viruses. It is important to note that there are no studies in the adult population with acute diarrhea of viral etiology identified by PCR Multiplex in our environment and the use of probiotics to reduce the period of convalescence. Mexico also lacks for detection tests to identify the pathogen, that can be used routinely in clinical practice, as other countries has shown the economical, clinical outcomes and patient satisfaction results with it. In a review, S. boulardii shows an effectiveness in 4 of the 6 studies where it was used as a treatment in acute adult viral diarrhea, where it was used as a treatment. Based on this review, because it considers the adult population, it will be used S. boulardii as a treatment in patients diagnosed with acute viral diarrhea, to reduce the days of presence of associated symptoms. The Patient Global Impression scale (PGI) is the Patient-reported outcomes counterpart to the Clinical Global Impressions scale. The PGIS are 1-item questionnaire that ask an individual patient to rate the severity of a specific condition at baseline and or to rate at endpoint the perceived change in his/her condition in response to therapy; in the other hand PGIC measures change in clinical status

Detailed Description
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Acute diarrhea (AD) has been a public health problem throughout the history of Mexico. According to the epidemiological surveillance system, between 2008 and 2017, five to six million new cases of AD occurred per year. The clinical presentation of viral gastroenteritis ranges from an asymptomatic state to diarrhea with severe dehydration. Viral etiology can be difficult to differentiate from those of gastroenteritis caused by enteric bacteria based solely on clinical presentation, especially due to the presence of leukocytes in stool, since it was thought that only diarrhea of bacterial etiology was present and what defines it as acute inflammatory diarrhea; therefore, laboratory studies are essential to make a specific diagnosis. In addition to methylene blue test traditionally performed to describe the presence of leukocytes in stool, Multiplex Polymerase Chain Reaction (PCR) is an automated system in which the extraction, amplification and detection of nucleic acid occurs in a single closed pouch. The panel includes for the etiological identification of bacteria, parasites and viruses. Probiotics are effective for acute infectious diarrhea caused by bacteria, but there are inconsistent results on the effectiveness of probiotics for diarrhea caused by viruses. It is important to note that there are no studies in the adult population with acute diarrhea of viral etiology identified by PCR Multiplex in our environment and the use of probiotics to reduce the period of convalescence. Mexico also lacks for detection tests to identify the pathogen, that can be used routinely in clinical practice, as other countries has shown the economical, clinical outcomes and patient satisfaction results with it. In a review, S. boulardii shows an effectiveness in 4 of the 6 studies where it was used as a treatment in acute adult viral diarrhea, where it was used as a treatment. Based on this review, because it considers the adult population, it wll be used S. boulardii as a treatment in patients diagnosed with acute viral diarrhea, to reduce the days of presence of associated symptoms. The Patient Global Impression scale (PGI) is the Patient-reported outcomes counterpart to the Clinical Global Impressions scale. The Patient Global Impression scale of Severity (PGIS) are 1-item questionnaire that ask an individual patient to rate the severity of a specific condition (single-state scales) at baseline and or to rate at endpoint the perceived change in his/her condition in response to therapy; in the other hand The Patient Global Impression scale of Change (PGIC) measures change in clinical status. Research question: What is the effect of the use of probiotic S. boulardii on acute inflammatory diarrhea of viral etiology diagnosed with multiplex PCR technique? Hypothesis: The use of S. boulardii in patients with acute viral inflammatory diarrhea diagnosed with the Multiplex PCR technique will decrease the days of associated symptoms and self-reported improvement. Main objective: To analyze the effect of the use of S. boulardii on acute inflammatory viral diarrhea diagnosed with the Multiplex PCR technique. Specifics: 1. To determine the incidence of viral pathogens in patients diagnosed with acute inflammatory viral diarrhea treated in the gastroenterology and coloproctology area. 2. To identify the incidence of associated symptoms in both groups in day 4 and 8 after diagnosis. 3. Compare the days of self-reported improvement by the patient between both groups using the PGIS and PGIC surveys.

Official Title
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Effect of the Use of Probiotic Saccharomyces Boulardii on Acute Viral Inflammatory Diarrhea Diagnosed With Multiplex PCR Technique, Randomized Clinical Trial (RCT).

Conditions
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Viral Diarrhea

Intervention / Treatment
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* Dietary Supplement: Saccharomyces boulardii (Floratil 600mg)
* Dietary Supplement: 3 capsules of placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients who give their informed consent, over 18 years of age, leukocytes in the stool, confirmed diagnosis of viral infection using the multiplex PCR Exclusion Criteria: Confirmed diagnosis of infection by bacteria and/or parasites, associated or not with viral etiology; autoimmune diseases or immunosuppressive treatment; previous administration of antibiotic treatment during the last 7 days; consumption of any type of probiotic in the last 7 days; known allergy to probiotic containing S. boulardii; Inflammatory Bowel Disease; positive test or clinical positivity to the current operational definition for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). patients who do not have medical insurance.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Randomized, double-blind clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S. boulardii<br>treatment arm group (3 capsules of Floratil 200mg®/day) | Dietary Supplement: Saccharomyces boulardii (Floratil 600mg)<br>* PGIC and PGIS assessment<br>* Other names: PGIC and PGIS assessment;|
| Placebo Comparator: Placebo<br>control group (3 capsules of placebo/day) | Dietary Supplement: 3 capsules of placebo<br>* PGIC and PGIS assessment<br>* Other names: PGIC and PGIS assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with S. boulardii on acute inflammatory viral diarrhea diagnosed with Multiplex PCR technique as treatment that have a change in the severity of their symptoms measured with PGIS and PGIC assessments at day 4 and day 8. | The Patient Global Impression scale (PGI) is the Patient-reported outcomes counterpart to the Clinical Global Impressions scale. The PGIS are 1-item questionnaire that ask an individual patient to rate the severity of a specific condition (single-state scales) at baseline and or to rate at endpoint the perceived change in his/her condition in response to therapy; in the other hand PGIC measures change in clinical status. | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with acute inflammatory viral diarrhea treated in the gastroenterology and coloproctology area | To determine the incidence of viral pathogens in patients diagnosed with acute inflammatory viral diarrhea treated in the gastroenterology and coloproctology area during the 12 month period; measured by applying the multiplex PCR test to determine the causative pathogen. | 365 days | 
| Number of subjects presenting associated symptoms in both groups in day 4 and 8 after diagnosis | To identify the incidence of associated symptoms, such as: fever and abdominal pain; assessed using the patient's daily record. | 8 days |