The Efficacy of PX0612 In The Treatment Of Irritable Bowel Syndrome

Study Overview
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Brief Summary
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IBS is a disorder of movement in the gut. People who have IBS may have diarrhea, constipation, or alternating bouts of both. IBS is not caused by injury or illness. Often the only way doctors can diagnose it is to rule out other conditions through testing.

Detailed Description
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Probiotics, particularly Bifidobacterium infantis, Sacchromyces boulardii, Lactobacillus plantarum and combination probiotics may help regulate how often people with IBS have bowel movements. Probiotics may also help relieve bloating from gas. Research is continuing to determine which probiotics are best to treat IBS. PX0612 PX0612 is a probiotic which is composed of the following ingredients contained in a veggie capsule, being one dose: Bacillus coagulans 200 million colony forming units 16.0mg Bacillus subtilis 100 million colony forming units 4.8mg Enterococcus faecium 100 million colony forming units 0.6mg Fructo-oligosacharride a nutrient for the packaged product 600.0mg Total 621.4 mg Bacillus coagulans is a non-pathogenic, Gram positive, spore forming bacteria that produces lactic acid. Though not normally found in the gut. Bacillus coagulans strains have been used as general nutritional supplements and agents to control constipation and diarrhea in humans and animals.

Official Title
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The Efficacy of PX0612 In The Treatment Of Irritable Bowel Syndrome: A Randomized, Double-Blind Placebo Controlled Clinical Trial

Conditions
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Irritable Bowel Syndrome With Diarrhea

Intervention / Treatment
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* Dietary Supplement: PX0612
* Dietary Supplement: Di-Calcium Phosphate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 - 65 years old Signed informed consent Mild to moderate (using Functional Bowel Disorder Severity Index (FBDSI)) IBS-Diarrhea patient: IBS definition will be based on Rome criteria; The symptoms of IBS must persist for at least 3 months and must include: Abdominal pain or discomfort which is relieved by defecation, and/or associated with a change in frequency of stool and/or consistency of stool At least two of the following, at least a quarter of occasions or days (25%): A. Altered stool frequency (> 3 bowel movements/day or < 3 bowel movements/week) B. Altered stool form (lumpy/hard or loose/watery stools) C. Altered stool passage (straining, urgency or feeling of incomplete evacuation) D. Passage of mucus E. Bloating or feeling of abdominal distention Note: Diarrhea is defined as having loose watery stools at least three times per day Exclusion Criteria: The patient will be excluded from the study if: Assessment by the treating investigator showed an evidence for cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematologic/immunologic, head, ears, eyes, nose and throat, dermatologic/psychiatric, allergy, major surgery or other diseases as revealed by history, physical examination and existing laboratory assessments which may interfere with the administration or 5 | P a g e PX0612 In The Treatment Of Irritable Bowel Syndrome: assessment of study medication. This should be confirmed by a pre-study medical examination performed 2 weeks prior the study. Pregnant or lactating Females at child bearing age will be excluded unless they are using acceptable birth control measures (i.e. implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual abstinence or a vasectomized partner) Patients requiring treatments with non-permitted medication (i.e. 5-HT3 antagonist, spasmolytics, anticholinergics, cholestyramine, anti flatulence agents, metoclopramide, gastric-anti secretory agents (proton pump inhibitors; for indications other than Gastroesophageal Reflux Disease (GERD)), narcotics, anti-diarrheal drugs, and systemic steroids) Patients requiring the use of antibiotics either in medicine form of natural (e.g. grapefruit seed extract, olive leaf extract, oil of oregano, colloidal silver and highly concentrated garlic preparations) Exercise and the use of complementary and alternative medicine for IBS symptoms (i.e. peppermint oil, cognitive behavior therapy) during the study should be maintained at the same level prior to the study. Patients exceeding the treatment limits of permitted medication [(more than 2 days/week during the study period): alginate, antacids and analgesics (limited to acetaminophen ≤ 1000 mg/day, acetylsalicylic acid or NSAIDS no more than 2 tablets/day), (stable dose throughout the study period, anti-depressants (must be on a stable dose > 3 months), fiber supplements, psyllium hydrophilic mucilloid, gastric anti secretory agents (only for GERD patients who are on a stable dose > 3 months; patients should be able to differentiate between IBS and GERD symptoms), acetylsalicylic acid ≤ 325 mg/day, sedatives. Deliverance medications: Mild laxatives only if necessary.]. Any other medications can be used without limits based on the clinical judgment of the treating investigator. Being in another clinical trial 4 weeks before entering the study Constipated IBS patients IBS-Diarrhea patients with un-treated lactose intolerance Regular use of probiotics or using other probiotics during the course of the study Patients allergic to milk or soy products Patients using catheters Patients presented with rectal bleeding, weight loss, iron deficiency anemia, nocturnal symptoms and a family history of colorectal cancer, inflammatory bowel disease and celiac spruce Patients over 50 diagnosed with Irritable Bowel Syndrome who have not had a colonoscopy in the last 5 years Patients who have allergies for the active ingredients or any of the exepients Patients presented with any immune-compromised condition (such as AIDS, lymphoma, long term corticosteroid treatment) Patients presented with nausea, vomiting and fever 6 |

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic PX0612<br>PX0612 is a probiotic contained in a veggie capsule. | Dietary Supplement: PX0612<br>* PX0612 is a probiotic contained in a veggie capsule.<br>|
| Placebo Comparator: Di-Calcium Phosphate<br>Patients in the 'placebo' group will receive the placebo capsules. The main ingredient in the placebo capsule is Di-Calcium Phosphate | Dietary Supplement: Di-Calcium Phosphate<br>* Patients in the 'placebo' group will receive the placebo capsules. The main ingredient in the placebo capsule is Di-Calcium Phosphate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Bowel Movements (Stool Frequency) Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. | For each patient stool frequency was measured as a number of bowel movements per day. To compare stool frequency before and after the treatment, the average for the first 2 run-in weeks (day 1 - day 14) and the last 2 weeks (day 78 - day 91) was calculated. A higher mean score indicates a better outcome, a greater reduction in bowel movements/day and is a positive change. Placebo group- min: -.43 max: 1.43 Study group- min: -.43 max: 1.50 | Baseline (days 1-14) compared to Weeks 10 and 11 of treatment (days 78-91) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in Upper Gastrointestinal Symptoms Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. | Mean change in heartburn between baseline (days 1-14) and weeks 10 and 11 (days 78-91) between the two groups. A higher mean value indicates a greater reduction in heartburn, better outcome. Analog Scale from 0-4 was used by participants to rate upper GI symptoms of heartburn (0= no heartburn, 4= incapacitating). Placebo group- Min: -2.00 Max: 3.00 Treatment group- Min: -2.00 Max: 2.00 | Baseline (days 1-14) compared to Weeks 10 and 11 of treatment (days 78-91) | 
| Differences in Upper Gastrointestinal Symptoms- Vomiting Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. | vomit scale used was from 0-4, the higher the number, the worse the outcome Mean change in vomiting between baseline and week 12 between the two groups. A higher mean value indicates a greater reduction in vomiting, better outcome. Analog Scale from 0-4 was used by participants to rate upper GI symptoms of vomiting(0= none, 4= incapacitating). Placebo group- Min: 0 Max: 0 Treatment group- Min: -3.00 Max: 0 | Baseline compared to Week 12 | 
| Changes in the Patient's Assessment of Their Quality of Life Using Short Form(SF)-36 Health Survey PCS (Physical Component Score) | Differences in quality of life phusical component score using SF-36 between the 'intervention' group and the 'placebo' group over the study period. Baseline PCS scores were compared to the end of the study time point. The mean difference between the 2 time points was measured. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. Scoring is based on software program. Placebo group- Min: -16.16 Max: 6.25 Treatment group- Min: -16.42 Max: 5.46 The total number of participants analyzed in each group differs as a result of the number of participants that either withdrew or were withdrawn in the study. Data were analyzed and compared for participants that completed the study. | Baseline compared to Week 12 (end of study) | 
| Differences in Abdominal Pain/Discomfort Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. | Outcome measure is the mean change of abdominal pain, on a scale of 0-4 (0= no pain, 4= incapacitating pain), between baseline and Weeks 10 and 11. A larger change in average abdominal pain indicates a greater reduction in mean abdominal pain score, better outcome. Min=-.067 for treatment group Min= -.99 for placebo group Max= 1.14 for treatment group Max= 1.63 for placebo group The total number of participants analyzed in each group differs as a result of the number of participants that either withdrew or were withdrawn in the study. Data were analyzed and compared for participants that completed the study. | Baseline (days 1-14) compared to Weeks 10 and 11 of treatment (days 78-92) | 
| Differences in Stool Consistency Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. | The stool consistency before and after the treatment was compared, the average for the first 2 run-in weeks (day 1 - day 14) and the last 2 weeks (day 78 - day 91) was calculated. A higher mean outcome indicates a greater reduction in loose stool/diarrhea (better outcome). Bristol Stool Chart (1=severe constipation to 7 =severe diarrhea) was the scale used for measurement. The participant reported outcomes were averaged at above time points for comparison. Min for placebo group: -.70 Max for treatment group: 2.57 Max for placebo group: 1.88 The total number of participants analyzed in each group differs as a result of the number of participants that either withdrew or were withdrawn in the study. Data were analyzed and compared for participants that completed the study. | Baseline (days 1-14) compared to Weeks 10 and 11 of treatment (days 78-92) | 
| Differences in Stool Frequency Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. | Number of stools/day | Baseline (days 1-14) compared to Weeks 10 and 11 of treatment (days 78-92) | 
| Differences in Upper Gastrointestinal Symptoms- Early Satiety | Differences Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. Change in rate of early satiety on a scale from 0-4 (higher the score, the worse the outcome) Mean change in early satiety between baseline and week 12 between the two groups. A higher mean value indicates a greater reduction in early satiety, better outcome. Analog Scale from 0-4 was used by participants to rate upper GI symptoms of early satiety (0= none, 4= incapacitating). Placebo group- Min: -2.00 Max: 1.00 Treatment group- Min: -2.00 Max: 2.00 | Baseline compared to Week 12 | 
| The Difference in Change of Postprandial Fullness Severity | Differences Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. Mean change in postprandial fullness between baseline and week 12 between the two groups. A higher mean value indicates a greater reduction in a postprandial fullness, better outcome. Analog Scale from 0-4 was used by participants to rate upper GI symptoms of postprandial fullness (0= no postprandial fullness, 4= incapacitating postprandial fullness). Placebo group- Min: -1.00 Max: 2.00 Treatment group- Min: -1.00 Max: 2.00 | Baseline compared to Week 12 | 
| Upper Gastrointestinal Symptoms of Prolonged Digestion | Differences Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. Mean change in prolonged digestion between baseline and week 12 between the two groups. A higher mean value indicates a greater reduction in prolonged digestion, better outcome. Analog Scale from 0-4 was used by participants to rate upper GI symptoms of prolonged digestion (0= none, 4= incapacitating). Placebo group- Min: -2.00 Max: 1.00 Treatment group- Min: -1.00 Max: 3.00 | Baseline compared to Week 12 | 
| Upper Gastrointestinal Symptom of Nausea | Differences Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. Mean change in nausea between baseline and week 12 between the two groups. A higher mean value indicates a greater reduction in nausea, better outcome. Analog Scale from 0-4 was used by participants to rate upper GI symptoms of nausea(0= none, 4= incapacitating). Placebo group- Min: 0.00 Max: 2.00 Treatment group- Min: -1.00 Max: 1.00 | Baseline and Week 12 | 
| FBDSI (Functional Bowel Disease Severity Index) | Differences Between the 'Intervention' Group and the 'Placebo' Group Over the Study Period. Mean change in FBDSI score between baseline and week 12 between the two groups. A higher mean value indicates a greater reduction in bowel disease severity, better outcome. Functional Bowel Disease Severity Index was the scale used to determine this outcome. The range on this scale is from 0-500, with 500 indicating the most severe functional bowel disease. Placebo group- Min: -10.00 Max: 350.00 Treatment group- Min: 0 Max: 300.00 | Baseline compared to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBS-D, diarrhea predominant