BacterioPHAGE for Gastrointestinal Health 2 Study

Study Overview
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Brief Summary
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The BacterioPHAGE for Gastrointestinal Health-2 study is designed to determine if a commercial bacteriophage product can increase the survival and efficacy of probiotic bacteria that will be concurrently administered. Bacteriophages may act as prebiotics, which are traditionally defined as indigestible dietary components that selectively enhance specific bacterial species in the intestines to confer a health benefit. In this study, the prebiotic is a unique combination of bacteriophages, or viruses that infect bacteria. These phages are generally regarded as safe for human consumption and are presumed to function by infecting pro-inflammatory E. coli strains in the gut. The removal of these strains alters the gut environment to allow growth of more favorable bacteria, and the lysis products of these E. coli may be assimilated by beneficial species to enhance their populations.The phage product, PreforPro, has shown to be effective in culture-based and animal studies, but its efficacy in increasing specific probiotic species has not been demonstrated in humans. The investigators have previously shown that PreforPro is both safe and tolerable in a human population and does not broadly disrupt the gut microbiota as would be seen with antibiotic treatment.

Detailed Description
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The commercial bacteriophage preparation,PreforPro, is often found as an ingredient in commercial probiotcs, so the goal of the current study is to determine if PreforPro consumption concurrent with probiotic usage improves probiotic survival and activity. A secondary goal of this study is to assess various physiologic parameters to determine whether consumption of PreforPro with a probiotic offers any health benefits beyond those of consuming a probiotic alone. The investigators will examine whether consumption of the PreforPro product increases detectable numbers of co-consumed probiotics and improves parameters in clinical outcomes related to glucose and lipid metabolism, cardiovascular function, inflammation of the intestines, or physical symptoms of gastrointestinal distress. To accomplish these research goals, the investigators will be seeking 200 male and female volunteers between 18-65 years old with BMI scores of 22 to 34.9. Recruitment will be by referral from local practitioners, email recruitment, and through word-of-mouth. Eligibility will be determined at the Colorado State University Food and Nutrition Clinical Research lab by a screening questionnaire and interview/assessment by the clinical coordinator. After securing consent, eligibility will be confirmed by taking anthropometric measures and participants falling within the BMI range will randomly be assigned to 1 of 3 treatment groups: (1) PreforPro+Bifidobacterium probiotic, (2) Bifidobacterium probiotic alone, or (3) placebo. Participants will consume the provided capsules daily for a period of four (4) weeks. Participants will be asked to visit the clinic at Visit 1 (Day 0) to pick up their supply of capsules and undergo sample collections (blood and stool) and analysis procedures, including weight/height, blood pressure, endothelial function analysis, gastrointestinal symptom screening, and blood and stool sample collection. At the end of the 4 week treatment period, all analyses will be repeated. This means that participants will undergo screening (either in person or by phone) and make a total of two (2) clinic visits during the study (baseline, and final visit). Participants will additionally be asked to complete two 24 hour dietary recalls prior to each clinic visit and track bowel movements using the Bristol Stool Scale throughout the study treatment period. All blood samples will be collected at Colorado State University by trained personnel. Fecal sample collection will be performed by the study participant with collection materials provided.

Official Title
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BacterioPHAGE for Gastrointestinal Health 2 Study

Conditions
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Mild Gastrointestinal Symptoms in Healthy Adults

Intervention / Treatment
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* Dietary Supplement: Bifidobacterium animals subsp. lactis BL04+PreforPro
* Dietary Supplement: Bifidobacterium animals subsp. lactis BL04
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy 18-65 years old BMI 20 to 34.9 Exclusion Criteria: individuals less than 18 years of age or greater than 65 years of age outside of the BMI range of 20-34.9 antibiotic or probiotic/prebiotic supplements within two months of the start of treatment use of statins, metformin, NSAIDs, MAO inhibitors, and botanical supplements that target the GI tract or gut microbiota current diagnosis of cancer, liver or kidney disease, gastrointestinal diseases, and metabolic disorders pregnant and breastfeeding women unable to adhere to the study requirements

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blinded, placebo controlled, parallel arm
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>15 mg capsule containing rice maltodextrin and medium chain coconut triglycerides | Other: Placebo<br>* One 15mg capsule taken orally each day<br>|
| Active Comparator: Bifidobacterium animals subsp. lactis BL04<br>15 mg capsule containing 1x 10^9 CFU Bifidobacterium animals subsp. lactis BL04 with rice maltodextrin and medium chain coconut triglycerides as a filler material | Dietary Supplement: Bifidobacterium animals subsp. lactis BL04<br>* One 15mg capsule taken orally each day<br>|
| Experimental: Bifidobacterium animals subsp. lactis BL04+PreforPro<br>15 mg capsule containing 1x 10^9 CFU Bifidobacterium animals subsp. lactis BL04 and 1x10^6 PFU of PreforPro (Commercial phage preparation) with rice maltodextrin and medium chain coconut triglycerides as a filler material | Dietary Supplement: Bifidobacterium animals subsp. lactis BL04+PreforPro<br>* One 15mg capsule taken orally each day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal Symptoms | A functional gastrointestinal questionnaire was used to assess pain and symptoms related to GI function, GI inflammation, Colon and small intestine pain | Four weeks | 
| Bowel Function | A record of all stools (using Bristol Stool Scale) was collected throughout the study | Four weeks | 
| Microbiota Analysis | 16s sequencing and phage plating was conducted to assess phage activity and microbiota associated changes. | Four weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Blood pressure will be measured on non-dominant arm using a Sphygmacor. Three consecutive measures will be taken after particioants have spent 5 minutes in a supine position. | Four weeks | 
| Endothelial Function | Endothelial function will be measured using EndoPat technology and expressed as Reactive Hyperemia Index (RHI) | Four Weeks | 
| Plasma Lipids | A single venous blood sample will be collected and 200 ul added to a Piccolo test cartridge for Plasma lipids, which measures total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Additionally these measures are used to calculate TC/HDL ratio. | Four weeks | 
| Comprehensive Metabolic Panel | A single venous blood sample will be collected and 200 ul added to a Piccolo test cartridge that measures glucose, creatinine, creatine kinase, blood urea nitrogen (BUN), total carbon dioxide, and chloride, sodium and potassium ions. | Four weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastrointestinal, probiotic, bacteriophage, Bifidobacterium animalis subspecies lactis