PHAGE Study: Bacteriophages as Novel Prebiotics

Study Overview
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Brief Summary
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The PHAGE study is designed to determine if a commercial prebiotic product can change the composition of bacteria in the gut for improved intestinal health. A prebiotic is defined as an indigestible dietary component that selectively enhances specific bacterial species in the intestines to confer a health benefit. In this study, the prebiotic a unique combination of bacteriophages, or viruses that infect bacteria. These phages are generally regarded as safe for human consumption and work by infecting bad bacteria in the gut, which allows beneficial bacteria populations to increase. The product, PreforPro, has shown to be effective in culture-based and animal studies, but its efficacy has not been demonstrated in humans. The goal of this study is to see if PreforPro consumption improves gut bacteria profiles in individuals relative to a placebo control and is associated with reduced incidence and severity of gastrointestinal distress.

Detailed Description
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The goal of this study is to see if consumption of PreforPro, a commercially available prebiotic dietary supplement consisting of a mixture of bacteriophages, improves gut bacteria profiles in individuals relative to a placebo control. Secondary outcome measures include determining changes in comprehensive metabolic profiles, inflammatory markers (systemic and local), microbial metabolites, and perceptions of gastrointestinal distress. To accomplish these research goals, 40 male and female volunteers between 18-65 years old with BMI scores of 20 to 34.9 who suffer from mild gastrointestinal distress will be enrolled.Recruitment will be by referral from local practitioners and through email solicitations. Eligibility will be determined at the Colorado State University Medical Nutrition Therapy Laboratory (MNTL) by a screening questionnaire and interview/assessment by the clinical coordinator. After determining eligibility and securing consent, participants will randomly be assigned to 1 of 2 treatment groups: prebiotic or placebo. Participants will consume one capsule daily of respective treatments for a period of four (4) weeks. At the beginning and end of the 4 week treatment periods blood and stool samples will be collected at the Human Performance Clinical Research Laboratory (HPCRL). This means that participants will make a total of four (4) clinic visits during each treatment period. Following the initial treatment period, all participants will be required to undergo a wash-out period for two (2) weeks. Upon completion of the wash-out period, participants will switch treatment groups for a period of four (4) weeks. Clinic visits at baseline and 4-weeks for collection of stool and blood samples will also be conducted during the second treatment period. Study participants will be required to provide a total of four (4) fecal samples and four (4) fasting blood samples. Additionally, study participants will be required to provide a weekly assessment of GI symptoms during the two treatment periods. All blood samples will be collected at Colorado State University by trained professionals. Fecal sample collection will be performed by the study participant with collection materials provided by study personnel. Both participants and researchers will be blinded during the course of the intervention and throughout the data analysis period. Blinding will be conducted by individuals from Deerland Enzymes, the company that is providing the capsules for intervention.

Official Title
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PreforPro: A Randomized, Placebo Controlled Crossover Study

Conditions
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Gastrointestinal Disorder, Functional

Intervention / Treatment
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* Dietary Supplement: Bacteriophage mixture
* Other: Placebo Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults 18-65 years old Mild to moderate GI distress (self-assessed) Exclusion Criteria: Pregnant or breastfeeding Diagnosed GI disease (Celiac, peptic ulcer, ulcerative colitis, Crohn's disease, cancer, or other gastrointestinal or metabolic diseases) Antibiotic use in the past 2 months Use of NSAIDS, statins, metformin, and other drugs known to modify the gut microbiota BMI less than 18.0 or greater than 35.0

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The PHAGE Study is a randomized, double-blind, placebo controlled crossover trial that investigates the utility of four supplemental bacteriophage strains (LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae) to modulate the gut microbiota, and therefore ameliorate common inflammation-related GI distress symptoms (e.g., gas, bloating, diarrhea, constipation, etc) experienced by healthy individuals.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Comparator<br>Placebo control: 1 capsule containing rice maltodextrin consumed 1x daily for 28 days. | Other: Placebo Control<br>* Placebo control capsule consisting of rice maltodextrin<br>* Other names: rice maltodextrin;|
| Experimental: Experimental<br>Bacteriophage mixture: 1 capsule containing rice maltodextrin and a mixture of 4 bacteriophages consumed 1x daily for 28 days. | Dietary Supplement: Bacteriophage mixture<br>* Four bacteriophage strains: LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae.<br>* Other names: PreforPro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiota modulation | Use of 16s rRNA sequencing of stool samples to determine whether the administered interventions resulted in changes to microbial composition. | Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local inflammation | Inflammation in the bowels will be assessed by use of ELISA test for fecal calprotectin. | Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2 | 
| Systemic Inflammation | Systemic inflammation will be assessed by an ELISA test for CRP and circulating cytokines and immune factors. | Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dysbiosis, gut microbiota, bacteriophage, irritable bowel syndrome, gastrointestinal distress, prebiotic