PHAGE Study: Bacteriophages as Novel Prebiotics

Gastrointestinal Disorder, Functional Clinical Trial

Official title:

PreforPro: A Randomized, Placebo Controlled Crossover Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03269617
• Other study ID #: 16-6666HH
• Status: Completed
• Phase: N/A
• Start date: October 1, 2016
• Est. completion date: May 30, 2017

Study information

• Verified date: April 2019
• Source: Colorado State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: May 30, 2017
• Est. primary completion date: May 30, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Digestive System Diseases
• Gastrointestinal Diseases
• Gastrointestinal Disorder, Functional

Intervention

Dietary Supplement:
• Bacteriophage mixture
Four bacteriophage strains: LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae.

Other:
• Placebo Control
Placebo control capsule consisting of rice maltodextrin

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Colorado State University	George Mason University, Metabiomics Corp

References & Publications (2)

Febvre HP, Rao S, Gindin M, Goodwin NDM, Finer E, Vivanco JS, Lu S, Manter DK, Wallace TC, Weir TL. PHAGE Study: Effects of Supplemental Bacteriophage Intake on Inflammation and Gut Microbiota in Healthy Adults. Nutrients. 2019 Mar 20;11(3). pii: E666. do — View Citation

Gindin M, Febvre HP, Rao S, Wallace TC, Weir TL. Bacteriophage for Gastrointestinal Health (PHAGE) Study: Evaluating the Safety and Tolerability of Supplemental Bacteriophage Consumption. J Am Coll Nutr. 2019 Jan;38(1):68-75. doi: 10.1080/07315724.2018.14 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Microbial metabolism	Fermentation by microbes in the gut will be assessed by measuring fecal short chain fatty acid concentrations.	Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
Other	Circulating lipids	Total cholesterol, LDL, HDL, and triglycerides will be determined in venous blood using a clinical analyzer (Piccolo Xpress).	Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
Other	Comprehensive metabolic panel	Basic metabolic parameters such as fasting glucose, and levels of BUN, creatinine, and liver enzymes will be determined from a single 200 ul aliquot of venous blood using a CMP clinical analysis panel for Piccolo Xpress.	Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
Other	GI symptom self-assessment	Participants will complete a validated questionnaire to track changes in GI symptoms.	Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
Primary	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	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
Secondary	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