BacterioPHAGE for Gastrointestinal Health 2 Study (PHAGE2)

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.

Study Overview

• Status: Completed
• Conditions: Mild Gastrointestinal Symptoms in Healthy Adults
• Intervention / Treatment: Other: Placebo; Dietary supplement: Bifidobacterium animals subsp. lactis BL04; Dietary supplement: Bifidobacterium animals subsp. lactis BL04+PreforPro

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Fort Collins, Colorado, United States, 80523-1571
      • Colorado State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; 15 mg capsule containing rice maltodextrin and medium chain coconut triglycerides	Other: Placebo; One 15mg capsule taken orally each day
ACTIVE_COMPARATOR: Bifidobacterium animals subsp. lactis BL04; 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; One 15mg capsule taken orally each day
EXPERIMENTAL: Bifidobacterium animals subsp. lactis BL04+PreforPro; 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; One 15mg capsule taken orally each day

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Colorado State University
• Investigators: Principal Investigator: Tiffany L Weir, PhD, Colorado State University

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ACTUAL): October 31, 2019
• Study Completion (ACTUAL): March 31, 2020

Study Registration Dates

• First Submitted: August 7, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (ACTUAL): August 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 13, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: probiotic; gastrointestinal; bacteriophage; Bifidobacterium animalis subspecies lactis
• Other Study ID Numbers: 19-9145H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No