Gut Flora Dependent Metabolism of Dietary Phosphatidylcholine and Cardiovascular Disease (Glory)

The purpose of this study is to see if intestinal bacteria plays a role in choline metabolism (a form of choline monitored in this study is called phosphatidylcholine, also known as lecithin). This study will help to determine if choline metabolism is affected by short-term antibiotic therapy, and/or can be altered by probiotic therapy (e.g. in the form of eating yogurt).

Study Overview

• Status: Completed
• Conditions: Nutrition
• Intervention / Treatment: Other: Antibiotic (metronidazole and ciprofloxacin)/probiotic

Detailed Description

The purpose of this study is to see if intestinal bacteria plays a role in choline metabolism (a form of choline monitored in this study is called phosphatidylcholine, also known as lecithin). This study will help to determine if choline metabolism is affected by short-term antibiotic therapy, and/or can be altered by probiotic therapy (e.g. in the form of eating yogurt).

Metabolism is a process that turns foods we eat into fuel for our bodies. Choline is nutrient found in a type of fat commonly found in foods. There is evidence that choline metabolism by bacteria in the intestines may be linked to cardiac risk.

The purpose of this study is to see if intestinal bacteria plays a role in choline metabolism (a form of choline monitored in this study is called phosphatidylcholine, also known as lecithin). This study will help to determine if choline metabolism is affected by short-term antibiotic therapy, and/or can be altered by probiotic therapy (e.g. in the form of eating yogurt).

This single center study will randomize 30 normal, healthy volunteers to 1 of 3 groups:

Group 1: antibiotics for 1 week, followed by probiotics for 3 weeks; Group 2: antibiotics for 1 week, followed by no probiotics for 3 weeks. Group 3: no antibiotics for 1 week, followed by probiotics for 3 weeks.

The antibiotics to be used will be metronidazole (500 mg twice daily) and ciprofloxacin (500 mg daily) for one week. The probiotics to be used will be one serving size of standard flavored yogurt (approximately 170 g) twice daily for up to three weeks.

Study visits will occur at baseline, 1 week, and 4 weeks. Blood and urine samples will be collected at the start of each visit. Subjects will then eat 2 hard boiled eggs and be given a standard medical isotope. Additional blood samples will be obtained at 1, 2, 3, 4, and 6 hours, and a urine sample will be collected at 6 hours. Samples will be analyzed for choline levels, its byproducts, and isotope levels.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women age 18 years or above.
• Able to provide informed consent and comply with study protocol

Exclusion Criteria:

• Significant chronic illness or end-organ dysfunction, including known history of heart failure, renal failure, pulmonary disease, or hematologic diseases.
• Active infection or received antibiotics within 2 months of study enrollment
• Use of OTC probiotic within past 2 months, or ingestion of yogurt within past month
• Chronic gastrointestinal disorders, or intolerance to probiotic therapy
• Allergies to eggs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1; Group 1 (Antibiotics/probioitic):	Other: Antibiotic (metronidazole and ciprofloxacin)/probiotic; Antibiotic cocktail/yogurt as follows: Group 1: antibiotics for 1 week, followed by probiotics for 3 weeks; Group 2: antibiotics for 1 week, followed by no probiotics for 3 weeks. Group 3: no antibiotics for 1 week, followed by probiotics for 3 weeks.
Active Comparator: Group 2; Group 2 (Antibiotics/no-probiotic):	Other: Antibiotic (metronidazole and ciprofloxacin)/probiotic; Antibiotic cocktail/yogurt as follows: Group 1: antibiotics for 1 week, followed by probiotics for 3 weeks; Group 2: antibiotics for 1 week, followed by no probiotics for 3 weeks. Group 3: no antibiotics for 1 week, followed by probiotics for 3 weeks.
Active Comparator: Group 3; Group 3 (no-Antibiotics/probiotic):	Other: Antibiotic (metronidazole and ciprofloxacin)/probiotic; Antibiotic cocktail/yogurt as follows: Group 1: antibiotics for 1 week, followed by probiotics for 3 weeks; Group 2: antibiotics for 1 week, followed by no probiotics for 3 weeks. Group 3: no antibiotics for 1 week, followed by probiotics for 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome	Phosphatidylcholine derived gut flora metabolites	December 2016

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome Measures	Cardiometabolic risk markers	December 2016

Collaborators and Investigators

• Sponsor: The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: January 23, 2012
• First Submitted That Met QC Criteria: January 25, 2012
• First Posted (Estimate): January 26, 2012

Study Record Updates

• Last Update Posted (Estimate): March 3, 2016
• Last Update Submitted That Met QC Criteria: March 1, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: gut flora; phosphatidylcholine; choline metabolism; lecithin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Cytochrome P-450 CYP1A2 Inhibitors; Metronidazole; Anti-Bacterial Agents; Ciprofloxacin
• Other Study ID Numbers: 09-988