Next-Generation Synbiotic in Individuals With Overweight or Obesity

Supplementation With a Next-Generation Synbiotic in Individuals With Overweight or Obesity: A Triple-Blinded Randomized Controlled Clinical Trial

This study plans to evaluate the effect of consuming a symbiotic (probiotic + prebiotic) for 3 months on body weight, body composition, glucose sensitivity, and psychological parameters, as well as on gut and blood microbial composition. Synbiotic consumption is preceded by a 3-day antibiotic course to help ensure the opening of new niches (houses) for the upcoming beneficial bacteria.

Study Overview

• Status: Not yet recruiting
• Conditions: Overweight and Obesity
• Intervention / Treatment: Dietary supplement: Synbiotic Group; Other: Placebo Group

Detailed Description

This is a triple-blinded, randomized clinical trial in which participants will be allocated to one of two groups: 1) 3-day antibiotic followed by synbiotic consumption for 3 months or 2) 3-day antibiotic followed by placebo consumption for 3 months.

Blood and stool samples will be collected before the antibiotic, and before and after the symbiotic intervention in both groups.

Gut microbial composition will be analyzed through whole genome sequencing and blood microbial composition through 16S rRNA.

Glucose sensitivity will be measured through fasting glucose, fasting insulin, and HbA1c.

Body composition through DXA and BodPod will be measured before and after the symbiotic intervention.

Psychological questionnaires such as the Beck Anxiety and the Beck Depression Inventories, as well as the RED-9 questionnaire to respectively measure anxiety, depression, and food cravings, will be applied before and after the symbiotic intervention.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elisa Marroquin, Ph.D.; Phone Number: 817-257-1031; Email: E.Marroquin@tcu.edu
• Study Contact Backup: Name: Ryan Porter, Ph.D.; Phone Number: 817-257-6868; Email: r.porter@tcu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• be between 18-50 years of age
• have a BMI between 25.0-40.0

Exclusion Criteria:

• are following a vegetarian, vegan, carnivore, or keto diet
• currently taking metformin, GLP-1 agonists, insulin, or fiber
• have taken antiacids, laxatives, probiotics, or medication that affects your immune system in the past month
• pregnant, planning pregnancy during the study period, or lactating
• have a history of inflammatory bowel disease, colon cancer, or chronic polyps
• have been diagnosed with type 1 or type 2 diabetes
• have active cancer
• are currently participating in a weight loss intervention (dietetic or medication)
• have used antibiotics, antifungals, or antivirals in the past 3 months
• have had a history of recent (within 30 days) diarrhea illness
• have a known allergy to any component of the study product
• have had an acute inflammatory infection or inflammatory condition in the past 4 weeks
• have had >10% weight variation in the past 6 months
• have had any bariatric surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synbiotic Group; They will receive a 3-day antibiotic (Vancomycin 500 mg/3 times/day), followed by a 3-month symbiotic. The synbiotic that will be used in this trial contains the oligosaccharide-degrading probiotics, Akkermansia muciniphila and Bifidobacterium infantis; butyrate producers such as Clostridium beijerinckii, Anaerobutyricum hallii, and Clostridium butyricum; and chicory-derived inulin, a prebiotic dietary fiber.	Dietary supplement: Synbiotic Group; WBF-038: Noninfectious and nonhazardous lyophilized commensal bacteria (probiotics). Contains no genetically modified organisms (GMOs) and contains no animal ingredients or by-products, and were originally isolated from human sources. The (probiotic) strains are grown in a FDA registered food facility, adhering to Good Manufacturing Practice (GMP) conditions. Probiotic Ingredients: Clostridium butyricum WBSTR-0006, Clostridium beijerinckii WB-STR-0005, Anaerobutyricum hallii WB-STR-0008, Akkermansia muciniphila WBSTR-0001, and Bifidobacterium infantis The product also contains: Chicory inulin and oligofructose (prebiotic fiber), hypromellose (vegetarian capsule), fruit & vegetable juice (coloring agent), magnesium stearate and silica (flow agent for encapsulation); Other Names: The utilized synbiotic is Pendulum Glucose Control
Placebo Comparator: Placebo Group; They will receive a 3-day antibiotic (Vancomycin 500 mg/3 times/day), followed by a 3-month placebo.	Other: Placebo Group; Ingredients: Chicory inulin and oligofructose (prebiotic fiber, hypromellose (vegetarian capsule), fruit & vegetable juice (coloring agent), magnesium stearate and silica (flow agent for encapsulation).; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Body Fat Mass through DXA (percentage)	We will measure body fat mass by using DXA analysis.	These analyses will take place right before and right after the 3-month synbiotic/placebo intervention.
Total Body Fat Mass through BodPod (percentage)	We will measure body fat mass by using BodPod analysis.	These analyses will take place right before and right after the 3-month synbiotic/placebo intervention.
Fat Mass to Height (kg/m2)	We will measure body fat mass by using DXA analysis.	These analyses will take place right before and right after the 3-month synbiotic/placebo intervention.
Fat Mass (kg)	We will measure body fat mass by using BodPod analysis.	These analyses will take place right before and right after the 3-month synbiotic/placebo intervention.
Body Lean Mass to Height (kg/m2)	We will measure body lean mass by using DXA analysis.	These analyses will take place right before and right after the 3-month synbiotic/placebo intervention.
Fat Free Mass (%)	We will measure body lean mass by using BodPod analysis.	These analyses will take place right before and right after the 3-month synbiotic/placebo intervention.
Fat Free Mass (Kg)	We will measure body lean mass by using BodPod analysis.	These analyses will take place right before and right after the 3-month synbiotic/placebo intervention.
Visceral Fat Volume (cm3)	We will measure body visceral mass by using DXA and BodPod analysis.	These analyses will take place right before and right after the 3-month synbiotic/placebo intervention.
Visceral Fat Mass (grams)	We will measure body visceral mass by using DXA and BodPod analysis.	These analyses will take place right before and right after the 3-month synbiotic/placebo intervention.
Fasting Glucose (mg/dL)	We will measure fasting glucose after a 12h fast.	Blood samples will be taken before the antibiotic, before the synbiotic/placebo, and right after the 3-month synbiotic/placebo intervention.
Fasting Insulin (mIU/L)	We will measure fasting insulin after a 12h fast.	Blood samples will be taken before the antibiotic, before the synbiotic/placebo, and right after the 3-month synbiotic/placebo intervention.
HbA1c (%)	We will measure HbA1c after a 12h fast.	Blood samples will be taken before the antibiotic, before the synbiotic/placebo, and right after the 3-month synbiotic/placebo intervention.
Anxiety (number in 0-63 scale)	We will measure anxiety by using the Beck Anxiety inventory. The higher the number, the higher the anxiety levels.	These questionnaires will be applied right before and right after the 3-month synbiotic/placebo intervention.
Depression (number in 0-63 scale)	We will measure depression by using the Beck Depression inventory. The higher the number, the higher the depression.	These questionnaires will be applied right before and right after the 3-month synbiotic/placebo intervention.
Food cravings (number in 0-52 scale)	We will measure food cravings by using the Reward-based Eating Drive questionnaire (RED-9). The higher the number, the higher the cravings.	These questionnaires will be applied right before and right after the 3-month synbiotic/placebo intervention.
Gut Microbial Composition (depending on funding availability at the time of analysis)	We plan to measure gut microbial composition by performing whole metagenome sequencing previously stored in Zymo stool collection tubes.	Stool samples will be collected right before the antibiotic, right before the synbiotic/placebo intervention, and right after the 3-month synbiotic/placebo intervention.
Blood Microbial Composition (depending on funding availability at the time of analysis)	We plan to measure blood microbial composition by performing 16S rRNA in blood samples previously stored in Zymo blood collection tubes.	Blood samples will be collected right before the antibiotic, right before the synbiotic/placebo intervention, and right after the 3-month synbiotic/placebo intervention.
Body Weight (kg)	Body weight will be measured with a calibrated scale.	Measurements will take place at each of the 3 visits: right before the antibiotic, right before the synbiotic/placebo, and right after the 3-month synbiotic/placebo intervention.
Body Height (meters)	Body height will be measured with a stadiometer.	Measurement will take place at the first visit.

Collaborators and Investigators

• Sponsor: Texas Christian University
• Collaborators: Pendulum Therapeutics
• Investigators: Principal Investigator: Elisa Marroquin, Ph.D., Texas Christian University

Publications and helpful links

General Publications

• Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, Falony G, Raes J, Maiter D, Delzenne NM, de Barsy M, Loumaye A, Hermans MP, Thissen JP, de Vos WM, Cani PD. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019 Jul;25(7):1096-1103. doi: 10.1038/s41591-019-0495-2. Epub 2019 Jul 1.
• Perraudeau F, McMurdie P, Bullard J, Cheng A, Cutcliffe C, Deo A, Eid J, Gines J, Iyer M, Justice N, Loo WT, Nemchek M, Schicklberger M, Souza M, Stoneburner B, Tyagi S, Kolterman O. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001319. doi: 10.1136/bmjdrc-2020-001319.

Study record dates

Study Major Dates

• Study Start (Estimated): January 10, 2024
• Primary Completion (Estimated): December 20, 2024
• Study Completion (Estimated): May 20, 2025

Study Registration Dates

• First Submitted: December 20, 2023
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Estimated): January 19, 2024

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Obesity; Overweight
• Other Study ID Numbers: 2023-345

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant-level data can be shared only after authors and co-authors have published the material of their interest.
• IPD Sharing Time Frame: Data will be available only after authors and co-authors have published the material of their interest.
• IPD Sharing Access Criteria: Not available at this point. Recruitment has not started.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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