Clinical trial NCT06615986: Human Milk Oligosaccharide-Based Synbiotic Supplement for Intestinal Microbiota Dysbiosis
Official title: Evaluation of a Human Milk Oligosaccharide-Based Synbiotic Supplement for Intestinal Microbiota Dysbiosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Healthy Volunteers
Keywords: Gut Barrier
Intestinal Health
PLASMA LIPIDS
Artherosclerosis
Low-Density Lipoprotein (LDL)
Cholesterol
Lipoproteins
Human Milk Oligosaccharides (HMO)
Gut Microbiota
Symbiotic
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2024-09-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Background:

Human intestines are home to a complex gut flora, also called microbiome; this is a natural occurring community of bacteria, fungi, yeast, and viruses. Changes in the balances of the gut flora can lead to illnesses, such as diabetes, colorectal cancer, and inflammatory bowel diseases. Synbiotics are dietary supplements people take to maintain proper balances of their gut flora aiming to improve health.

Objective:

To find out if a synbiotic supplement can increase the type and amount of beneficial gut bacteria in healthy people as well as improve cardio-vascular protection markers. The supplement contains a natural sugar from human milk.

Eligibility:

Healthy people aged 18 years or older who eat a typical western diet. They must take no medications (with a few exceptions).

Design:

Participants will have 2 clinic visits.

The first visit will start with screening. They will have a blood test and wait around 2 hours for the results of the blood test. The test will determine if they are eligible for the study.

Eligible participants will have additional blood drawn during the screening visit. They will be given a kit to collect a stool sample at home with instructions. They may complete a 3-day food diary. They will meet with a nutritionist and a physician by phone, telehealth, or in person.

The supplement is a powder that is mixed with water or another noncarbonated drink. Participants will drink 2 doses per day. Each dose will be 1 hour before or after a meal.

The second visit will be about 8 weeks after the first. Participants may repeat the 3-day food diary and nutrition visit. The physical exam, blood tests, and stool sample will be repeated.

Detailed description: Study Description:

This pilot proof-of-principle (PoP) study will investigate mechanisms of action of a human milk oligosaccharide (HMO)-based synbiotic supplement, Cardiosyn (a combination of prebiotics and pro-biotics). Synbiotics for gut microbiota are known to exert multiple beneficial effects, including anti-inflammatory and antioxidant actions, and normalizing blood lipids and iron markers in healthy human subjects.

Objectives:

Primary Objective:

To measure changes in microbiome determined by the increase of the population of Lactobacillus Plantarum and Bifidobacterium Bifidum.

Secondary Objectives:

Measure the level of adherence to the symbiotic supplementation.

Measure the effect of the synbiotic supplementation in plasma.

Measure the effect of synbiotic supplementation on gut integrity.

Tolerability and GI symptoms secondary to gut microbiome changes.

Tertiary/Exploratory Objectives:

Identify possible associations between the gut microbiome change and biomarkers.

Endpoints: Primary Endpoint:

At least an increase in the population of Lactobacillus Plantarum and Bifidobacterium Bifidum.

Secondary Endpoint:

Reported intake by the subject and counting the number of the remaining supplement

Biomarkers such as serum and fecal calprotectin, hs-CRP, serum iron, hepcidin, hemoglobin, lipid profile and TMAO

Measurement of gut integrity marker (serum zonulin) in plasma

Number of participants that tolerated study supplement for full duration of study

Number of participants with GI reported symptoms according to CTCAE v5.0

Tertiary/Exploratory Endpoints:

Measurement of changes of microbiome and biomarkers in plasma (16S RNA microbiota analysis initially with potential for more extensive and novel analysis).

Eligibility criteria: * INCLUSION CRITERIA:
* Healthy males and females between the ages 18 to 99.
* Subject understands the protocol and provides written, informed consent in addition to a willingness to comply with specified follow-up evaluations.
* Subjects taking no medications, with a few exceptions (sporadic medication and medications known to not significantly affect the microbiome, per PI discretion).
* Screening labs within normal levels. Deviations of the screening labs from normal levels up to CTCAE v5, grade 1 are allowed per PI discretion.

EXCLUSION CRITERIA:

* Pregnancy or women currently breastfeeding.
* Subjects currently on other prebiotics and/or probiotics supplementation.
* Subjects that are vegetarians or vegans or not on a typical western diet.
* Subjects planning to initiate new medications or already taking medications that may interfere or modify gut microbiome.
* Subjects with allergy or known hypersensitivity to any components of the supplement.
* Subjects with weight changes greater than 20% over the past 3 months.
* Subjects planning a significant change in diet or exercise levels.
* Subjects with chronic diarrhea, gastric bypass or lap-band procedures, ostomies, bowel motility problems, or other known conditions that could affect intestinal fat absorption.
* Anticipated surgery during the study period.
* Any other reason or clinical condition that the Investigators judge would interfere with study participation and/or be unsafe for a participant.

Primary outcomes:
measure: Mean change in population of Lactobacillus plantarum and Bifidobacterium bifidum
timeFrame: 8 weeks
Secondary outcomes:
measure: Reported intake by the subject and counting the number of remaining supplement
timeFrame: 8 weeks
measure: Mean change of biomarkers such as serum and fecal calprotectin, hs-CRP, serum iron, hepcidin, hemoglobin in plasma
timeFrame: 8 weeks
measure: Fold increase in Lactobacillus or Bifidobacterium over baseline
timeFrame: 8 weeks
measure: Number of participants that tolerated symbiotic supllementation
timeFrame: 8 weeks
measure: Number of gastrointestinal symptoms reported by participants using Common Terminology Criteria for Adverse Events version 5.0
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
name: Marcelo J Amar, M.D.
role: PRINCIPAL_INVESTIGATOR
References: