Safety, Tolerability, and Biosignature of Humanized Prebiotics in Healthy Adults

Study Overview
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Brief Summary
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This study aims to establish the safety of a 15 g/day dose of pure prebiotics ß(1-4) galacto-oligosaccharides (GOS) and GOS enriched with N-Acetyl-D-lactosamine, a building block of gut glycoproteins and human milk oligosaccharides (LAcNac, humanized GOS, hGOS) in healthy adult individuals. The safety and tolerability of the dose and the biological signature of GOS and hGOS in healthy adults will be established through a pilot clinical trial to assess GOS and hGOS effects vs placebo on (i) gastrointestinal adverse effects as measured by the Gastrointestinal Symptom and Severity Checklist (GSSC), (ii) increased abundance of beneficial gut bacteria and restoration of the gut microbiome saccharolytic potential, (iii) modulation of biomarkers of inflammation and (iv) evaluation of intestinal barrier function.

Official Title
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Safety, Tolerability, and Biosignature of Humanized Prebiotics in Healthy Adults

Conditions
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Intestinal Health

Intervention / Treatment
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* Dietary Supplement: Humanized galacto-oligosaccharides (hGOS)
* Dietary Supplement: Galacto-oligosaccharides (GOS)
* Other: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants will be nonsmokers and well-nourished according to standard anthropometric criteria with BMI between 18.5 and 32. Individuals must be able to give informed consent. Subjects willing and able to: consume prebiotics or placebo preparations for a period of 4 weeks. Record daily food consumption using the CDC My Food Diary questionnaire. provide stool and blood (via venipuncture) samples. Enrollment will not be restricted based on race, ethnicity, or gender. The subject population will reflect the population providing a broad selection of individuals to allow enrollment of subjects from all races, ethnicities, and genders, as represented in North Carolina state. Exclusion Criteria: Less than 18 years of age or older than 55 years of age Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 3 arms: GOS, hGOS, or placebo, with 16 participants per arm.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lactosamine-enriched humanized galacto-oligosaccharides (hGOS)<br>The treatment will consist of 10-15 g/day of hGOS, which will be provided to participants as a powder that can be added to any non-alcoholic beverage. The intervention will last for 4 weeks since the research team has shown in adult individuals that a 4-wk period allows for the observation of changes to the gut microbiome. The study will end after the second time-point sample collection at 4 weeks. | Dietary Supplement: Humanized galacto-oligosaccharides (hGOS)<br>* 10-15 g/day of hGOS, which will be provided to participants as a powder that can be added to any non-alcoholic beverage<br>* Other names: hGOS;|
| Experimental: galacto-oligosaccharides (GOS)<br>The treatment will consist of 10-15 g/day of GOS, which will be provided to participants as a powder that can be added to any non-alcoholic beverage. The intervention will last for 4 weeks since the research team has shown in adult individuals that a 4-wk period allows for the observation of changes to the gut microbiome. The study will end after the second time-point sample collection at 4 weeks. | Dietary Supplement: Galacto-oligosaccharides (GOS)<br>* 10-15 g/day of GOS, which will be provided to participants as a powder that can be added to any non-alcoholic beverage.<br>* Other names: GOS;|
| Placebo Comparator: Placebo<br>The placebo comparator treatment will consist of 10-15 g/day placebo powder, that can be added to any non-alcoholic beverage. The intervention will last for 4 weeks to mirror the treatment arms. The study will end after the second time-point sample collection at 4 weeks. | Other: Matching Placebo<br>* 10-15 g/day powdered corn syrup comprised of fructose, glucose, and an inert cellulose material that matches the consistency, color sweetness, and taste of the prebiotics, that can be added to any non-alcoholic beverage.<br>* Other names: Sugar powder;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean GSSC Scores | Safe and tolerable dose of hGOS and GOS in healthy adult individuals will be measured using the Gastrointestinal Symptom and Severity Checklist (GSSC) score. The GSSC is a 38-item interviewer-administered structured questionnaire designed to assess symptoms of gastrointestinal symptoms with scores ranging from 0 to 114, with higher scores indicating more gastrointestinal symptoms. | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Percent Abundance of Beneficial Bacteria | The abundance of beneficial bacteria of interest include Bifidobacterium and Akkermansia as measured by whole genome sequencing of stool. | Baseline, Week 4 | 
| Change in Interleukin-1α Concentration | Modulation of inflammatory biomarker as measured by the MCYTOMAG-70K (Milliplex) reported in pg/mL. | Baseline, Week 4 | 
| Change in Interleukin-1ß Concentration | Modulation of inflammatory biomarker as measured by the MCYTOMAG-70K (Milliplex) reported in pg/mL. | Baseline, Week 4 | 
| Change in Interleukin-2 Concentration | Modulation of inflammatory biomarker as measured by the MCYTOMAG-70K (Milliplex) reported in pg/mL. | Baseline, Week 4 | 
| Change in Interleukin-6 Concentration | Modulation of inflammatory biomarker as measured by the MCYTOMAG-70K (Milliplex) reported in pg/mL. | Baseline, Week 4 | 
| Change in Interleukin-8 Concentration | Modulation of inflammatory biomarker as measured by the MCYTOMAG-70K (Milliplex) reported in pg/mL. | Baseline, Week 4 | 
| Change in Interleukin-12 Concentration | Modulation of inflammatory biomarker as measured by the MCYTOMAG-70K (Milliplex) reported in pg/mL. | Baseline, Week 4 | 
| Change in Tumor Necrosis Factor Alpha (TNF-α) Concentration | Modulation of inflammatory biomarker as measured by the MCYTOMAG-70K (Milliplex) reported in pg/mL. | Baseline, Week 4 | 
| Change in Interferon gamma (IFNγ) Concentration | Modulation of inflammatory biomarker as measured by the MCYTOMAG-70K (Milliplex) reported in pg/mL. | Baseline, Week 4 | 
| Change in C-Reactive Protein Concentration | Modulation of inflammatory biomarker as measured in blood by commercial enzyme-linked immunosorbent assay (ELISA) kit reported in mg/L. | Baseline, Week 4 | 
| Change in Zonulin Concentration | Used to assess modulation in intestinal barrier function in blood and reported in ng/mL. | Baseline, Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prebiotics, Galactooligosaccharides, Lactosamine