Effect of Nutrition Ingredients on Microbiota Modulation (VitaGut)

A Randomized, Double-blinded, Parallel, Placebo-controlled Pilot Study to Investigate the Effect of Nutrition Ingredients on Microbiota Composition in Healthy Adults

The objective of this study is to evaluate in healthy volunteers the time-dependent effect of daily consumption for four weeks of six different nutrition ingredients on relative abundance of microbial taxa in fecal samples. Second, the study looks at the time-dependent effect of six different nutrition ingredients on alpha and beta diversity of microbiota in fecal samples. Moreover, the time-dependent effect of six different nutrition ingredients on gastrointestinal symptoms and quality of life will be measured.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Dietary supplement: Vitamin B2; Dietary supplement: Vitamin C; Dietary supplement: Vitamin B2 + C; Dietary supplement: Vitamin A; Dietary supplement: Vitamin D3; Dietary supplement: Vitamin E; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ireland
  • Blackpool Cork
    • Cork, Blackpool Cork, Ireland, T12HH60
      • Atlantia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects willing and able to give written informed consent and to understand, to participate and to comply with the clinical study requirements;
2. Be between 20 and 50 years of age;
3. Has a BMI of between 18.5 - 30 Kg/m2;
4. Has a stable body weight (< 5% change) over the past 3-months;
5. Is in general good health, as determined by the investigator;
6. Willing to avoid consuming dietary supplements, prebiotic, probiotic, dietary or fibre rich supplements within 4 weeks prior to baseline visit, until the end of the study;
7. Willing to avoid liver consumption during the intervention
8. Maintain current level of physical activity;
9. Women of child-bearing potential using a non-hormonal contraceptive (e.g. IUD);
10. Willing to consume the investigational product daily for the duration of the study.

Exclusion Criteria:

1. Females are pregnant, lactating or wish to become pregnant during the study.
2. Are hypersensitive to any of the components of the test product;
3. Has taken antibiotics within the previous 3 months;
4. Has a history of drug and/or alcohol abuse at the time of enrolment;
5. Consumes greater than 2 servings/day of alcohol (e.g. >28 g ethanol/day);
6. Is a smoker;
7. Has made any major dietary changes in the past 3 months;
8. Subject is planning a sun or ski holiday over the duration of the study;
9. Planned major changes in life style (i.e. diet, dieting, exercise level, travelling) during the duration of the study;
10. Has an eating disorder;
11. Is vegetarian/vegan diet or has food allergies or other issues with foods that would preclude intake of the study products;
12. Is using fibre supplements or enemas;
13. Has a high fiber diet (i.e. >30 g) based on FFQ;
14. Has an active gastrointestinal disorder or previous gastrointestinal surgery,
15. If taking chronic medications (e.g., anti-hypertensive medications), they must have been taking the product for at least two months prior to screening and agree to maintain the same dosage throughout the study;
16. Has a metabolic, psychiatric, or gastrointestinal disease (i.e., diarrhoea, Crohn's disease, ulcerative colitis, irritable bowel syndrome, diverticulosis, stomach or duodenal ulcers, diabetes, hepatitis, HIV, cancer, etc.), with a history of such diseases;
17. Are severely immunocompromised (HIV positive, transplant patient, on antirejection medications, on a steroid for >30 days, or chemotherapy or radiotherapy within the last year);
18. Experiences alarm features such as weight loss, rectal bleeding, recent change in bowel habit (<3 months) or abdominal pain;
19. Have a malignant disease or any concomitant end-stage organ disease;
20. Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the trial;
21. Subjects may not be receiving treatment involving experimental drugs. If the subject has been in a recent experimental trial, these must have been completed not less than 60 days prior to this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vitamin B2; Daily dose of 75 mg Vitamin B2	Dietary supplement: Vitamin B2; One capsule of 75 mg Vitamin B2 once a day for 4 weeks; Other Names: Riboflavin
EXPERIMENTAL: Vitamin C; Daily dose of 500 mg Vitamin C	Dietary supplement: Vitamin C; One capsule of 500 mg Vitamin C once a day for 4 weeks
EXPERIMENTAL: Vitamin B2 + C; Daily dose of 75 mg Vitamin B2 and 500 mg Vitamin C	Dietary supplement: Vitamin B2 + C; One capsule of of 75 mg Vitamin B2 plus 500 mg Vitamin C once a day for 4 weeks
EXPERIMENTAL: Vitamin A; Daily dose of 250 µg Vitamin A	Dietary supplement: Vitamin A; One capsule of 250 µg Vitamin A once a day for 4 weeks
EXPERIMENTAL: Vitamin D3; Daily dose of 60 µg Vitamin D3	Dietary supplement: Vitamin D3; One capsule of 60 µg Vitamin D3 once a day for 4 weeks; Other Names: Cholecalciferol
EXPERIMENTAL: Vitamin E; Daily dose of 100 mg Vitamin E	Dietary supplement: Vitamin E; One capsule of 100 mg Vitamin E once a day for 4 weeks; Other Names: alpha-tocopherol
PLACEBO_COMPARATOR: Placebo; Daily dose of 575 mg microcrystalline cellulose	Dietary supplement: Placebo; One capsule of 575 mg microcrystalline cellulose once a day for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative abundance of microbial taxa in fecal samples as assessed by shotgun profiling based on shotgun sequencing	Changes from baseline in the treatment groups as compared to placebo of relative abundance of microbial taxa (operational taxonomic units)	from baseline to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alpha diversity of microbiota in fecal samples as assessed by shotgun profiling based on shotgun sequencing	Changes from baseline in the treatment groups as compared to placebo of alpha diversity assessed with shotgun sequencing (Shannon diversity, Estimated ChaoI index)	from baseline to 4 weeks
Beta diversity of microbiota in fecal samples as assessed by shotgun profiling based on shotgun sequencing	Changes from baseline in the treatment groups as compared to placebo of beta diversity assessed with shotgun sequencing (bray-curtis distance metrics)	from baseline to 4 weeks
Short-chain fatty acids concentrations in fecal samples	Changes from baseline in the treatment groups as compared to placebo of short-chain fatty acids using GC-MS (mM)	from baseline to 4 weeks
Ammonia concentrations in fecal samples	Changes from baseline in the treatment groups as compared to placebo of ammonia concentrations assessed with phenol-hypochlorite method (mg/L)	from baseline to 4 weeks
Cytokines and chemokines in blood	Changes from baseline in the treatment group as compared to placebo of cytokines and chemokines using immune assays (pg/mL)	from baseline to 4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electronic Gastrointestinal Symptom Rating Scale (GSRS) questionnaire	Changes from baseline in the treatment groups as compared to placebo of the GSRS. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms	from baseline to 4 weeks
Short Form 36 (SF-36) questionnaire	Changes from baseline in the treatment groups as compared to placebo of the quality of life questionnaire Short Form 36 (SF-36) questionnaire. The Short Form (SF)-36 generates a profile of health-related quality of life outcomes by measuring health across eight different dimensions: physical functioning, role limitation because of physical health, social functioning, vitality, bodily pain, mental health, role limitation because of emotional problems and general health. Responses to each question within a dimension are combined to generate a score from 0 to 100; where 100 indicates "good health".	from baseline to 4 weeks
Volatile organic compound levels in fecal samples	Changes from baseline in the treatment groups as compared to placebo of volatile organic compounds (intensity)	from baseline to 4 weeks

Collaborators and Investigators

• Sponsor: DSM Nutritional Products, Inc.
• Collaborators: Atlantia Food Clinical Trials
• Investigators: Principal Investigator: Timothy Dinan, Prof, Cork University Hospital

Publications and helpful links

General Publications

• Pham VT, Fehlbaum S, Seifert N, Richard N, Bruins MJ, Sybesma W, Rehman A, Steinert RE. Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study. Gut Microbes. 2021 Jan-Dec;13(1):1-20. doi: 10.1080/19490976.2021.1875774.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 20, 2018
• Primary Completion (ACTUAL): July 15, 2019
• Study Completion (ACTUAL): July 15, 2019

Study Registration Dates

• First Submitted: May 2, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (ACTUAL): September 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 30, 2020
• Last Update Submitted That Met QC Criteria: March 27, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Intestinal microbiota
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antioxidants; Vitamin D; Cholecalciferol; Vitamin E; Tocopherols; alpha-Tocopherol; Vitamins; Vitamin B Complex; Riboflavin; Vitamin A
• Other Study ID Numbers: 2017-12-19-VIT

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