## Protocol Section
### Identification Module
**NCT ID:** NCT06425081

**Acronym:** VIAB2L

**Brief Title:** Investigating the Impact of Humiome B2 (Colon Delivered Riboflavin) and Riboflavin-overproducer Probiotic Strain Limosilactobacillus Reuteri AMBV339 on Intestinal and Vaginal Microbiome and Health of Healthy Adult Women (The VIAB2L Project)

**Official Title:** Investigating the Impact of Humiome B2 (Colon Delivered Riboflavin) and Riboflavin-overproducer Probiotic Strain Limosilactobacillus Reuteri AMBV339 on Intestinal and Vaginal Microbiome and Health (The VIAB2L Project)

#### Organization Study ID Info
**ID:** 2023-07-14-VIAB
#### Organization
**Class:** INDUSTRY
**Full Name:** DSM Nutritional Products, Inc.
### Status Module
#### Completion Date
**Date:** 2024-12-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-24

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-12-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-08
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Universiteit Antwerpen

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** DSM Nutritional Products, Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The goal of this clinical trial is to learn if the probiotic strain Limosilactobacillus reuteri AMBV339 or colon-delivered riboflavin or their combination can change the gut microbiome. It will also learn about the safety of the investigational product. The main questions it aims to answer are:

Do the probiotic strain Limosilactobacillus reuteri AMBV339 or colon-delivered riboflavin or their combination modify gut microbiome? Do the probiotic strain Limosilactobacillus reuteri AMBV339 or colon-delivered riboflavin or their combination modify gut microbiome?

Researchers will compare the probiotic strain Limosilactobacillus reuteri AMBV339 or colon-delivered riboflavin or their combination to a placebo (a look-alike substance that contains no drug) to see if they can change gut and vaginal microbiome. Intervention period is 28 days.

**Detailed Description:** The goal of this clinical trial is to learn if the probiotic strain Limosilactobacillus reuteri AMBV339 or colon-delivered riboflavin or their combination can change the gut microbiome. It will also learn about the safety of the investigational product. Participants are healthy adult females of reproductive age and will take the investigational products for 28 days. There will be several non-invasive measurements, including but not limited to gut microbiome measured in faecal samples and vaginal microbiome measured in vaginal samples. They will fill some questionnaires about their general health.

The investigational product is a probiotic strain (1 billion CFU), colon-delivered riboflavin,(10mg) and their combination.

Participants will:

Take the probiotic strain Limosilactobacillus reuteri AMBV339 or colon-delivered riboflavin or their combination or a placebo every day for 28 days.

Visit the clinic once every 2 weeks for checkups and tests. Keep a diary of their bowel habits and provide fecal and vaginal sample at visits.

### Conditions Module

**Conditions:**

- Microbial Colonization

**Keywords:**

- Probiotic

- vitamin

- Riboflavin

- Vitamin B2

- lactobacillus

- microbiome

- gut microbiome

- vaginal microbiome

- women's health

- gut health

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Double-blinded, randomized and placebo-controlled clinical trial

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** The study will double blinded

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** SCREENING

#### Enrollment Info

**Count:** 200

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Probiotic strain, 1B CFU per day for 28 days in capsule format

**Intervention Names:**

- Dietary Supplement: Limosilactobacillus reuteri AMBV339

**Label:** L. reuteri AMBV339 (1x109 CFU per capsule)

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** 73 mg colon delivered riboflavin containing 10 mg pure riboflavin

**Intervention Names:**

- Dietary Supplement: Humiome B2

**Label:** Humiome B2

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Description:** Combination of Arm 1 and Arm 2

**Intervention Names:**

- Dietary Supplement: L. reuteri AMBV339 ca. 1x109 CFU per capsule + Humiome B2

**Label:** L. reuteri AMBV339 ca. 1x109 CFU per capsule + Humiome B2

**Type:** ACTIVE_COMPARATOR

#### Arm Group 4

**Description:** Microcrystalline cellulose

**Intervention Names:**

- Dietary Supplement: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- L. reuteri AMBV339 (1x109 CFU per capsule)

**Description:** Limosilactobacillus reuteri AMBV339 is a probiotic strain

**Name:** Limosilactobacillus reuteri AMBV339

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- Humiome B2

**Description:** Colon-delivered Riboflavin

**Name:** Humiome B2

**Type:** DIETARY_SUPPLEMENT

#### Intervention 3

**Arm Group Labels:**

- L. reuteri AMBV339 ca. 1x109 CFU per capsule + Humiome B2

**Description:** Combination of supplements used in arm 1 and 2

**Name:** L. reuteri AMBV339 ca. 1x109 CFU per capsule + Humiome B2

**Type:** DIETARY_SUPPLEMENT

#### Intervention 4

**Arm Group Labels:**

- Placebo

**Description:** Microcrystalline cellulose

**Name:** Placebo

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Other Outcomes

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on the excreted levels of riboflavin (in urine). Comparisons will be made between the active groups and with placebo.

**Measure:** Excreted levels of riboflavin (in urine)

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of 28 days of supplementation with either Humiome B2 or L. reuteri AMBV339 or their combination on key anti-inflammatory and cytokine markers in the vagina , assessed by ELISA (e.g., beta-defensin-1 and secretory IgA as well as a broad panel of protein biomarkers). Comparisons will be made between the active groups and with placebo.

**Measure:** Immune markers

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on GIT health will be measured using the GSRS questionnaire. Comparisons will be made between the active groups and with placebo.

**Measure:** General GIT health

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on general Vaginal health will measured using a Ph meter. Comparisons will be made between the active groups and with placebo.

**Measure:** General Vaginal health

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on host Body temperature using a thermometer. Comparisons will be made between the active groups and with placebo.

**Measure:** General host health: Body temperature

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on host Pulse rate using a pulse rate monitor. Comparisons will be made between the active groups and with placebo.

**Measure:** General host health: Pulse rate

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on host Respiration rate by counting the number of chest rises per minute in rest mode. Comparisons will be made between the active groups and with placebo.

**Measure:** General host health: Respiration rate

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on host Blood pressure sphygmomanometer. Comparisons will be made between the active groups and with placebo.

**Measure:** General host health: Blood pressure

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on user satisfaction levels based on a simple questionnaire of 10 point scale of how they felt before and after intervention (0 being the lowest point and 10 being the highest point). Comparisons will be made between the active groups and with placebo.

**Measure:** User satisfaction of investigational product

**Time Frame:** day 0 - day 28

#### Primary Outcomes

**Description:** 1. To investigate if daily supplementation (for 28 days) with either Humiome B2 or Limosilactobacillus reuteri AMBV339 or their combination modulate the microbiome composition (relative abundance of different taxa) in the gastrointestinal tract (GIT). Comparisons will be made between the active groups and with placebo.

**Measure:** Microbiome change in GUT

**Time Frame:** day 0 - day 28

#### Secondary Outcomes

**Description:** To investigate if daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination modulate the microbiome composition (relative abundance of different taxa) in the vagina. Comparisons will be made between the active groups and with placebo.

**Measure:** Microbiome change in vagina

**Time Frame:** day 0 - day 28

**Description:** 2. To investigate if daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination modulate the microbiome diversity in the GIT. Comparisons will be made between the active groups and with placebo.

**Measure:** Gut microbiome diversity

**Time Frame:** day 0 - day 28

**Description:** To investigate if daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination modulate the microbiome diversity in the vagina. Comparisons will be made between the active groups and with placebo.

**Measure:** Vaginal microbiome diversity

**Time Frame:** day 0 - day 28

**Description:** To investigate if daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination modulate the relative abundance levels of keystone taxa in the GIT. Comparisons will be made between the active groups and with placebo.

**Measure:** Keystone bacterial taxa in gut

**Time Frame:** day 0 - day 28

**Description:** To investigate if daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination modulate the relative abundance levels of keystone taxa in the vagina. Comparisons will be made between the active groups and with placebo.

**Measure:** Keystone bacterial taxa in vagina

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either L. reuteri AMBV339 or its combination with Humiome B2 on the presence, persistence and/or engraftment of L. reuteri AMBV339 in the GIT during the intervention and 1 week after the end of supplementation. Comparisons will be made between the active groups and with placebo.

**Measure:** Presence of L. reuteri AMBV339 in gut

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either L. reuteri AMBV339 or its combination with Humiome B2 on the presence, persistence and/or engraftment of L. reuteri AMBV339 in the vagina during the intervention and 1 week after the end of supplementation. Comparisons will be made between the active groups and with placebo.

**Measure:** Presence of L. reuteri AMBV339 in vagina

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on co-occurrence patterns of different bacterial taxa in the GIT, with particular attention to the possible role of riboflavin as an extracellular electron transfer molecule. Comparisons will be made between the active groups and with placebo.

**Measure:** co-occurrence patterns of different bacterial taxa in the Gut microbiome

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on co-occurrence patterns of different bacterial taxa in the vagina, with particular attention to the possible role of riboflavin as an extracellular electron transfer molecule. Comparisons will be made between the active groups and with placebo.

**Measure:** co-occurrence patterns of different bacterial taxa in the vaginal microbiome

**Time Frame:** day 0 - day 28

**Description:** To investigate if daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination modulate the metabolomic profile in the GIT. Comparisons will be made between the active groups and with placebo.

**Measure:** Gut metabolomic profile

**Time Frame:** day 0 - day 28

**Description:** To investigate if daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination modulate the metabolomic profile in the vagina. Comparisons will be made between the active groups and with placebo.

**Measure:** Vaginal metabolomic profile

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on the levels of riboflavin in the GIT. Comparisons will be made between the active groups and with placebo.

**Measure:** levels of riboflavin in the gut

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination for 28 days on the levels of riboflavin in the vagina. Comparisons will be made between the active groups and with placebo.

**Measure:** levels of riboflavin in vagina

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of 28 days of supplementation with either Humiome B2 or L. reuteri AMBV339 or their combination on the systemic levels of riboflavin (in blood). Comparisons will be made between the active groups and with placebo.

**Measure:** systemic levels of riboflavin (in blood)

**Time Frame:** day 0 - day 28

**Description:** To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on the levels of short-chain fatty acids (SCFAs) and related metabolites in the GIT. Comparisons will be made between the active groups and with placebo.

**Measure:** Short chain Fatty Acid (SCFA) levels in gut

**Time Frame:** day 0 - day 28

**Description:** 7. To investigate the effect of daily supplementation (for 28 days) with either Humiome B2 or L. reuteri AMBV339 or their combination on the levels of SCFAs and related metabolites in the vagina . Comparisons will be made between the active groups and with placebo.

**Measure:** Short chain Fatty Acid (SCFA) levels in vagina

**Time Frame:** day 0 - day 28

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Women of reproductive age (appr. 18-45 years old)
* Women of self-reported good general health
* Living in Flanders and speaking Dutch
* Using a combination contraceptive pill (without stop week) during the study and at least three months before the study
* Subjects willing and able to give written informed consent and to understand, to participate and to comply with the clinical study requirements.

Exclusion Criteria:

* Current pregnancy or breastfeeding
* Antibiotic/antimycotic use during the last three months before the study
* Use of group B vitamin supplements or vitamin C during the study (record vitamin use via questionnaires)
* Ketogenic diet during the study and during the last two weeks before the study
* Oral and vaginal probiotic, prebiotic, and postbiotic and synbiotic supplementation during the study or recent use during the last two weeks before the study
* Vaginal douching during the study
* Presence of general infection
* Having a reproductive disorder or current vaginal infection or vaginal symptoms (VVC, BV, AV, etc.)
* Having a gastro-intestinal disorder or current GIT infections or gastrointestinal disorders (Crohn, IBS, IBD, etc.)
* Having any other medical condition that gives rise to exclusion from the study according to the responsible clinician/principal investigator of the study
* Participation in another clinical trial

**Healthy Volunteers:** True

**Maximum Age:** 45 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Sarah.Ahannach@uantwerpen.be

**Name:** Sarah Ahannach, Dr

**Phone:** +32 3 265 32 17

**Role:** CONTACT

**Contact 2:**

**Email:** mehdi.sadaghian@dsm-firmenich.com

**Name:** Mehdi Sadaghian, Dr

**Phone:** +41793074667

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Antwerp

**Contacts:**

***Contact 1:***

- **Email:** Sarah.Lebeer@uantwerpen.be

- **Name:** Sarah Lebeer, Dr

- **Phone:** +32 3 265 32 85

- **Role:** CONTACT

***Contact 2:***

- **Email:** Veronique.Verhoeven@uantwerpen.be

- **Name:** Veronique Verhoeven, Dr

- **Phone:** +32 3 265 25 18

- **Role:** CONTACT

**Country:** Belgium

**Facility:** Lab of Applied Microbiology and Biotechnology, University of Antwerp

**Status:** RECRUITING

**Zip:** 2020

#### Overall Officials

**Official 1:**

**Affiliation:** University of Antwerp Department of Family Medicine and Population Health

**Name:** Veronique Verhoeven, Dr

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** University of Antwerp Department of Bioscience Engineering

**Name:** Sarah Lebeer, Dr

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: HIGH

- As Found: Microbial Colonization

- ID: M6368

- Name: Communicable Diseases

- Relevance: HIGH

- As Found: Microbial Colonization

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003141

- Term: Communicable Diseases

- ID: D000007239

- Term: Infections

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Derm

- Name: Dermatologic Agents

- Abbrev: Ot

- Name: Other Dietary Supplements

- Abbrev: HB

- Name: Herbal and Botanical

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M17558

- Name: Vitamins

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M15085

- Name: Riboflavin

- Relevance: LOW

- As Found: Unknown

- ID: T355

- Name: Acidophilus

- Relevance: LOW

- As Found: Unknown

- ID: T120

- Name: Cola

- Relevance: LOW

- As Found: Unknown

- ID: T463

- Name: Riboflavin

- Relevance: LOW

- As Found: Unknown

- ID: T470

- Name: Vitamin B2

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
