Effect of Probiotic on Gut Microbiome and Bacterial Translocation in Healthy Asian Volunteers

NCT05083572 | Unknown Phase 4

• 1 other identifier: Vivomixx
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Dysbiosis of the gut microbiome has been recognized to underlie the pathogenesis of various gastrointestinal conditions. Probiotics are known to exert beneficial effects on gut health and have great potential for use as microbiome interventions for gastrointestinal and metabolic diseases. While it is widely known that probiotic bacteria favourably alter the intestinal microflora balance, their other mechanisms of action have not been systematically characterized. The ability of probiotics to modulate dysbiosis may lead to reduced levels of endotoxaemia and oxidative stress. In this study, the investigators propose to examine the effects of 4-week Vivomixx treatment on the gut microbiome and bacterial translocation in healthy Asian volunteers with and without colonic lavage or antibiotic treatment. The study will also examine the same outcome parameters 4 weeks upon cessation of the product. The findings derived from the study will provide valuable insights into the microbiota changes associated with colonic lavage or antibiotic treatment, and the use of probiotic (Vivomixx). This has important clinical implications in designing treatment strategies in clinical practice such as the use of Vivomixx as microbiome interventions with antibiotics which are known to induce Clostridium difficile-associated diarrhoea, as well as in the therapeutic management of various diseases associated with dysbiosis.

Conditions

Dysbiosis

Keywords

Gut microbiome; Probiotic; Bacterial translocation

Outcome Measures

Primary Outcomes (3)

• Microbiome profile using 16S rRNA sequencing

  Fresh stool samples will be collected for microbial DNA extraction at Days -14 and -7 (Group D), Day -1 (Groups A \& B), Days 1, 29 and 56 (All groups). Microbial DNA will be extracted from the stool samples and used for 16S rRNA sequencing. Bacterial species present in Vivomixx will be specifically examined.

  2 to 2.5 months

• Inflammatory cytokines using ELISA tests

  Inflammatory cytokines indicative of oxidative damage will be assayed using commercially available Elisa kits on serum samples obtained at Baseline and Day 29 (For Group C only).

  2 to 2.5 months

• Bacterial translocation using endotoxin assay

  Blood will be collected 2 hours post meal at baseline and Day 29 for endotoxin LAL assay using commercial kit (For Group C only).

  2 to 2.5 months

Secondary Outcomes (2)

• Peripheral blood lymphocyte phenotyping using flow cytometry

  2 to 2.5 months

• Short chain fatty acids using mass spectrometry

  2 to 2.5 months

Study Arms (4)

Group A (Lavage and Vivomixx)

EXPERIMENTAL

Colonic lavage, followed by Vivomixx treatment

Drug: Colonic lavage with polyethylene glycol; Dietary Supplement: Probiotic

Group B (Lavage and Placebo)

EXPERIMENTAL

Colonic lavage, followed by Placebo treatment

Drug: Colonic lavage with polyethylene glycol

Group C (Vivomixx)

EXPERIMENTAL

No colonic lavage, only Vivomixx treatment

Dietary Supplement: Probiotic

Group D (Rifaximin and Vivomixx)

EXPERIMENTAL

Rifaximin, followed by Vivomixx treatment

Dietary Supplement: Probiotic; Drug: Antibiotic

Interventions

Colonic lavage with polyethylene glycol DRUG

The subjects will orally consume a split dose of bowel preparation (PEG); 2 litres in the evening (Day -1) and another 2 litres the following morning (Day 1).

Also known as: PEG

Group A (Lavage and Vivomixx); Group B (Lavage and Placebo)

Probiotic DIETARY_SUPPLEMENT

The subjects will self-administer orally two capsules of Vivomixx with room temperature water (as heat may inactivate the live bacteria, rendering it less effective) twice daily for 28 days.

Also known as: Vivomixx

Group A (Lavage and Vivomixx); Group C (Vivomixx); Group D (Rifaximin and Vivomixx)

Antibiotic DRUG

The subjects will undergo pre-treatment to "cleanse" the gut by consuming orally one tablet of antibiotic rifaximin (200mg) daily for 14 days prior to the initiation of Vivomixx course.

Also known as: Rifaximin

Group D (Rifaximin and Vivomixx)

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed written informed consent,
• Aged between 21-65 years of age,
• Chinese, Malay or Indian ancestry through three generations,
• Body Weight ≥ 50kg, Body Mass Index (BMI) of 18.5 to 29.9 kg/m2, inclusive,
• Clinical laboratory assessment results within normal limits, unless the deviation is considered not clinically significant by the investigator,
• Regular stool every 1-2 days,
• Satisfactory medical assessment as assessed by physical examination, medical history, and normal laboratory values or minor variations that are not clinically significant,
• Ability to communicate with the investigator and to understand and comply with all requirements of study participation.
• Both male and female participants (with child-bearing potential) and their partners have to practise contraception throughout the duration of the study.

You may not qualify if:

• Any acute illness within 14 days of first dosing, unless otherwise approved by the PI,
• History or evidence of clinically significant hepatic, renal, cardiovascular, respiratory, gastrointestinal, immunosuppressive or metabolic disorders, any cancer types,
• Declare themselves positive for HIV or viral hepatitis (Hepatitis A, B, C),
• Treatment within the previous 3 months with antibiotics (subjects are to inform study staff should they be prescribed antibiotics during the course of the study)
• Treatment with any prescription or over-the-counter medications, complementary health products, or herbal supplements within 28 days of first dosing,
• Consumption of probiotics or lactobacillus-containing products e.g. Yakult, Vitagen or Yogurt within 4 weeks of first dosing unless approved by the PI,
• Abnormal biochemistry indicators, unless certified as not clinically significant,
• Poor peripheral venous access,
• Irregular bowel habits or complains of constipation problem,
• Pregnancy or lactation,
• Known allergic reactions to rifaximin, PEG or Vivomixx,
• History of drug/alcohol abuse,
• Involvement in the planning or conduct of this study.

Sponsors & Collaborators

• Changi General Hospital: lead

Study Sites (1)

Changi General Hospital

Singapore, 529889, Singapore

RECRUITING

Related Publications (2)

• Jalanka J, Salonen A, Salojarvi J, Ritari J, Immonen O, Marciani L, Gowland P, Hoad C, Garsed K, Lam C, Palva A, Spiller RC, de Vos WM. Effects of bowel cleansing on the intestinal microbiota. Gut. 2015 Oct;64(10):1562-8. doi: 10.1136/gutjnl-2014-307240. Epub 2014 Dec 19.

  PMID: 25527456 BACKGROUND

• Valentini L, Pinto A, Bourdel-Marchasson I, Ostan R, Brigidi P, Turroni S, Hrelia S, Hrelia P, Bereswill S, Fischer A, Leoncini E, Malaguti M, Blanc-Bisson C, Durrieu J, Spazzafumo L, Buccolini F, Pryen F, Donini LM, Franceschi C, Lochs H. Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - The "RISTOMED project": Randomized controlled trial in healthy older people. Clin Nutr. 2015 Aug;34(4):593-602. doi: 10.1016/j.clnu.2014.09.023. Epub 2014 Oct 8.

  PMID: 25453395 BACKGROUND

MeSH Terms

Conditions

Dysbiosis

Interventions

Polyethylene Glycols; Probiotics; Anti-Bacterial Agents; Rifaximin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethylene Glycols; Glycols; Alcohols; Organic Chemicals; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Tiing Leong Ang

  Changi General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seok Hwee Koo, PhD

CONTACT

+6568504929; seok_hwee_koo@cgh.com.sg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This will be a randomized controlled, partially-blinded study with four study arms to (i) examine the effect of Vivomixx on the gut microbiome with and without colonic lavage, (ii) with and without antibiotic treatment, (iii) compare the gut microbiome after natural recovery and with Vivomixx treatment following colonic lavage, and (iv) evaluate the efficacy of Vivomixx in reducing bacterial translocation and oxidative stress. The subjects will not be informed of the identity of the study product (Vivomixx or placebo) given. However, it is not possible to blind the subjects of the colonic lavage and rifaximin interventions. The investigators and outcomes assessors involved in the data analysis will be blinded to the study group allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief and Senior Consultant, Department of Gastroenterology and Hepatology

Study Record Dates

• First Submitted: October 3, 2021
• First Posted: October 19, 2021
• Study Start: March 10, 2021
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: March 22, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)