Defining the Normal Human Response to Probiotics

Defining the Normal Human Response to Probiotics and Developing an in Vitro System to Identify New Microbes With Probiotic Functions

The study is a mono-center, randomized, semi-blinded, placebo-controlled, cross-over, proof-of principle study in healthy volunteers. The study will determine the probiotic effect of LGG on intestinal tissue and intestinal cells

Study Overview

• Status: Completed
• Conditions: Healthy Response to Probiotics
• Intervention / Treatment: Dietary supplement: LGG; Dietary supplement: Placebo

Detailed Description

The study includes 3 visits. The first visit serves to check inclusion/exclusion criteria/complete questionnaire/give information about the study and receive consent. At visit 2 and 3 the included individuals will drink a placebo blend or a drink containing Lactobacillus rhamnosus GG (LGG®) and they will subsequently be biopsied from the upper intestine during endoscopy while under nurse administered propofol sedation (NAPS). There will be four weeks between visit 2 and 3.

At visit 2 and 3, biopsies will be taken from duodenum and jejunum, and luminal fluids will be collected, and one blood sample will be collected.

The down stream analysis will include a combination of gene expression analysis, microbiome analysis and classification of the individuals based on analysis of blood samples.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy men or women
2. No medication
3. Age between 18 and 35 years
4. BMI below 30
5. Provided voluntary written informed consent

Exclusion Criteria:

1. All clinical diagnoses and disorders requiring medicine
2. Patient diagnosed with inflammatory bowel disease such as ulcerative colitis and Crohn's disease, colorectal cancer or suffering from irritable bowel syndrome.
3. Pregnant and women who are breast-feeding
4. Patient with known blood clothing disorders
5. Patients with clinical psychiatric diagnoses (including dementia)
6. Individuals who have undergone abdominal surgery, which might have effect on the GI function, except appendectomy and cholecystectomy
7. Individuals with high blood pressure (≥140 mmHg /90 mmHg)
8. Systemic use of antibiotics or steroids or antimicrobial medication in the last 4 months
9. Daily usage of NSAID in the last 2 months or incidental use in the last 2 weeks prior to screening
10. Usage of medications, except oral contraceptives, during the 14 days prior to screening
11. Lactose intolerance
12. Participation in other clinical trials in the past three months
13. Regular use of probiotics in the last 6 weeks
14. Smoking
15. Planned changes to current diet or exercise regime
16. Use of laxatives, anti-diarrheals, anti-cholinergics within last 4 weeks prior to screening
17. Use of immunosuppressant drugs within last 4 weeks prior to screening
18. Ulcer or malignancy in the intestine which is discovered during second visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LGG; Lactobacillus rhamnosous (LGG) 450 billion CFU dissolved in water	Dietary supplement: LGG; LGG is dissolved in water and consumed at one occasion (either at visit 2 or 3)
Placebo Comparator: Placebo; The placebo product is the same vegetable capsule as the experimental product, identical in composition, taste and appearance but without probiotics	Dietary supplement: Placebo; Placebo is dissolved in water and consumed at one occasion (either at visit 2 or 3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genome-wide gene expression	The effect of LGG on genome-wide gene expression in intestinal tissue and cells	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
16S analysis of luminal fluid	3 years

Collaborators and Investigators

• Sponsor: Chr Hansen
• Collaborators: University of Copenhagen; Herlev Hospital

Publications and helpful links

General Publications

• Bornholdt J, Broholm C, Chen Y, Rago A, Sloth S, Hendel J, Melsaether C, Muller CV, Juul Nielsen M, Strickertsson J, Engelholm L, Vitting-Seerup K, Jensen KB, Baker A, Sandelin A. Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial. Gut Microbes. 2020 Nov 9;12(1):1-14. doi: 10.1080/19490976.2020.1854639.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2017
• Primary Completion (Actual): June 11, 2017
• Study Completion (Actual): June 11, 2017

Study Registration Dates

• First Submitted: May 1, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 4, 2017

Study Record Updates

• Last Update Posted (Actual): April 23, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: HND-GI-024; H-17002470 (Registry Identifier: Regional ethical committee Denmark)

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