Clinical trial NCT03140878: Defining the Normal Human Response to Probiotics
Official title: Defining the Normal Human Response to Probiotics and Developing an in Vitro System to Identify New Microbes With Probiotic Functions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Response to Probiotics
Lead sponsor: Chr Hansen
Sponsor class: INDUSTRY
Collaborators: name: University of Copenhagen
name: Herlev Hospital
First posted: 2017-05-04
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Genome-wide gene expression
timeFrame: 3 years
Secondary outcomes:
measure: 16S analysis of luminal fluid
timeFrame: 3 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Herlev hospital
Study officials:
References:
citation: 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.