Clinical trial NCT03686293: A Personal Microbiome-dependent Glucose Response in Healthy Young Volunteers
Official title: A Personal Microbiome-dependent Glucose Response in Healthy Young Volunteers: a Meal Test Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Blood Glucose, High
Keywords: Glucose tolerance
Gut microbiota
Microbial richness
Gastric emptying
Metabolomics
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Technical University of Denmark
First posted: 2018-09-26
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Acute meal test
Primary purpose: BASIC_SCIENCE

Brief summary: Individuals eating identical meals present high variability in post-meal blood glucose response making comparisons challenging. This study evaluates in 40 healthy and fasted participants whether the postprandial glucose response upon a standardized breakfast is dependent on gut microbial richness. Gastric emptying rate, intestinal transit time, insulin, appetite hormones and measures of the intestinal microbiome and fermentation will also be analyzed in the context of postprandial glucose metabolism.

Detailed description: Elevated blood glucose levels constitute a major risk factor for pre-diabetic and diabetic patients. Postprandial glucose tests have been used for decades to monitor and compare glucose responses. Yet, individuals eating identical meals present high variability in post-meal blood glucose response making comparisons challenging. A recent landmark study showed that the inter-individual variation of postprandial glucose responses was associated with multiple person-specific factors including faecal microbiome factors. Gut microbial richness has for a long time been considered a hallmark of gut health and stability. Furthermore, microbial richness has been associated with colonic transit time, which together with the gastric emptying rate appear to be major determinants of the initial glycaemic response to carbohydrate-containing meals. Therefore, the aim of the study is to investigate whether postprandial glucose responses are associated with gut microbial richness, as well as secondary measures including gastric emptying rate, intestinal transit time and gut microbial composition and fermentation.

In an acute-meal study, 40 healthy fasted participants will consume a standardized breakfast including one tablet of paracetamol (for estimating gastric emptying rate) and 300 mL of juice.

Eligibility criteria: Inclusion Criteria:

* BMI \< 27
* Willing to eat lentils, tomatoes, spaghetti, bread, butter, strawberry jam, and drink juice
* Known ability to tolerate paracetamol
* No current use of medication (oral contraceptive pill and mild antidepressants is allowed)
* Did not take antibiotics, diarrhoea inhibitors and laxatives in the 6 previous months
* Willing to collect and deliver a faecal sample on the intervention day
* Willing to eat corn and fill out a self-reported corn-intestinal transit time questionnaire
* Willing to consume a paracetamol tablet (500 mg paracetamol)

Exclusion Criteria:

* Any condition that makes the project responsible researcher to doubt the feasibility of the volunteer's participation
* Pregnant or lactating women
* Suffering from irritable bowel disease (IBS), small intestine bacterial overgrowth (SIBO) or inflammatory bowel disease (IBD)
* Current chronic or infectious disease
* Current diagnosis of diabetes
* Blood donations within 3 months before participating in the current trial or participation in other scientific experiments
* Frequent intake of painkillers (paracetamol)

Primary outcomes:
measure: Postprandial plasma glucose at 60 min as a function of gut microbial richness
timeFrame: 60 min
Secondary outcomes:
measure: Fasting (baseline) plasma glucose as a function of gut microbial diversity/richness
timeFrame: 0 min
measure: Maximum plasma glucose concentration as a function of gut microbial diversity/richness
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Postprandial plasma glucose extremes as a function of gut microbial diversity/richness
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Time to plasma glucose maximum concentration as a function of gut microbial diversity/richness
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Postprandial plasma glucose AUC as a function of gut microbial richness/diversity
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Postprandial glucose 0-60 min as a function of gastric emptying
timeFrame: 0, 15, 30, 60 min
measure: Gastric emptying and postprandial glucose 0-120 min
timeFrame: 0, 15, 30, 60, 90 and 120 min
Other outcomes:
measure: Saliva microbiome
timeFrame: 0 min
measure: Fecal microbiome
timeFrame: 0 min
measure: Urine metabolome
timeFrame: 0, 0-150 min
measure: Fecal metabolome
timeFrame: 0 min
measure: Plasma metabolome
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Glucose metabolism
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Plasma Insulin
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Plasma short-chain fatty acids
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Lipid metabolism
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Glucagon like peptide 1 (GLP-1)
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Peptide tyrosine tyrosine (PYY)
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Ghrelin
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Gastric inhibitory polypeptide (GIP)
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Cholecystokinin (CCK)
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Gastric emptying
timeFrame: 0, 15, 30, 60, 90 and 120 min
measure: Postprandial breath exhalation
timeFrame: 0, 60, 150 min
measure: Feces short-chain fatty acids
timeFrame: 0 min
measure: Feces pH
timeFrame: 0 min
measure: Feces energy
timeFrame: 0 min
measure: Stool consistency
timeFrame: 0 min
measure: Intestinal transit time
timeFrame: Before intervention
measure: Defecation patterns
timeFrame: Before intervention
measure: Gastrointestinal symptoms
timeFrame: Before intervention
Locations:
city: Frederiksberg
country: Denmark
facility: Department of Nutrition, Exercise and Sports, University of Copenhagen
Study officials:
affiliation: University of Copenhagen
name: Lars O Dragsted, PhD
role: PRINCIPAL_INVESTIGATOR
References: