A Personal Microbiome-dependent Glucose Response in Healthy Young Volunteers

Blood Glucose, High Clinical Trial

— MIGLUCOSE  

Official title:

A Personal Microbiome-dependent Glucose Response in Healthy Young Volunteers: a Meal Test Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03686293
• Other study ID #: M233
• Status: Completed
• Phase: N/A
• Start date: October 12, 2018
• Est. completion date: December 11, 2018

Study information

• Verified date: December 2018
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 11, 2018
• Est. primary completion date: December 11, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Blood Glucose, High
• Hyperglycemia

Intervention

Other:
• Standardized breakfast
One tablet of paracetamol (500 mg) and a glass of water (150 mL) is consumed followed by a breakfast consisting of white bread, butter, jam, and juice (300 mL) and

Locations

Country	Name	City	State
Denmark	Department of Nutrition, Exercise and Sports, University of Copenhagen	Frederiksberg

Sponsors (2)

Lead Sponsor	Collaborator
University of Copenhagen	Technical University of Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Saliva microbiome	Determination of saliva microbiome composition at baseline	0 min
Other	Fecal microbiome	Determination of fecal microbiome composition at baseline	0 min
Other	Urine metabolome	Urine metabolome as determined by untargeted metabolic profiling by LC-QTOF of all urine samples collected before the meal and postprandially from 0-150 min	0, 0-150 min
Other	Fecal metabolome	Fecal metabolome as determined by untargeted metabolic profiling by LC-QTOF of ethanolic extracs from all baseline fecal samples collected before the intervention	0 min
Other	Plasma metabolome	Plasma metabolome as determined by untargeted metabolic profiling by LC-QTOF of ethanolic extracs from all fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Other	Glucose metabolism	Plasma glucose measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Other	Plasma Insulin	Plasma insulin measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Other	Plasma short-chain fatty acids	Plasma short-chain fatty acids measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Other	Lipid metabolism	Bile acids in blood (fasting and postprandially) and in feces (baseline)	0, 15, 30, 60, 90 and 120 min
Other	Glucagon like peptide 1 (GLP-1)	Plasma glucagon like peptide 1 (GLP-1) measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Other	Peptide tyrosine tyrosine (PYY)	PYY measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Other	Ghrelin	Ghrelin measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Other	Gastric inhibitory polypeptide (GIP)	GIP measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Other	Cholecystokinin (CCK)	CCK measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Other	Gastric emptying	Gastric emptying measured as postprandial paracetamol concentration profiles in blood	0, 15, 30, 60, 90 and 120 min
Other	Postprandial breath exhalation	Fasting and postprandial breath hydrogen/methane exhalation	0, 60, 150 min
Other	Feces short-chain fatty acids	Feces short-chain fatty acids measured in all fecal samples collected at baseline	0 min
Other	Feces pH	Feces pH measured in all fecal samples collected at baseline	0 min
Other	Feces energy	Feces energy measured in all fecal samples collected at baseline by bomb calorimetry	0 min
Other	Stool consistency	Consistency of stool sample collected at baseline assessed by the Bristol stool scale	0 min
Other	Intestinal transit time	Participants are instructed to observe the time it takes corn to travel through their gastrointestinal system five days prior to the intervention	Before intervention
Other	Defecation patterns	Average number of poops per day and average stool consistency as assessed by Bristol stool scale	Before intervention
Other	Gastrointestinal symptoms	Gastrointestinal symptoms measured on a 10 cm visual analog scale (VAS)	Before intervention
Primary	Postprandial plasma glucose at 60 min as a function of gut microbial richness	We test whether there is an inverse association between baseline fecal gut microbial richness and postprandial plasma glucose at 60 min after a standardised meal including 0.5 g paracetamol	60 min
Secondary	Fasting (baseline) plasma glucose as a function of gut microbial diversity/richness	We test whether there is an inverse association between fasting plasma glucose and baseline fecal gut microbial richness (cross-sectionally)	0 min
Secondary	Maximum plasma glucose concentration as a function of gut microbial diversity/richness	We test associations between gut microbial diversity/richness and maximum postprandial plasma glucose concentration [Cmax] after a standardised meal including 0.5 g paracetamol.	0, 15, 30, 60, 90 and 120 min
Secondary	Postprandial plasma glucose extremes as a function of gut microbial diversity/richness	We test associations between gut microbial diversity/richness and the difference from the postprandial plasma glucose peak to the glucose level after 60 min or at the postprandial minimum between 30-120 min after a standardised meal including 0.5 g paracetamol.	0, 15, 30, 60, 90 and 120 min
Secondary	Time to plasma glucose maximum concentration as a function of gut microbial diversity/richness	We test associations between gut microbial diversity/richness and the time to the postprandial plasma glucose maximum concentration [Cmax] after a standardised meal including 0.5 g paracetamol	0, 15, 30, 60, 90 and 120 min
Secondary	Postprandial plasma glucose AUC as a function of gut microbial richness/diversity	We test associations between gut microbial diversity/richness and AUC 0-120 min for plasma glucose after a standardised meal including 0.5 g paracetamol	0, 15, 30, 60, 90 and 120 min
Secondary	Postprandial glucose 0-60 min as a function of gastric emptying	We test associations between gastric emptying measured as AUC 0-60 min of postprandial paracetamol concentration profiles in blood and postprandial plasma glucose at 60 min during a standardised meal including 0.5 g paracetamol	0, 15, 30, 60 min
Secondary	Gastric emptying and postprandial glucose 0-120 min	We test associations between gastric emptying measured as AUC 0-120 min of postprandial paracetamol concentration profiles in blood and postprandial plasma glucose AUC 0-120 min during a standardised meal test with intake of 0.5 g paracetamol	0, 15, 30, 60, 90 and 120 min