The Effect of Gluten on Gut Microbiome and Metabolic Health.

Metabolic Diseases Clinical Trial

— 3G  

Official title:

Gut, Grain and Greens (3G): The Effect of Gluten on Gut Microbiome and Metabolic Health.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01719913
• Other study ID #: NNF-CBMR 3861-34275
• Status: Completed
• Phase: N/A
• First received: October 24, 2012
• Last updated: December 4, 2013
• Start date: October 2012
• Est. completion date: November 2013

Study information

• Verified date: December 2013
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical Trial Summary

Objective: To identify how specific changes of the gluten content in the diet affect the host-gut microbiome interactions with implications for metabolic health.

Design: A randomized, controlled, single-blinded, cross-over intervention trial consisting of two 8-week interventions periods, separated by a 6-week wash-out period. A total number of 60 participants will be included.

Intervention: low vs high gluten intake.

Description:

The study is designed as a randomized, controlled, single-blinded, cross-over intervention trial consisting of two 8-week interventions periods, separated by a 6-week wash-out period. A total number of 60 participants will be included. Participants consume, in randomized order, a gluten-poor diet (<5 g/d) in the active treatment period and a gluten-rich diet (>25 g/d) during the control period.

Measurements: Altered quantitative metagenomics at bacterial gene- and species levels is the primary outcome of this study. Secondary outcomes include metabolic and inflammatory markers, circulating appetite hormone levels,serum metabolomics, gastrointestinal transit time and intestinal permeability. Furthermore, selected control measures are included; 4-day food records and a study intervention dietary records.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria, compulsory:

• Body mass index (BMI): 25 - 35 kg/m2 OR

• Abdominal obesity: waist circumference: men: = 94cm; women: = 80cm

• No medically prescribed diet

• Weight stable

• Intense sporting activities less than 10 h/week

• Alcohol consumption less than 14 units/week (female) and 21 units/week (male)

• Signed informed consent

Inclusion criteria, minimum one of the following:

• Fasting plasma glucose from 6.1 mmol/l to 6.9 mmol/l

• Reduced high density lipoprotein (HDL) cholesterol; HDL = 1.03 mmol/L for men and = 1.29 mmol/L for women

• Increased triglyceride (TG) > 1.3 mmol/L

• Systolic blood pressure > 130 mmHg

Exclusion Criteria:

• Pharmacological treatment; diabetes and blood lipid regulation

• Lactating (or lactating, 6 weeks ago), pregnant (or pregnant, 3 months ago) or wish to become pregnant during the study

• Participation in another biomedical trial 1 month prior to study start

• Diagnosed with any form of diabetes, celiac disease or chronic pancreatitis

• Reported chronic gastrointestinal disorders

• Antibiotic treatment for 3 month prior to study start

• Blood hemoglobin < 7.0 mmol/l

• Blood donation within 1 month prior to study start

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Injury of Gastrointestinal Tract
• Metabolic Diseases

Intervention

Other:
• High gluten
Refined grain/ gluten rich diet : Participants consume more than 25g of gluten per day (estimated to correspond to a gluten intake around the 90th percentile in the population)
• Low gluten
Poor gluten diet: Participants consume less than 5g gluten per day (estimated to correspond to a gluten intake below the 10th percentile in the population)

Locations

Country	Name	City	State
Denmark	The Novo Nordisk Foundation of Basic Metabolic Health, Section for Metabolic Genetics	Copenhagen

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	4 days precoded food diary.	Validated method for dietary registration, based on 2 week and 2 weekend days.	Up to 2 years.	No
Other	Gastrointestinal symptoms.	Changes from baseline to after intervention in individual gastrointestinal symptoms by validated VAS-questionary.	Up to 2 years.	No
Primary	Altered quantitative metagenomics at bacterial gene- and species levels.	Feces samples are collected according to standard operation procedures for subsequent standardized microbial DNA extraction. Microbial DNA will be subjected to sequencing, microbial gene analyses, taxonomy analyses including enterotypes known species and unknown meta-species and functional annotation.	Up to 3 years.	No
Secondary	Mean intestinal transit time	Participants are instructed in swallowing capsules containing different small non-invasive and non-absorbable plastic pellets for 6 consecutive days. On the seventh day they are having an X-ray of the abdomen taken.	Up to 2 years.	No
Secondary	Gastrointestinal permeability.	Lactulose/mannitol ratio in urine after four hours collection following oral intake of lactulose and mannitol.	Up to 2 years.	No
Secondary	Colonic fermentation	Breath hydrogen after intake of standardized breakfast (30,60,90,120,180 minutes)	Up to 2 years.	No
Secondary	Blood pressure and pulse.	Systolic and diastolic blood pressure and heart beat rate are measured after 10 min of rest according to current standard operational procedure with an automatic blood pressure meter. Participants are instructed not to talk during the measurements.	Up to 1 year.	No
Secondary	Saliva microbial flora	Saliva is collected after the participants have taken a small piece of paraffin in their mouth and have chewed until the paraffin has turned into one coherent mass (approximately one minute). Participants are swallowing the produced saliva for that minute. After this, and for the next 3 minutes, saliva is collected in a cup and handed over to the study personnel. Saliva is stored at minus 80 degrees for later studies of saliva microbial flora and saliva biochemistry.	Up to 2 years.	No
Secondary	Nasal fluid	Nasal fluid is collected by a non-invasive methodology for in vivo measurement of an array of immunological signalling molecules in the nasal airway lining. The method is based on a standardized collection of mucosal airway fluid from both nostrils onto small sheets of filter papers with efficient absorption properties. The technique is highly reproducible, and used for measuring immunological mediators representing the immediate response ability of the mucosal immune system.	Up to 3 years.	No
Secondary	Appetite hormones	Glucagon like peptide 1 and 2, Gastric inhibitory polypeptide, peptide YY and Ghrelin.	Up to 3 years.	No
Secondary	Celiac disease markers	Levels of gliadin and Immunoglobulin A and G transglutaminase.	Up to 1 year.	No
Secondary	Blood lipid profile	Low density Lipoproteins, High density lipoproteins, Total Cholesterol, Very low density lipoproteins and Free fatty acids.	Up to 2 years.	No
Secondary	Bioimpedance	Body composition (lean body mass and fat mass) is measured by bio-electrical impedance using multi frequency Quadscan.	Up to 1 year.	No
Secondary	Breath hydrogen.	Breath hydrogen measurements are done before the intake of the standardized breakfast (at 30, 60, 90, 120, 180 minutes), as an indicator of colonic fermentation.	Up to 2 years.	No
Secondary	Insulin	Fasting insulin and post prandial at 30, 60, 90, 120 and 180 minutes after standardized meal.	Up to 2 years.	No
Secondary	Glucose	Fasting glucose and post prandial at 30, 60, 90, 120 and 180 minutes after standardized meal.	Up to 2 years.	No
Secondary	C-peptide	Fasting.	Up to 2 years.	No
Secondary	Inflammatory makers	High sensitive C-reactive protein, Interleukin 1, 6 and 10, Lipopolysaccharide- binding protein, Tumor necrosis factor - alfa.	Up to 3 years.	No
Secondary	Anthropometric characteristics.	Weight, height, sagittal height and waist circumference.	Up to 1 year.	No

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