The Effect of Gluten on Gut Microbiome and Metabolic Health. (3G)

This study has been completed.
Sponsor:
Collaborator:
Technical University of Denmark
Information provided by (Responsible Party):
Oluf Borbye Pedersen, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT01719913
First received: October 24, 2012
Last updated: December 4, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Metabolic Diseases
Injury of Gastrointestinal Tract
Other: High gluten
Other: Low gluten

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Gut, Grain and Greens (3G): The Effect of Gluten on Gut Microbiome and Metabolic Health.

Resource links provided by NLM:


Further study details as provided by University of Copenhagen:

Primary Outcome Measures:
  • Altered quantitative metagenomics at bacterial gene- and species levels. [ Time Frame: Up to 3 years. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean intestinal transit time [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    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.

  • Gastrointestinal permeability. [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    Lactulose/mannitol ratio in urine after four hours collection following oral intake of lactulose and mannitol.

  • Colonic fermentation [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    Breath hydrogen after intake of standardized breakfast (30,60,90,120,180 minutes)

  • Blood pressure and pulse. [ Time Frame: Up to 1 year. ] [ Designated as safety issue: No ]
    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.

  • Saliva microbial flora [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    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.

  • Nasal fluid [ Time Frame: Up to 3 years. ] [ Designated as safety issue: No ]
    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.

  • Appetite hormones [ Time Frame: Up to 3 years. ] [ Designated as safety issue: No ]
    Glucagon like peptide 1 and 2, Gastric inhibitory polypeptide, peptide YY and Ghrelin.

  • Celiac disease markers [ Time Frame: Up to 1 year. ] [ Designated as safety issue: No ]
    Levels of gliadin and Immunoglobulin A and G transglutaminase.

  • Blood lipid profile [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    Low density Lipoproteins, High density lipoproteins, Total Cholesterol, Very low density lipoproteins and Free fatty acids.

  • Bioimpedance [ Time Frame: Up to 1 year. ] [ Designated as safety issue: No ]
    Body composition (lean body mass and fat mass) is measured by bio-electrical impedance using multi frequency Quadscan.

  • Breath hydrogen. [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    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.

  • Insulin [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    Fasting insulin and post prandial at 30, 60, 90, 120 and 180 minutes after standardized meal.

  • Glucose [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    Fasting glucose and post prandial at 30, 60, 90, 120 and 180 minutes after standardized meal.

  • C-peptide [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    Fasting.

  • Inflammatory makers [ Time Frame: Up to 3 years. ] [ Designated as safety issue: No ]
    High sensitive C-reactive protein, Interleukin 1, 6 and 10, Lipopolysaccharide- binding protein, Tumor necrosis factor - alfa.

  • Anthropometric characteristics. [ Time Frame: Up to 1 year. ] [ Designated as safety issue: No ]
    Weight, height, sagittal height and waist circumference.


Other Outcome Measures:
  • 4 days precoded food diary. [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    Validated method for dietary registration, based on 2 week and 2 weekend days.

  • Gastrointestinal symptoms. [ Time Frame: Up to 2 years. ] [ Designated as safety issue: No ]
    Changes from baseline to after intervention in individual gastrointestinal symptoms by validated VAS-questionary.


Enrollment: 60
Study Start Date: October 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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)
Other: 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)
Other Name: Low gluten
Placebo Comparator: 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)
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)
Other Name: High gluten

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01719913

Locations
Denmark
The Novo Nordisk Foundation of Basic Metabolic Health, Section for Metabolic Genetics
Copenhagen, Denmark, 2100
Sponsors and Collaborators
University of Copenhagen
Technical University of Denmark
Investigators
Principal Investigator: Oluf B Pedersen, MD, DMSCi,Professor University of Copenhagen
  More Information

Additional Information:
No publications provided

Responsible Party: Oluf Borbye Pedersen, Scientific Director, professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT01719913     History of Changes
Other Study ID Numbers: NNF-CBMR 3861-34275
Study First Received: October 24, 2012
Last Updated: December 4, 2013
Health Authority: Denmark: Danish Dataprotection Agency

Additional relevant MeSH terms:
Metabolic Diseases
Wounds and Injuries

ClinicalTrials.gov processed this record on July 28, 2014