The Effect of Whole Grain on Gut Microbiome and Metabolic Health (3G)

This study is currently recruiting participants.
Verified January 2013 by University of Copenhagen
Sponsor:
Collaborator:
Technical University of Denmark
Information provided by (Responsible Party):
AAstrup, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT01731366
First received: November 15, 2012
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

Objective: To identify how specific changes of the whole grain 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 intervention periods, separated by a 6-week wash-out period. A total of 60 participants will be included.

Intervention: low vs. high whole grain intake.


Condition Intervention
Metabolic Disease
Injury of Gastrointestinal Tract
Other: Whole grain
Other: Refined grain

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Official Title: Gut, Grain and Greens (3G): The Effect of Wholegrain on Gut Microbiome and Metabolic Health

Resource links provided by NLM:


Further study details as provided by University of Copenhagen:

Primary Outcome Measures:
  • HOMA-IR [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Homeostasis Model Assessment of fasting Insulin Resistance (HOMA-IR: glucose (mmol/l( x insulin (pmol/l)/22.5)

  • Metagenomic profile [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Altered quantitative metagenomics at bacterial gene- and species levels, which is a non-specific outcome, but included as the main hypothesis of the project is to test if HOMA-IR is affected via changes in the gut microbiome.


Secondary Outcome Measures:
  • Mean intestinal transit time [ Time Frame: At the end of the intervention periods ] [ 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, Lactulose/ mannitol ratio [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    5 hours urine collection following intake of lactulose and mannitol

  • Colonic fermentation [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Measurement of breath hydrogen excretion (at before and 30, 60, 90, 120, 150, 180 after intake of standard breakfast) and plasma short-chain fatty acids (fasting and 30, 60, 120, 180 minutes after standard breakfast)

  • Saliva microbial flora [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Determination of fasting microbial composition of flora.

  • Blood pressure [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Measurement of supine systolic and diastolic blood pressure (3 times)

  • Appetite hormones [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Determination of different appetite hormones in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)

  • Blood lipid profile [ Time Frame: At the end of the interventions periods ] [ Designated as safety issue: No ]
    Measurement of different blood lipids in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)

  • Body composition [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Measurement of body fat mass and percentage via bio-impedance

  • Subjective appetite sensation [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Assessment of subjective appetite sensation via visual analogue scales

  • Energy intake [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Assessment of energy intake at an ad libitum meal 3 hours after a standard breakfast

  • Ex vivo cytokine production [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Production of cytokines (such as IL-1beta, IL-6) in stimulated whole blood cultures.

  • Gene expression [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Assessed by mRNA qPCR in whole blood and cells from whole blood stimulation. Main focus is put on genes involved in immune function and metabolic regulation.

  • Immune cell profiling [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Assessed by flow cytometry of whole blood.

  • Immune markers [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Fasting plasma cytokines, hsCRP, and LPS/LPS-BP

  • Blood immune cell content [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Assessed by hematological cell counts

  • Markers og glucose hemostasis [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Measurement of plasma concentrations of Insulin, Proinsulin and HbA1c

  • Markers of one-carbon metabolism [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Assessed by plasma homocystein, SAM/SAH and betain

  • Plasma adipokines [ Time Frame: December 2015 ] [ Designated as safety issue: No ]
    Leptin and adiponectin


Other Outcome Measures:
  • 4-days precoded food diary [ Time Frame: December 2014 ] [ Designated as safety issue: No ]
    Assessment of dietary intake via food frequency questionnaire as a measure of compliance

  • n-3 fatty acid status [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Assessed as DHA percentage in a whole blood fatty acid analysis. Included as a potential effect modificator in relation to immune function and metabolic outcomes.

  • Alkyresorcinol [ Time Frame: At the end of the intervention periods ] [ Designated as safety issue: No ]
    Measured in plasma as a marker of compliance to the whole grain intervention.


Estimated Enrollment: 60
Study Start Date: August 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Refined grain
Refined grain diet: Participants consume less than 10 g of whole grain per day (corresponds to the whole grain intake below the 10th percentile of the population)
Other: Refined grain
Refined grain diet: Participants consume less than 10 g of whole grain per day (corresponds to the whole grain intake below the 10th percentile of the population)
Active Comparator: Whole grain
Whole grain diet: Participants consume more than 75g of whole grain per day (corresponds to the whole grain intake of the 90th percentile of the population)
Other: Whole grain
Whole grain diet: Participants consume more than 75g of whole grain per day (corresponds to the whole grain intake of the 90th percentile of the population)

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 diet rich in whole grain in the active treatment period and a refined grain diet during the control period.

Measurements: Insulin sensitivity will be assessed by means of a meal challenge test and by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) which is the primary outcome of this study. Secondary outcomes include metabolic and inflammatory markers, appetite hormones, transit time, and GM composition. Furthermore, selected control measures are included; 4-day food records and a study intervention diary.

  Eligibility

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

Inclusion Criteria:

  • Body mass index (BMI): 25 - 35 kg/m2
  • No medical prescribed diet
  • Weight stable
  • No blood donation during the study
  • Intense sporting activities less than 10h/ week
  • Alcohol consumption less than 14 units/ week (female) and 21 units/ week (male)
  • Signed written consent

Exclusion Criteria:

  • Pharmacological treatment; hypertension, 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
  • Intake of vitamin, mineral, or pre- or probiotic supplements for 1 month prior to study start
  • Blood hemoglobin < 7.0 mmol/l
  • Blood donation within 1 month prior to study start
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01731366

Locations
Denmark
Department of Human Nutrition, University of Copenhagen Recruiting
Fredriksberg, Denmark, 1958
Contact: Lotte Lauritzen, Associate professor    +45 35332508    ll@life.ku.dk   
Principal Investigator: Lotte Lauritzen, Associate professor         
Sponsors and Collaborators
University of Copenhagen
Technical University of Denmark
Investigators
Principal Investigator: Lotte Lauritzen, Associate professor University of Copenhagen
  More Information

Additional Information:
No publications provided

Responsible Party: AAstrup, Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT01731366     History of Changes
Other Study ID Numbers: M206
Study First Received: November 15, 2012
Last Updated: January 16, 2013
Health Authority: Denmark: Danish Dataprotection Agency

Additional relevant MeSH terms:
Metabolic Diseases
Wounds and Injuries

ClinicalTrials.gov processed this record on April 21, 2014