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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Technical University of Denmark
Information provided by (Responsible Party):
Arne Astrup, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT01731366
First received: November 15, 2012
Last updated: September 1, 2014
Last verified: September 2014
  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
Primary Completion Date: February 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
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: NCT01731366

Locations
Denmark
Department of Human Nutrition, University of Copenhagen
Fredriksberg, Denmark, 1958
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: Arne Astrup, Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT01731366     History of Changes
Other Study ID Numbers: M206
Study First Received: November 15, 2012
Last Updated: September 1, 2014
Health Authority: Denmark: Danish Dataprotection Agency

Additional relevant MeSH terms:
Metabolic Diseases

ClinicalTrials.gov processed this record on September 22, 2014