Identification of Biomarkers for Acute Intake of Beer and Alcohol and Acute Effects on Plasma and Insulin Response (METABEER)

• ClinicalTrials.gov Identifier: NCT02449577
• Recruitment Status: Completed
• First Posted: May 20, 2015
• Last Update Posted: May 20, 2015
• Sponsor: University of Copenhagen
• Collaborator: Carlsberg Breweries A/S
• Information provided by (Responsible Party): Professor Lars Ove Dragsted, University of Copenhagen

Tracking Information

• First Submitted Date: June 28, 2013
• First Posted Date: May 20, 2015
• Last Update Posted Date: May 20, 2015
• Study Start Date: May 2013
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 19, 2015)

Area under the curve (AUC) for glucose [ Time Frame: 0-180 minutes ]

Glucose is measured at 0, 45, 90, 120, and 180 min after the test meal and the area is determined by the trapezoid method.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: May 19, 2015)

• Area under the curve for insulin [ Time Frame: 0-180 min ]
  Insulin is measured at 0, 45, 90, 120, and 180 min after the test meal and the area is determined by the trapezoid method.
• Plasma concentration of fatty acid ethyl esters (FAEE) [ Time Frame: Change from 0-180min ]
  Change in FAEE from baseline to 180min by LC-MS/MS analysis of plasma.
• Blood level of ethanol [ Time Frame: 180 min ]
  The amount of ethanol is measured via a breath test using an alcoholmeter.
• Plasma beer metabolites (metabolic profiling with NMR and mass spectrometry). [ Time Frame: After the intervention ]
  Explorative marker to identify new beer intake-related metabolites in plasma.
• Urinary content of paraaminobenzoic acid (PABA) [ Time Frame: 24hour pooled urine from each volunteer ]
  Total PABA metabolites by colorimetric assay to account for completeness of urine collection.
• Urinary content of ethyl glucuronide (EtG) and ethyl sulphate (EtS) [ Time Frame: 0-24 hours ]
  EtG and EtS by quantitative LC-MS/MS
• Blood content of ethyl glucuronide (EtG) and ethyl sulphate (EtS) [ Time Frame: 0-180 min ]
  EtG and EtS are measured at 0, 45, 90, 120 and 180 minutes and the difference between treatments is determined by multivariate ANOVA followed (if significantly different) by t-tests for each time point.
• Urinary content of acetaldehyde (ethanal) [ Time Frame: 0 -24 hrs ]
  Ethanal is measured by a kit and compared between treatments.
• Urinary compounds of beer metabolites [ Time Frame: 0-24 hrs ]
  Metabolic profiling of urine by NMR and mass spectrometry.
• Blood pressure [ Time Frame: baseline and at time -30min on the last day of intervention. ]
  Measurement of supine systolic and diastolic blood pressure
• Body fat mass and body fat percentage [ Time Frame: baseline ]
  Measurement of body fat mass and fat percentage by bioimpedance
• Urinary creatinine [ Time Frame: 0-24hrs ]
  Creatinine is measured by standard clinical chemistry.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Identification of Biomarkers for Acute Intake of Beer and Alcohol and Acute Effects on Plasma and Insulin Response
• Official Title: Metabolomics in Beer Research: Identification of Biomarkers for Acute Intake of Beer and Alcohol in Individuals With a High or Low Habitual Intake, and Acute Effects on Plasma Glucose and Insulin Response Compared to Regular Soda
• Brief Summary: The objective of the study is to identify biomarkers for acute intake of beer and alcohol in individuals with a high or low habitual intake. Furthermore, we wish to identify compounds and metabolites in different types of beer and alcohol, which can serve as compliance markers for intake under the test conditions (blood tests and urine samples). We also wish to determine the acute effects of these beverages on plasma glucose and insulin response, compared to regular soda.

Detailed Description

The study is designed as a randomized, 4-way single-blinded cross-over intervention study. The participants are randomized individually to the order by which they shall receive 4 test meals. There will be implemented a standardized lunch which includes respectively 1) Light/alcohol-free (Tuborg Super Light 0,1% alcohol), 2) Regular lager (4,6% alcohol), 3) Strong beer(7,2% alcohol) and 4) a control drink without alcohol but with the same energy content (carbohydrate and protein) as the average of the other beverages ("sportsdrink"). Besides 330 ml of each test drink, each test meal consists of grilled cheese sandwiches (Tulip Food Company) and the amount of toast adjusted according to the type of drink served with each meal, so the content of macronutrients is the same in each meal.

The study includes 16-20 participants, randomized as to which order they will receive the 4 test meals with a washout period of at least 6 days in between test days. Upon arrival the test persons are asked to urinate (baseline sample), and at the 1st visit they are then weighed, height is measured and body composition (bioimpedance) is measured. After resting briefly, a baseline blood sample is taken and blood pressure is measured (1st and 4th visit). 45 minutes after start of the test meal the first postprandial blood sample is taken, and again after 45, 120 and 180 minutes. Urine is collected again at 0-90 min, 90-180 min and 3-24 hours after the test meal. Participants are provided with containers and equipment for this purpose, and must submit samples on an ongoing basis to the Dept. of Nutrition, Exercise and Sports.

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Investigator); Primary Purpose: Basic Science

Condition

• Alcohol Consumption
• Insulin Resistance

Intervention

• Other: Beverage sequence ABCD
  Participants receive test beverages in the randomised order ABCD
• Other: Beverage sequence CADB
  Participants receive test beverages in the randomised order CADB
• Other: Beverage sequence DACB
  Participants receive test beverages in the randomised order DACB
• Other: Beverage sequence CBAD
  Participants receive test beverages in the randomised order CBAD
• Other: Beverage sequence ABDC
  Participants receive test beverages in the randomised order ABDC
• Other: Beverage sequence DABC
  Participants receive test beverages in the randomised order DABC
• Other: Beverage sequence DCAB
  Participants receive test beverages in the randomised order DCAB
• Other: Beverage sequence DBCA
  Participants receive test beverages in the randomised order BDCA
• Other: Beverage sequence ADCB
  Participants receive test beverages in the randomised order ADCB
• Other: Beverage sequence BADC
  Participants receive test beverages in the randomised order BADC
• Other: Beverage sequence ACDB
  Participants receive test beverages in the randomised order ACDB

Study Arms

• Experimental: Beverage sequence ABCD
  Each participant randomized to this arm is exposed to 4 test meals in the order ABCD with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence ABCD
• Experimental: Beverage sequence CADB
  Each participant randomized to this arm is exposed to 4 test meals in the order CADB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence CADB
• Experimental: Beverage sequence DACB
  Each participant randomized to this arm is exposed to 4 test meals in the order DACB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence DACB
• Experimental: Beverage sequence CBAD
  Each participant randomized to this arm is exposed to 4 test meals in the order CBAD with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence CBAD
• Experimental: Beverage sequence ABDC
  Each participant randomized to this arm is exposed to 4 test meals in the order ABDC with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence ABDC
• Experimental: Beverage sequence DABC
  Each participant randomized to this arm is exposed to 4 test meals in the order DABC with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence DABC
• Experimental: Beverage sequence DCAB
  Each participant randomized to this arm is exposed to 4 test meals in the order DCAB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence DCAB
• Experimental: Beverage sequence DBCA
  Each participant randomized to this arm is exposed to 4 test meals in the order DBCA with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence DBCA
• Experimental: Beverage sequence ADCB
  Each participant randomized to this arm is exposed to 4 test meals in the order ADCB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence ADCB
• Experimental: Beverage sequence BADC
  Each participant randomized to this arm is exposed to 4 test meals in the order BADC with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence BADC
• Experimental: Beverage sequence ACDB
  Each participant randomized to this arm is exposed to 4 test meals in the order ACDB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)
  Intervention: Other: Beverage sequence ACDB

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 19, 2015): 19
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: June 2013
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy man or woman in the age group 18-60 years
• Likes and tolerates pasta, tomatoes and cheese, and is not a vegetarian or vegan, since meat (beef and pork) is included in the standardized dinner, breakfast and in the test meal
• Habitual alcohol intake (high: up to 7/14 units per week for women/men) or low: 0-2 units per week for both genders
• Tolerates alcohol

Exclusion Criteria:

• Systematic infections, psychiatric conditions and metabolic disease, and any clinical condition and other condition/situation, which according to the experimenter's assessment makes the person unfit to participate in the study
• Donation of a larger amount of blood (more than 24 ml) e.g. in connection with donation or other scientific research study, during the study and 3 months before start of the study
• Alcohol intake above the Danish Health and Medicines Authority's recommended 7 respective 14 drinks (units) per week for women and men
• Have or have had a drug addiction
• Allergy or intolerance to any of the tested drinks, or to any other foods included in the study. The participant will be specifically screened for possible alcohol allergy or intolerance
• Nursing, pregnancy or planned pregnancy.
• Not capable of complying with the procedures stipulated in the protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT02449577
• Other Study ID Numbers: M212
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Professor Lars Ove Dragsted, University of Copenhagen
• Study Sponsor: University of Copenhagen
• Collaborators: Carlsberg Breweries A/S

Investigators

• Principal Investigator: Lars O. Dragsted, Professor; Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark

• PRS Account: University of Copenhagen
• Verification Date: May 2015