Clinical trial NCT03384147: Metabolic Imprints of Alcoholic Beverages
Official title: Metabolic Imprints of Alcoholic Beverages
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Side Effects of Drugs and Substances
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Carlsberg Foundation
First posted: 2017-12-27
Enrollment: 26
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study was conducted in two predefined groups of volunteers, 1) daily alcohol users of maximally one (females) or two (males) drinks per day, and 2) occasional drinkers (0-2 drinks per week). Group 1 was asked to abstain from alcohol for 3 weeks, then to resume drinking 1-2 drinks daily for the next three weeks. Group 2 was asked to drink 1-2 drinks daily for 3 weeks and then to abstain for the following 3 weeks. During the alcohol intake period both groups were randomized to sequences of 4-5 days with red wine, white wine, lager beer, apple cider, or spirits. The primary endpoint was an effect of alcohol on dihydroepiandrosterone sulphate excretion in urine. Biomarkers of alcohol intake and alcohol-induced metabolic change, physical activity, or well-being were secondary outcomes.
Primary purpose: BASIC_SCIENCE

Brief summary: Metabolic imprints of five different types of alcohol will be investigated in two study groups.

The study will be an assessor-blinded, parallel dietary trial (crossover design).

The project aims to identify the chemical nature and kinetics of metabolite changes related to alcohol, hops, grapes and other beverage constituents as well as the brewing processes.

Detailed description: Metabolic imprints of five different types of alcohol will be investigated in two study groups of 15 participants in each with equal distribution of gender, occasional (0-2 u/week) and habitual drinkers (\>2 u/week), respectively.

The intervention is divided into two periods: abstaining and drinking period. Occasional drinkers begin the abstaining intervention and habitual drinkers begin the drinking intervention, and cross-over after 3 weeks.

In the drinking period women consume 1 unit/day and men 2 units/day.

Study participants will consume five different types of alcohol; beer, cider, white wine, red wine and spirits. The sequence of alcohol consumption in the drinking period is randomized by 'random number allocation'.

Study participants are asked to collect 24h urine samples three days in beginning of each intervention and one day in the end of last intervention. The remaining days of the trial they are asked to make a urine spot test each morning at home. Beside urine samples, they are to give blood samples on each trial day and at screening (6 times). Overnight-fasting blood samples are drawn at day 0, 1 and 21, 22 and 42 of the six week intervention and one at screening before intervention.

Furthermore, participants receive kits to provide a dry blood sampling the following three days after trial days in situ. There will also be taken blood pressure and questionnaire handouts. A voluntary hair sample will be taken at Baseline (day 0) and final day of intervention (day 42).

From these samples the following will be determined:

1. dehydroepiandrosterone sulphate (DHEAS) and related (steroid) hormones and metabolites (primary hypothesis is a sustained increase in DHEAS following alcohol intake)
2. cresol, cresol sulphate, indoxyl sulphate and indole acetic acid (human microbial co-metabolites)
3. humulone-derived conjugates and several analogues and unidentified metabolites from the intake of raw materials from beverage production, including hops, malt, cider apples and grapes etc. (by explorative methods)
4. malt- or brewing-related unidentified metabolites (by explorative methods)
5. additional markers of wine and strong liquor intake (by explorative methods)
6. investigating the use of sampling urine and blood on filter papers and the feasibility of collecting small hair samples
7. investigating metabolic markers in relation to blood pressure, heart rate, physical activity, blood lipids, fibrinogen, adiponectin, and psychosocial well-being etc. after 3 weeks light to moderate alcohol intake or abstaining.
8. metabolic profiling of urine, blood and hair to explore contrasts between periods of drinking and abstaining or periods with specific alcoholic beverages.

Eligibility criteria: Inclusion Criteria:

* 20 years of age
* No intolerance of alcohol
* Experience with alcohol
* Able to use smartphone or tablet

Exclusion Criteria:

* Serious chronic health conditions or psychiatric diseases
* Chronic intake of medicine (beside birth control and SSRI)
* Alcohol and/or drug abuse assessed AUDIT score \>4 (AUDIT = Alcohol Use Disorders Identification Test).
* Blood samples/donations during trial and 3 months prior
* Liver dysfunction
* High risk of breast cancer assessed by BCRAT score (BCRAT = The Breast Cancer Risk Assessment Tool)
* Pregnancy or lactating

Primary outcomes:
measure: DHEAS
timeFrame: 3 weeks
Secondary outcomes:
measure: Markers of alcohol intake
timeFrame: 3 weeks
measure: Human microbial co-metabolites
timeFrame: 3 weeks
measure: Markers of intake of raw materials from the beverage productions
timeFrame: 1 day
measure: Metabolites from outcomes 1-4 measured in dry urine spots
timeFrame: 1 day
measure: Metabolites from outcomes 1-4 measured in dry blood samples
timeFrame: 1 day
measure: Metabolites from outcomes 1-4 measured in a hair sample
timeFrame: 3 weeks (1 day)
measure: Blood pressure
timeFrame: 1d - 3 weeks
measure: Physical activity monitoring
timeFrame: 1d - 3weeks
measure: Blood lipids
timeFrame: 3 weeks
measure: Fibrinogen
timeFrame: 3 weeks
measure: Adiponectin
timeFrame: 3 weeks
measure: Psychosocial well-being
timeFrame: 3 weeks
Other outcomes:
measure: Discriminant metabolic profiles
timeFrame: 3 weeks
measure: Discriminant metabolic profiles
timeFrame: 4-5 days
Locations:
city: Copenhagen
country: Denmark
facility: Department of Nutrition, Exercise and Sports, University of Copenhagen
state: Frederiksberg C
Study officials:
affiliation: University of Copenhagen
name: Lars O Dragsted, PhD
role: PRINCIPAL_INVESTIGATOR
References: