- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05130619
Human Auto-ethanol Formation and Acetate Signaling (HotFacets)
Human Auto-ethanol Formation and Acetate Signaling. Acute Effects of Alcohol on Short-chain Fatty Acid Dynamics and Energy Metabolism in Healthy Men and Women.
The HotFacets study is a randomized, controlled, cross-over meal study that investigates the acute effects of alcohol consumption on short-chain fatty acids dynamics, energy metabolism, and biomarkers.
Despite the negative health consequences of chronic alcohol abuse, observational and cohort studies associate moderate alcohol consumption with a 20-30 % lower risk of cardiovascular diseases (CVD) and Type 2 Diabetes Mellitus (T2DM), compared to abstainers. Based on the J-shaped relationship between alcohol intake and the risk of cardiometabolic diseases, ½-2 standard drinks/day can be considered as moderate alcohol consumption. The interpretation of the J-shaped relationship has been criticized mainly due to potential confounding from the selected reference group and uncontrolled lifestyle factors. Longer, well-designed randomized controlled trials are lacking to infer causality and to clarify the mechanism of action for the acute and chronic effects of moderate alcohol consumption on cardiometabolic health and energy homeostasis. However, some aspects of alcohol metabolism and biomarker validation could inform such a study.
HotFacets is set to generate insight into the effects of acute alcohol intake on SCFA dynamics in blood, urine, and faeces; into the dose-response relationship with REE, thermogenesis, substrate oxidation, and alcohol biomarkers; and to explore potential low levels of alcohol produced in the gut.
Study Overview
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Lars Ove Dragsted, PhD
- Phone Number: +45 35 33 26 94
- Email: ldra@nexs.ku.dk
Study Contact Backup
- Name: Catalina Cuparencu, Postdoc
- Email: cup@nexs.ku.dk
Study Locations
-
-
-
Frederiksberg, Denmark, 1958
- Recruiting
- Lars Ove Dragsted
-
Contact:
- Lars O Dragsted
- Phone Number: (+45) 35332694
- Email: Ldra@nexs.ku.dk
-
Principal Investigator:
- Lars O. Dragsted, Professor
-
-
Frederiksberg C
-
Copenhagen, Frederiksberg C, Denmark, 1958
- Recruiting
- Department of Nutrition, Exercise and Sports, University of Copenhagen
-
Contact:
- Catalina Cuparencu, PhD
- Email: cup@nexs.ku.dk
-
Contact:
- Lars O Dragsted, Professor
- Phone Number: +4535332694
- Email: ldra@nexs.ku.dk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Subjects will be recruited to the trial in two seasons. First, eight healthy men and post-menopausal women 50-75 years will be recruited for the pre-trial during autumn/winter 2021. Secondly, 16 healthy men and women with an age-range of 25-75 years will be recruited for the main trial during late spring/summer 2022.
Age-specific inclusion criteria for the pre-trial:
- Healthy men and healthy, post-menopausal women (12 consecutive months without menstrual period)
- Age: 50-75 years old
- BP ≤ 140/90 (systolic/diastolic)
- Plasma glucose <7 mmol/l
- BMI: 18.5-27 kg/m2
- Subjects with a good command of both written and verbal English
Age-specific inclusion criteria for the main-trial:
- Healthy men and women
- Age: 25-75 years old
- BP ≤ 140/90 (systolic/diastolic)
- Plasma glucose <7 mmol/l
- BMI: 18.5-27 kg/m2
Inclusion criteria for the pre- and main-trial:
- Willing to provide registration of compliance during the run-in period and follow-up periods
- Willing to avoid drinking alcohol for 2 weeks before the first test day and between test days
- Willing to stay in the respiration chamber the night before and after each test day
- Owning a smartphone
Exclusion Criteria:
- Alcohol naïve or has not consumed alcohol within the last year
Any history of alcohol or substance abuse or a high alcohol intake, defined as:
- An Alcohol Use Disorders Identification Test (AUDIT, appendix 1) score > 5 at screening
- Drinking on average >14 alcoholic beverages a week during the past 6 months
- Yale-Brown Obsessive Compulsive Scale-heavy drinking (Y-BOCS-hd, appendix 2) total score of ≥6 on questions 1, 2, and 3
- Intolerance or allergy to alcoholic beverages, juniper or citrus
- Diagnosed with any CVD event (MI, revascularization procedure or stroke) within the past six months
- Diagnosed with any known or past severe chronic disease including liver diseases (e.g., active hepatitis B and C infections, liver cirrhosis, hepatitis, cancer), T2DM, prediabetes, hypertension, severe psychiatric illness or frequent use of medication (except over-the-counter drugs or mild anti-depressants) or any other clinical condition that makes the subject ineligible according to the clinically responsible medical doctor (self-reported).
- Cancer - active malignant cancer or history of malignancy within the last 5 years (with exception of non-melanoma skin cancer).
Previous breast cancer diagnosis or at high risk of breast cancer defined as:
- Breast Cancer Risk Assessment Tool (BCRAT) risk score > 5 % (https://bcrisktool.cancer.gov/calculator.html)
- Close relatives with diagnosed breast cancer (mother, sister, daughter)
- A Patient Health Questionnaire (PHQ-9, appendix 3) ≥15 at screening or a positive response on question 9 (thoughts about suicide)
- Diagnosed with atrial fibrillation
- Hemoglobin (Hb) levels below 7.3 mmol/L for women and 8.3 mmol/L for men.
- Chronic use of any type of medication, except for mild antidepressants or contraceptives
- Any use of contraindicated medication for alcohol intake, such as disulfiram, dual antiplatelet therapy, metronidazole, warfarin or hormone replacement therapy
- Hypersensitive to plasters
- Use of any type of antibiotics within two month before the first test day
- Unintentional weight loss >20% during the last 6 months
- Any type of gastrointestinal problems or prior surgery expected to influence gut health and absorption.
- Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 or end-stage renal disease
- Liver function tests >2 times the upper limit of the normal range according to current limits at "sundhed.dk": alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT).
- Blood donations within the past three months before the recruitment
- Having no hair on the head (bald-headed)
- Current participation in another trial
- Not willing to sign the Informed consent form (ICF)
- Not willing to comply with the all the trial procedures including completion of the two-week run-in periods without drinking alcohol as well the two-week wash-out periods
- Unable or unwilling to follow the safety procedures related to Covid19
- Any other issue that makes the project responsible researcher doubt the eligibility of the volunteer
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment order A-.B-C-D
A: 5g ethanol-2-D3 mixed into 250ml water with added aromas of gin and lime juice B:10g ethanol-2-D3 mixed into 250ml water with added aromas of gin and lime juice C: 8g Triacetin mixed into 250ml water with added aromas of gin and lime juice D: 250ml water with added aromas of gin and lime juice
|
Crossover meal study
|
Experimental: Treatment order B-D-A-C
A: 5g ethanol-2-D3 mixed into 250ml water with added aromas of gin and lime juice B:10g ethanol-2-D3 mixed into 250ml water with added aromas of gin and lime juice C: 8g Triacetin mixed into 250ml water with added aromas of gin and lime juice D: 250ml water with added aromas of gin and lime juice
|
Crossover meal study
|
Experimental: Treatment order C-A-D-B
A: 5g ethanol-2-D3 mixed into 250ml water with added aromas of gin and lime juice B:10g ethanol-2-D3 mixed into 250ml water with added aromas of gin and lime juice C: 8g Triacetin mixed into 250ml water with added aromas of gin and lime juice D: 250ml water with added aromas of gin and lime juice
|
Crossover meal study
|
Experimental: Treatment order D-C-B-A
A: 5g ethanol-2-D3 mixed into 250ml water with added aromas of gin and lime juice B:10g ethanol-2-D3 mixed into 250ml water with added aromas of gin and lime juice C: 8g Triacetin mixed into 250ml water with added aromas of gin and lime juice D: 250ml water with added aromas of gin and lime juice
|
Crossover meal study
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
SCFA dynamics
Time Frame: 0-48 hours after intake
|
Difference in isotope labelled and unlabelled SCFA (mainly acetate, butyrate and propionate) concentration time course in feces, blood and urine following one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-48 hours after intake
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Resting energy expenditure
Time Frame: 0-3 hours after intake
|
Difference in resting energy expenditure, diet induced thermogenesis, and substrate oxidation following one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-3 hours after intake
|
substrate oxidation rate
Time Frame: 0-3 hours after intake
|
Difference in resting energy expenditure, diet induced thermogenesis, and substrate oxidation following one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-3 hours after intake
|
diet induced thermogenesis
Time Frame: 0-3 hours after intake
|
Difference in resting energy expenditure, diet induced thermogenesis, and substrate oxidation following one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-3 hours after intake
|
Biomarkers of alcohol intake in hair
Time Frame: 0-1 month after intake
|
Difference in alcohol biomarker levels of ethyl glucuronide, ethyl sulphate and fatty acid ethyl esters in hair following one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-1 month after intake
|
Biomarkers of alcohol intake in urine
Time Frame: 0-1 month after intake
|
Difference in alcohol biomarker levels in urine following one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-1 month after intake
|
Biomarkers of alcohol intake in red blood cells
Time Frame: 0-1 month after intake
|
Difference in alcohol biomarker levels in red blood cells following one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-1 month after intake
|
Biomarkers of alcohol intake in blood serum or plasma
Time Frame: 0-1 month after intake
|
Difference in alcohol biomarker levels in blood serum or plasma following one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-1 month after intake
|
Low-level endogenous alcohol production measured as biomarkers of ethanol exposure during strict abstention in a metabolic chamber
Time Frame: 0-48 hours after intake
|
Difference in low-level baseline alcohol production by the yeast and bacteria in the gut following one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-48 hours after intake
|
Isotope labelled metabolites
Time Frame: 0-48 hours after intake
|
Difference in metabolites of (non-radioactive) isotope-labelled ethanol compared with triacetin ingestion in blood, red blood cells, urine, faeces and hair; these metabolites are measured by liquid chromatography time-of-flight mass spectrometry as an increase in the third isotope peak for any molecular mass feature in the chromatogram.
|
0-48 hours after intake
|
Heart rate and blood pressure
Time Frame: 0-24 hours after intake
|
Difference in heart rate and BP including diurnal biphasic systolic and diastolic fluctuations measured through 24-hour ambulatory BP after one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-24 hours after intake
|
Alcohol levels in breath
Time Frame: 0-8 hours after intake
|
Difference in alcohol levels measured by an alcohol breath analyzer after one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-8 hours after intake
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Microbiome composition
Time Frame: 0-48 hours after intake
|
Differences in taxonomic composition (relative or absolute) of the gut microbiota when comparing one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-48 hours after intake
|
Microbiome functionality
Time Frame: 0-48 hours after intake
|
Differences in alcohol-producing functional composition of the oral and gut microbiota, when comparing samples collected before and after one unit of alcohol intake compared with half a unit, triacetin or water.
This fundtional composition is determined by the relative abundance of Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Clostridium subclusters IV and XIVa, Saccharomyces cerevisiae, Candida albicans and any other established alcohol-producing microbiota.
|
0-48 hours after intake
|
Faecal pH
Time Frame: 0-48 hours after intake
|
Differences in faecal pH, when comparing one unit of alcohol intake compared with half a unit, triacetin or water.
|
0-48 hours after intake
|
Metabolic fingerprints of urine
Time Frame: 0-48 hours after intake
|
Difference in metabolomes of urine when comparing samples taken up to 48 hours after one unit of alcohol intake compared with half a unit, triacetin or water.
The LC-MS and NMR metabolomes will be compared by PLS-DA to find discriminant patterns of metabolic features.
|
0-48 hours after intake
|
Metabolic fingerprints of plasma or serum
Time Frame: 0-48 hours after intake
|
Difference in metabolomes of blood serum/plasma when comparing samples collected after one unit of alcohol intake compared with half a unit, triacetin or water.
The LC-MS and NMR metabolomes will be compared by PLS-DA to find discriminant patterns of metabolic features.
|
0-48 hours after intake
|
Metabolic fingerprints of feces
Time Frame: 0-48 hours after intake
|
Difference in metabolomes of feces, when comparing samples collected after one unit of alcohol intake compared with half a unit, triacetin or water.
The LC-MS and NMR metabolomes will be compared by PLS-DA to find discriminant patterns of metabolic features.
|
0-48 hours after intake
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lars O Dragsted, PhD, University of Copenhagen
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- M240
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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