HealthyHotFacetsNCT05130619
Human Auto-ethanol Formation and Acetate Signaling
A study testing Ethanol in people with Healthy, run by University of Copenhagen at 2 sites in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 25 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Ethanol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesDenmark
- Study dates
- 10 Nov 2021to Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 30Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Catalina Cuparencu, Postdoc contact
Denmark2 sites, 2 recruiting
- Recruiting
Department of Nutrition, Exercise and Sports, University of Copenhagen
Copenhagen, Frederiksberg C, 1958
Lars O Dragsted, Professor, +4535332694, ldra@nexs.ku.dk
Catalina Cuparencu, PhD, cup@nexs.ku.dk
- Recruiting
Lars Ove Dragsted
Frederiksberg, 1958
Lars O Dragsted, (+45) 35332694, Ldra@nexs.ku.dk
Lars O. Dragsted, Professor
About this study
Official title: 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.
Read the detailed description
A randomized, controlled, four times cross-over, single-blinded, meal study with 24 healthy fasting subjects will be conducted with a) placebo (water), b) a metabolic acetate generator (triacetin), and c) a half or d) one unit of isotope labelled ethanol, provided in a randomized order. Volunteers will be confined in a metabolic chamber overnight before each test drink (in 250mL water with lemon and juniper taste) and energy production and expenditure will be measured initially using seven ventilated hood measurements. After the test drinks and ventilated hood measurements an ad libitum lunch will be served before the participants will be admitted to the metabolic chamber, where metabolic measurements will be continued until the following day. Participants will go through a 2-week run-in period before each test drink and a 2-week wash out period afterwards, both with alcohol abstention. From two days before the test day in each period until one day after the test days, standardized foods will be provided. Anthropometrics, DXA, heart rate, blood pressure and all movements will be recorded before and/or during the test days. Before, during, and after the test day repeated biological samples (i.e., urine, blood, feces, hair) will be collected. The study will be divided into a pre-trial (8 subjects, 50-75y) and a main trial (16 subjects, 25-75y).
- Conditions
- Healthy
- Being tested
- Ethanol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EthanolDietary supplement
Crossover meal study
| Study group | Role | What they receive |
|---|---|---|
| Treatment order A-.B-C-D | Experimental | 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 Receives: Dietary Supplement: Ethanol |
| Treatment order B-D-A-C | Experimental | 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 Receives: Dietary Supplement: Ethanol |
| Treatment order C-A-D-B | Experimental | 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 Receives: Dietary Supplement: Ethanol |
| Treatment order D-C-B-A | Experimental | 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 Receives: Dietary Supplement: Ethanol |
What is being measured
The primary outcome is the main question the study is designed to answer.
SCFA dynamics
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.
Measured: 0-48 hours after intake
Secondary outcomes (11)
Resting energy expenditure
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.
Measured: 0-3 hours after intake
substrate oxidation rate
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.
Measured: 0-3 hours after intake
diet induced thermogenesis
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.
Measured: 0-3 hours after intake
Biomarkers of alcohol intake in hair
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.
Measured: 0-1 month after intake
Biomarkers of alcohol intake in urine
Difference in alcohol biomarker levels in urine following one unit of alcohol intake compared with half a unit, triacetin or water.
Measured: 0-1 month after intake
Biomarkers of alcohol intake in red blood cells
Difference in alcohol biomarker levels in red blood cells following one unit of alcohol intake compared with half a unit, triacetin or water.
Measured: 0-1 month after intake
Biomarkers of alcohol intake in blood serum or plasma
Difference in alcohol biomarker levels in blood serum or plasma following one unit of alcohol intake compared with half a unit, triacetin or water.
Measured: 0-1 month after intake
Low-level endogenous alcohol production measured as biomarkers of ethanol exposure during strict abstention in a metabolic chamber
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.
Measured: 0-48 hours after intake
Isotope labelled metabolites
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.
Measured: 0-48 hours after intake
Heart rate and blood pressure
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.
Measured: 0-24 hours after intake
Alcohol levels in breath
Difference in alcohol levels measured by an alcohol breath analyzer after one unit of alcohol intake compared with half a unit, triacetin or water.
Measured: 0-8 hours after intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2021
- Study start10 Nov 2021
- Primary completion1 Apr 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Lars Ove Dragsted, University of Copenhagen
- Investigators
- Lars O Dragsted, PhD, Principal investigator, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05130619
- Sponsor's protocol ID
- M240
- Acronym
- HotFacets
- Status last verified
- Nov 2023
- First submitted
- 14 Oct 2021
- Last updated
- 30 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Samples are to be anonymized before being shared with other researchers if the case.
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT05130619
- Acronym / sponsor ID
- HotFacets / M240
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Study start
- 10 Nov 2021 (actual)
- Primary completion
- 1 Apr 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 23 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A randomized, controlled, four times cross-over, single-blinded, meal study with 24 healthy fasting subjects will be conducted with a) placebo (water), b) a metabolic acetate generator (triacetin), and c) a half or d) one unit of isotope labelled ethanol, provided in a randomized order. Volunteers will be confined in a metabolic chamber overnight before each test drink (in 250mL water with lemon and juniper taste) and energy production and expenditure will be measured initially using seven ventilated hood measurements. After the test drinks and ventilated hood measurements an ad libitum lunch will be served before the participants will be admitted to the metabolic chamber, where metabolic measurements will be continued until the following day. Participants will go through a 2-week run-in period before each test drink and a 2-week wash out period afterwards, both with alcohol abstention. From two days before the test day in each period until one day after the test days, standardized foods will be provided. Anthropometrics, DXA, heart rate, blood pressure and all movements will be recorded before and/or during the test days. Before, during, and after the test day repeated biological samples (i.e., urine, blood, feces, hair) will be collected. The study will be divided into a pre-trial (8 subjects, 50-75y) and a main trial (16 subjects, 25-75y).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment order A-.B-C-D | Experimental | Dietary Supplement: EthanolA: 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 |
| Treatment order B-D-A-C | Experimental | Dietary Supplement: EthanolA: 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 |
| Treatment order C-A-D-B | Experimental | Dietary Supplement: EthanolA: 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 |
| Treatment order D-C-B-A | Experimental | Dietary Supplement: EthanolA: 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 |
Who may qualify
- Ages
- 25 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (30 listed)
- 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:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EthanolCrossover meal study | Dietary supplement | Treatment order A-.B-C-D, Treatment order B-D-A-C, Treatment order C-A-D-B, Treatment order D-C-B-A |
Primary outcome
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.
11 secondary outcomes
Resting energy expenditure
Time frame: 0-3 hours after intake
substrate oxidation rate
Time frame: 0-3 hours after intake
diet induced thermogenesis
Time frame: 0-3 hours after intake
Biomarkers of alcohol intake in hair
Time frame: 0-1 month after intake
Biomarkers of alcohol intake in urine
Time frame: 0-1 month after intake
Biomarkers of alcohol intake in red blood cells
Time frame: 0-1 month after intake
Biomarkers of alcohol intake in blood serum or plasma
Time frame: 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
Isotope labelled metabolites
Time frame: 0-48 hours after intake
Heart rate and blood pressure
Time frame: 0-24 hours after intake
Alcohol levels in breath
Time frame: 0-8 hours after intake
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2023.
- Individual participant dataSharing planned: No. Samples are to be anonymized before being shared with other researchers if the case.
Related trials for Healthy
Not yet recruitingPhase 1
Dynamic Magnetic Resonance Imaging of Human Subarachnoid Space Using Intrathecal Gadolinium Contrast
Healthy Volunteers
RecruitingObservational study
Survey to Determine Incarcerated Persons' Views on Surrogate Decision Making
Healthy Volunteers
Active, not recruitingPhase 1
A Study to Learn How Different Amounts of the Study Medicine Called PF-07985631 Are Tolerated and Act in the Body of Healthy Adults
Healthy
Not yet recruitingObservational study
Collection and Distribution of Blood Components From Healthy Donors for In Vitro Research Use
Blood Donors, Apheresis
Recruiting
Metabolic Impact of VLCPUFA-Rich Fish Oil: A Clinical Study on Omega-3 Index Enhancement in Healthy Individuals
Fatty Acids, Omega-3, Fish Oils
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catalina Cuparencu, Postdoc contact
Lars O Dragsted, PhD principal investigator
University of Copenhagen
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ethanol in people with Healthy, run by University of Copenhagen at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lars Ove Dragsted, PhD (+45 35 33 26 94, ldra@nexs.ku.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SCFA dynamics (time frame: 0-48 hours after intake). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2023.