Human Auto-ethanol Formation and Acetate Signaling

NCT05130619 | Unknown DMC

• 1 other identifier: M240
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• 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.

  0-48 hours after intake

Secondary Outcomes (11)

• Resting energy expenditure

  0-3 hours after intake

• substrate oxidation rate

  0-3 hours after intake

• diet induced thermogenesis

  0-3 hours after intake

• Biomarkers of alcohol intake in hair

  0-1 month after intake

• Biomarkers of alcohol intake in urine

  0-1 month after intake

Other Outcomes (6)

• Microbiome composition

  0-48 hours after intake

• Microbiome functionality

  0-48 hours after intake

• Faecal pH

  0-48 hours after intake

Study Arms (4)

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

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

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

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

Dietary Supplement: Ethanol

Interventions

Ethanol DIETARY_SUPPLEMENT

Crossover meal study

Treatment order A-.B-C-D; Treatment order B-D-A-C; Treatment order C-A-D-B; Treatment order D-C-B-A

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Copenhagen: lead

Study Sites (2)

Department of Nutrition, Exercise and Sports, University of Copenhagen

Copenhagen, Frederiksberg C, 1958, Denmark

RECRUITING

Lars Ove Dragsted

Frederiksberg, 1958, Denmark

RECRUITING

MeSH Terms

Interventions

Ethanol

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Study Officials

• Lars O Dragsted, PhD

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lars Ove Dragsted, PhD

CONTACT

+45 35 33 26 94; ldra@nexs.ku.dk

Catalina Cuparencu, Postdoc

CONTACT

cup@nexs.ku.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: November 23, 2021
• Study Start: November 10, 2021
• Primary Completion: April 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 30, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)