FGF21 and Its Role in Alcohol Dependence

Study Overview
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Brief Summary
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Plasma fibroblast growthfactor-21 (FGF21) responses to acute alcohol exposure will be evaluated in three groups: A: 15 individuals diagnosed with alcohol dependence (ICD10 code F10.2) and no alcoholic liver diseases, B: 15 healthy individuals with one or two parents with alcohol dependence, and C: 15 healthy matched controls without history of or disposition to alcohol dependence. The experimental day consists of a load of 0.5 g ethanol per kg body weight ingested from time 0-10 minutes followed by a 7 h period in which blood will be sampled with frequent intervals, rating of preference for ethanol, salt, sour, bitterly and sweets, sensations of hunger, appetite, satiety, headache, and nausea will be evaluated using visuel analogue scale and resting energy expenditure will be evaluated using indirect calorimetry.

Official Title
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Physiological Effects of FGF21 in Humans and Its Pathophysiological Role in Alcohol Dependence

Conditions
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Alcohol Abuse or Dependence

Intervention / Treatment
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* Other: Ethanol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Caucasian males between 25 and 65 years of age BMI between 19 and 27 kg/m2 Normal haemoglobin Normal fasting plasma glucose concentration (< 6 mmol/l) and normal glycated haemoglobin A1c (HbA1c) (< 42 mmol/mol) Participants with a father diagnosed with alcohol dependence (group B): Father diagnosed with alcohol dependence Weekly alcohol intake of less than 14 units of alcohol (of 12 g) Normal Alcohol Use Disorders Identification Test (AUDIT) score Healthy participants (group C): Weekly alcohol intake of less than 14 units of alcohol (of 12 g) Normal AUDIT score Exclusion Criteria: Liver disease evaluated by plasma alanine aminotransferase (ALAT) > 3 × normal level, an international normalised ratio (INR) below normal values, or biopsy-verified alcoholic liver disease Diabetes mellitus Anaemia Nephropathy Other diseases the investigator finds disruptive for participation in the study. Participants with a father diagnosed with alcohol dependence (group B): - Former alcohol dependence or abuse Healthy participants (group C): First-degree relatives with diabetes, liver disease and/or alcohol dependence Former alcohol dependence

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Three matched groups. Group A: participants diagnosed with alcohol dependence, group B: participants with a father diagnosed with alcohol dependence, and C: a healthy control group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alcohol<br>The participant receive 0.5 g ethanol per kg body weight over 10 minutes. Subsequently blood samples are taken frequently the next ten hours. | Other: Ethanol<br>* Ethanol administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibroblast growthfactor-21 | Plasma FGF21 concentrations, a member of the endocrine FGF-family | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ethanol | Plasma ethanol concentration | One year | 
| Glucose | Plasma glucose concentrations | One year | 
| Insulin and C-peptide | Serum insulin and C-peptide concentrations | One year | 
| Glucagon | Plasma glucagon concentration | One year | 
| Tumor Necrosis Factor-alpha (TNF) | Plasma TNF-alpha concentrations | One year | 
| Lipopolysaccharide Binding Protein (LBP) | Plasma LBP concentrations | One year | 
| Interferon-gamma (INF) | Plasma INF-gamma concentrations | One year | 
| Interleukine-10 (IL-10) | Plasma IL-10 concentrations | One year | 
| Interleukine-8 (IL-8) | Plasma IL-8 concentrations | One year | 
| Interleukine-6 (IL-6) | Plasma IL-6 concentrations | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcohol, FGF21, Alcohol dependence