Primary objective: To explore whether prolonged moderate alcohol consumption affects in vivo cytokine response after a low dose of LPS in young, normal-weight men.Secondary objectives: To explore whether prolonged moderate alcohol consumption-…
ID
Source
Brief title
Condition
- Endocrine and glandular disorders NEC
- Gastrointestinal signs and symptoms
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Cytokine response in a human model of low-grade systemic inflammation:
- TNF-α and IL-6 response after intravenous (i.v.) LPS administration
- Alcohol-induced increase in HDL
Secondary outcome
De novo adiponectin protein synthesis rate:
Percentage of 14C in adiponectin after i.v. 14C labeled leucine administration
Gut microbiota in faeces:
Changes in composition of feacal flora and in short chain fatty acids of faeces
Background summary
High-density lipoprotein (HDL), which is consistently increased after moderate
alcohol consumption, is an abundant plasma lipoprotein that is generally
thought to be anti-inflammatory in both health and infectious disease. HDL
binds and neutralizes the bioactivity of potent bacterial remnants such as
lipopolysaccharides (LPS) which stimulate the host innate immune responses.
Study objective
Primary objective: To explore whether prolonged moderate alcohol consumption
affects in vivo cytokine response after a low dose of LPS in young,
normal-weight men.
Secondary objectives: To explore whether prolonged moderate alcohol consumption
- increases the de novo adiponectin protein synthesis and
- changes the composition of gut microbiota in faeces
in young, normal-weight men.
Study design
Randomized, placebo-controlled, open-label crossover trial
Intervention
Daily consumption of 100 mL of vodka (30 gram alcohol/day) together with 200 mL
orange juice (test) or 200 mL of orange juice (control) for four weeks.
Study burden and risks
Subjects need to visit the study site nine times during the study period of 57
days (see figure § 11.4). In these visits fasted blood (4x), urine (8x), faeces
(2x) and adipose tissue samples from the buttocks (2x) will be collected and
body weight measurements (9x) will be performed. The total amount collected
during the whole study will be around 200 mL blood, 16 mL urine, and 600 mg
subcutaneous adipose tissue.
The study will be performed in young people since this population is more
susceptible for alcohol-induced improvements in HDL-cholesterol after prolonged
moderate alcohol consumption (1). Based on two previous studies (2;3) with the
same LPS strain (P8600 B11) and the same intended bolus dose of 0.06 ng/kg body
weight among the same population (young males), did not result in any serious
adverse effects nor in a rise of body temperature. Besides a slight feeling of
coldness, no other side effects are expected (see P8600 B11). Therefore, the
LPS strain and dose can be regarded as safe.
Although carbon-14 (P8600 B10) is radioactive, the amount used (total 47 ng)
and the exposure to beta radiation (3.6 kBq, total 100 nCi) is low. The
radioactive dose equivalent is around 2 µSv, which would result in an increase
of the yearly radioactive dose equivalent of less than 1% of natural background.
Based on our previous experiences with alcohol studies with higher daily
dosages of alcohol (Beulens) in a similar population for the same period of
time and based on our previous experiences with intravenous tracer studies, we
do not foresee any risk associated with participation in this study.
Dagelijkse Groenmarkt 3-5
2513 AL Den Haag
Nederland
Dagelijkse Groenmarkt 3-5
2513 AL Den Haag
Nederland
Listed location countries
Age
Inclusion criteria
1. Healthy as assessed by the health and lifestyle questionnaire (P8600 F02), physical examination and results of the pre-study laboratory tests
2. Caucasian males aged 21-40 years at Day 01 of the study.
3. Body Mass Index (BMI) of 18 - 27 kg/m2.
4. Alcohol consumption >= 5 and <= 28 standard units/week.
5. Normal Dutch eating habits as assessed by P8600 F02.
6. Voluntary participation.
7. Having given written informed consent.
8. Willing to comply with the study procedures, including refrain from drinking alcoholic drinks other then the alcoholic beverage provided by TNO during the entire study and refrain from fermented dairy and probiotics-containing products.
9. Willing to accept use of all nameless data, including publication, and the confidential use and storage of all data for at least 15 years.
10. Willing to accept the disclosure of the financial benefit of participation in the study to the authorities concerned.
Exclusion criteria
Subjects with one or more of the following characteristics will be excluded from participation:
1. Participation in any clinical trial including blood sampling and/or administration of substances up to 90 days before Day 01 of this study.
2. Participation in any non-invasive clinical trial up to 30 days before Day 01 of this study, including no blood sampling and/or oral, intravenous, inhalatory administration of substances.
3. Having a history of medical or surgical events or disease that may significantly affect the study outcome, particularly metabolic or endocrine disease and gastrointestinal disorders.
4. Use of medication that may affect the outcome of the study parameters.
5. Having a family history of alcoholism.
6. Smoking.
7. Not having appropriate veins for blood sampling/cannula insertion according to TNO.
8. Reported unexplained weight loss or gain in the month prior to the pre-study screening.
9. Reported slimming or medically prescribed diet.
10. Reported vegan, vegetarian or macrobiotic.
11. Recent blood donation (<1 month prior to the start of the study).
12. Not willing to give up blood donation during the study.
13. Personnel of TNO Quality of Life, their partner and their first and second degree relatives.
14. Not having a general practitioner.
15. Not willing to accept information transfer which concerns participation in the study, or information regarding health, like laboratory results, findings at anamnesis or physical examination and eventual adverse events to and from his general practitioner.
16. Not willing your general practitioner to be notified upon participation in this study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL28554.028.09 |