To study the effects of the gut flora on serum LDL-cholesterol concentrations in slightly hypercholesterolemic subjects. The minor objective is to study the effects of gut flora on other parameters related to lipid and lipoprotein, and to parameters…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the change in fasting serum LDL-cholesterol
concentrations.
Secondary outcome
Secundary study parameters are changes in concentrations of HDL cholesterol,
triacylglycerol and glucose. Changes in ex vivo and in vitro lipolysis in
abdominal subcutaneous adipose and in skeletal tissue will be measured in a
subgroup.
Background summary
There is substantial evidence from in particular animal studies that the gut
microbiota is related to lipid and lipoprotein metabolism. It is not known
however to what extent modulation of the gut microbiota in humans changes lipid
and lipoprotein metabolism.
Study objective
To study the effects of the gut flora on serum LDL-cholesterol concentrations
in slightly hypercholesterolemic subjects. The minor objective is to study the
effects of gut flora on other parameters related to lipid and lipoprotein, and
to parameters related to glucose metabolism.
Study design
Using a randomized, double-blind, placebo-controlled parallel design, subjects
will receive for 7 days a broad spectrum antibiotic (Amoxicillinum Gb; daily
3x500 mg) or placebo.
Intervention
During the experimental period, subjects will receive daily 6x250 Amoxicillinum
Gb or placebo for 7 days. Placebo capsules will be filled with gelatine,
cellulosum microcristallinum PH102. Blood samples will be taken at regular
intervals.
Men and women aged between 18-70 years and with a BMI >18.5 kg/m2 will be asked
if they are willing to collect an abdominal adipose tissue biopsy and skeletal
muscle biopsy.
Study burden and risks
Before the start of the study subjects will be screened to determine
eligibility during two 15-minute visits. During these visits, body weight,
height and blood pressure will be measured and a blood sample (4.5 mL) will be
drawn by means of venapunction. During the study, subjects will receive a
broad-spectrum antibiotic or placebo for 7 days. At days 1, 4, 8, 12 and 16, a
fasting blood sample will be drawn (20 mL at each occasion) and (in a subgroup)
on days 1 and 8 biopsies of subcutaneous adipose and skeletal tissue. Subjects
will be asked to fill out a 3-day food record two times and to keep a
study-diary throughout study. On rare occasions, blood sampling / taking
biopsies might cause bruises or hematoma. Amoxicillin can cause
gastrointestinal complaints like diarrhea or stomach ache. Additionally
allergic skin reactions, interstitial nephritis and blood disturbances like
hemolytic anemia and thrombocytopenia may occur. These effects, however, have
been reported scarcely. Total time investment for the subjects will be
approximately 4 hours and 6 hours for those who are willing to participate in
the sub-study to collect biopsies.
Universiteitssingel 50
Maastricht 6223 ER
NL
Universiteitssingel 50
Maastricht 6223 ER
NL
Listed location countries
Age
Inclusion criteria
- aged between 18-70 years
- mean serum total cholesterol concentrations between 5.0 - 8.0 mmol/L
Exclusion criteria
- mean serum triacylglycerol > 3.0 mmol/L
- use of oral anticonceptives (OAC)
- pregnant or breastfeeding women
- subjects with kidney insufficiencies (defined as creatinine clearance <30 mL/min).
- unstable body weight (weight gain or loss >2 kg in the past 3 months)
- known allergy to antibiotics
- indication for treatment with cholesterol-lowering drugs according to the Dutch Cholesterol Consensus
- use of medication or a medically prescribed diet known to affect lipid or glucose metabolism
- active cardiovascular disease like congestive heart failure or recent (<6 months) event (acute myocardial infarction, cerebro vascular accident)
- severe medical conditions that might interfere with the study such as epilepsy, asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases and rheumatoid arthritis
- abuse of drugs
- more than 21 alcohol consumptions per week for men and 14 consumptions for women
- not or difficult to venipuncture as evidenced during the screening visits
- use of an investigational product within the previous 30 days
- not willing to stop the consumption of products rich in plant stanol or sterol esters 3 weeks before the start of the study
- not willing to give up being a blood donor (or having donated blood) from 8 weeks before the start of the study and during the study
- use of gastric acid inhibitors, laxantia, prebiotica, probiotica and antibiotica for at least one month before the start of the study and during the 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 |
|---|---|
| ClinicalTrials.gov | NCT- |
| CCMO | NL39874.068.12 |