|- candidate number||13366|
|- NTR Number||NTR3629|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||25-sep-2012|
|- Secondary IDs||NL42072.018.12 CCMO|
|- Public Title||The effect of antibiotics and the gut flora on the immune system.|
|- Scientific Title||The role of the microbiota in the systemic immune response.|
|- hypothesis||Depletion of the gut microbiota by antibiotics leads to accelerated immunosuppression during sepsis, caused by decreased release of microorganism associated molecular patterns (MAMPs) and other microbiota derived products into the circulation and diminished priming of bone marrow neutrophils.|
|- Healt Condition(s) or Problem(s) studied||Sepsis, Gut flora depletion, Systemic immune respons|
|- Inclusion criteria||1. Healthy;|
2. Male between 18 and 35 years of age;
3. Capable of giving written informed consent and able to comply with the requirements
4. Chemistry panel without any clinically relevant abnormality;
5. Normal defecation pattern (defined as <3x/ day and >3x/week).
|- Exclusion criteria||1. Major illness in the past 3 months or significant chronic medical illness;|
2. History of any type of malignancy;
3. Past or current gastrointestinal disease which may influence the gut microbiota;
4. Known positive test for hepatitis C antibody, hepatitis B surface antigen or HIV;
5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities;
6. Use of tobacco products;
7. History, within 3 years, of drug abuse;
8. History of alcoholism and/or drinking more than 3 units of alcohol per day;
9. The subject has received an investigational product within three months of day 1;
10. Use of prescription or non-prescription drugs and herbal and dietary supplements within 6 months;
11. Recent (< 12 months) use of antibiotics (any kind, except for dermal antibiotics);
12. Allergy to antibiotics (any kind);
13. Difficulty swallowing pills;
14. Any other relevant issue.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||15-jan-2013|
|- planned closingdate||15-feb-2015|
|- Target number of participants||12|
|- Interventions||All volunteers will self-administer the following antibiotics for 7 consecutive days (concomitantly):|
1. Vancomycin 250mg 3dd2;
2. Ciprofloxacin 500mg 2dd1;
3. Metronidazol 500mg 3dd1.
|- Primary outcome||Side effects, laboratory measurements, functional assays and microbiota composition.
1. Side effects will be registered using a graded scale;
2. A HITchip (16S rRNA) analysis to determine microbiome composition;
3. Laboratory measurements: include inflammatory markers, neutrophil activation and -degranulation;
4. Functional assays: ex vivo stimulation of blood cells with nosocomial pathogens.
|- Secondary outcome||N/A|
|- Timepoints||T=0, day 8, week 7.|
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES|| J.M. Lankelma|
|- CONTACT for SCIENTIFIC QUERIES||Dr. W.J. Wiersinga|
|- Sponsor/Initiator ||Academic Medical Center (AMC)|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development|
|- Brief summary||Objective: |
To investigate the role of the gut microbiota in the systemic priming of immune effector cells.
Within-subject-controlled intervention study in human volunteers.
Twelve healthy male subjects, 18-35 years of age.
All subjects will be treated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days, in order to deplete the gut microbiota. Blood and faeces will be sampled before, 24 hours and 6 weeks after the 7-day period of antibiotics.
Main study endpoints:
Laboratory parameters for inflammatory responses, functional assays (ex vivo stimulation assay) and gut microbiota composition.
|- Main changes (audit trail)|
|- RECORD||25-sep-2012 - 2-sep-2013|