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Effect of antifungals on the intestinal microbiome – a randomized, controlled, proof-of-concept trial

Phase 1
Conditions
ot applicable - Healthy Volunteer study
Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]
Therapeutic area: Phenomena and Processes [G] - Microbiological Phenomena [G06]
Registration Number
CTIS2023-503710-69-00
Lead Sponsor
Amsterdam UMC
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Male
Target Recruitment
50
Inclusion Criteria

Male, 18-35 years of age at the time of signing the informed consent, Healthy, as determined by a responsible physician, based on a medical evaluation including medical history and physical examination. A subject with a clinical abnormality may be included if the investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures, Capable of giving written informed consent and able to comply with the requirements and restrictions listed in the informed consent form, Normal defecation pattern (defined as =3x/ day and =3x/week)

Exclusion Criteria

Subject has had a major illness in the past 3 months or any significant chronic medical illness that the investigator would deem unfavourable for enrolment, The subject has received an investigational product within three months of day 0 of the current study, Use of prescription or non-prescription drugs and herbal and dietary supplements within 3 months unless in the opinion of the investigator the medication will not interfere with the study procedures or compromise subject safety, Subject has difficulty in donating blood or accessibility of a vein in left or right arm, Subject has donated more than 500 mL of blood in last 3 months, Any other issue that, in the opinion of the investigator, could be harmful to the subject or compromise interpretation of the data, Subject has a past or current gastrointestinal disease which may influence the gut microbiota, including inflammatory bowel disease and medication-treated irritable bowel syndrome, Subject with any history of immunodeficiency, Subject with a history of any type of malignancy, Drinking more than an average of 3 units of alcohol per day, Known allergy to antifungals (any kind), Recent (< 3 months) use of antibiotics (any kind, except for dermal antibiotics), Recent (< 3 months) use of antifungals (any kind, except for dermal antifungals), Planned prolonged (> 4 weeks) travel to tropical countries during the study period

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: to investigate the effect of an antifungal drug (fluconazole) on the intestinal microbiota.;Secondary Objective: To investigate the effect duration of fluconazole on the intestinal microbiota and to explore the role of mycobiome disruptions by antifungal treatment on systemic host immune responses.;Primary end point(s): Difference in gut bacteriome and mycobiome composition, ?- and ß-diversity between adults treated with an antifungal (fluconazole) and no intervention directly after completion of antifungal treatment (t=14 days).
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s):Differences in gut bacteriome and mycobiome composition, ?- and ß-diversity between arms and compared to baseline, at 4 weeks after completion of fluconazole treatment, and at 6 months;Secondary end point(s):Differences in gut microbial functional profiles (in the form of metabolic pathways and in vitro faecal microbial fermentation) between arms at the different timepoints;Secondary end point(s):Differences in host systemic innate immune response profiles between arms at the different timepoints. Characterized by, amongst others, ex vivo stimulation assays of peripheral blood mononuclear cells and neutrophils, and measurement of antifungal antibodies
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