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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Phenomena and Processes [G] - Microbiological Phenomena [G06]

Trial duration

5 Jan 2026 → ongoing

Decision date (initial)

2023-07-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

to investigate the effect of an antifungal drug (fluconazole) on the intestinal microbiota.

Secondary objectives 1

1. 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.

Conditions and MedDRA coding

Not applicable - Healthy Volunteer study

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male
2. 18-35 years of age at the time of signing the informed consent
3. 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
4. Capable of giving written informed consent and able to comply with the requirements and restrictions listed in the informed consent form
5. Normal defecation pattern (defined as ≤3x/ day and ≥3x/week)

Exclusion criteria 14

1. 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
2. Subject has a past or current gastrointestinal disease which may influence the gut microbiota, including inflammatory bowel disease and medication-treated irritable bowel syndrome
3. Subject with any history of immunodeficiency
4. Subject with a history of any type of malignancy
5. Drinking more than an average of 3 units of alcohol per day
6. Known allergy to antifungals (any kind)
7. Recent (< 3 months) use of antibiotics (any kind, except for dermal antibiotics)
8. Recent (< 3 months) use of antifungals (any kind, except for dermal antifungals)
9. Planned prolonged (> 4 weeks) travel to tropical countries during the study period
10. The subject has received an investigational product within three months of day 0 of the current study
11. 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
12. Subject has difficulty in donating blood or accessibility of a vein in left or right arm
13. Subject has donated more than 500 mL of blood in last 3 months
14. Any other issue that, in the opinion of the investigator, could be harmful to the subject or compromise interpretation of the data

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 3

1. 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
2. Differences in gut microbial functional profiles (in the form of metabolic pathways and in vitro faecal microbial fermentation) between arms at the different timepoints
3. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

P. O. Box 7057

City

Amsterdam

Postcode

1007 MB

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

W.J. Wiersinga

Public contact point

Organisation

Amsterdam UMC

Contact name

W.J. Wiersinga

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications