Effect of Antifungals on the Intestinal Microbiome - a Randomized, Controlled, Proof-of-concept Trial (FAME)

The goal of this clinical trial is to learn how the antifungal drug fluconazole affects the gut microbiome and immune system in healthy volunteers.

The main questions it aims to answer are:

• Does fluconazole change the gut bacteriome and mycobiome composition after 14 days of treatment?
• How long do these changes last (4 weeks and 6 months after treatment)?
• Does fluconazole affect the body's immune responses, such as blood cell activity and antifungal antibodies?

Researchers will compare two groups: participants who take fluconazole for 14 days and participants who receive no intervention.

Participants will:

• Either take one fluconazole tablet (200 mg) daily for 14 days, or receive no treatment
• Provide stool samples and blood samples at several timepoints
• Return for follow-up visits up to 6 months after treatment

This study is conducted at Amsterdam UMC, location AMC, with a planned enrollment of 50 healthy male volunteers aged 18-35 years.

Study Overview

• Status: Not yet recruiting
• Conditions: Gut Microbiome; Healthy Adult Male; Antifungal Therapy
• Intervention / Treatment: Drug: Fluconazole 200mg tab

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC
    • Contact: Rebekka Bout; Phone Number: +31205669111; Email: r.rebel@amsterdamumc.nl
    • Contact: Duveke de Gaay Fortman, MD; Phone Number: +3120566 9111; Email: p.d.e.degaayfortman@amsterdamumc.nl
    • Principal Investigator: WJ Wiersinga, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male, 18-35 years of age at the time of signing informed consent
• Healthy, as determined by medical history and physical examination; minor clinical abnormalities allowed if not introducing additional risk or interfering with study procedures
• Capable of giving written informed consent and able to comply with study requirements
• Normal defecation pattern (≤3 times/day and ≥3 times/week)

Exclusion Criteria:

• Major illness in the past 3 months, or significant chronic medical illness deemed unfavorable for enrollment
• Past or current gastrointestinal disease that may influence the gut microbiota (including inflammatory bowel disease or medication-treated irritable bowel syndrome)
• History of immunodeficiency
• History of malignancy
• Alcohol intake >3 units/day on average
• Known allergy to antifungal drugs
• Use of antibiotics (except topical) within the past 3 months
• Use of antifungals (except topical) within the past 3 months
• Planned prolonged travel (>4 weeks) to tropical countries during the study period
• Receipt of an investigational product within 3 months prior to study day 0
• Use of prescription or non-prescription drugs, herbal or dietary supplements within 3 months (unless deemed safe by investigator)
• Difficulty with blood donation or poor venous access in either arm
• Donation of >500 mL of blood in the past 3 months
• Any other condition or circumstance that, in the investigator's opinion, could be harmful to the subject or compromise data interpretation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluconazole; Participants will receive oral fluconazole 200mg once daily for 14 days.	Drug: Fluconazole 200mg tab; Oral administration of one 200 mg fluconazole tablet once daily for 14 days.
No Intervention: No Intervention; Participants assigned to the control arm will not receive any treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of fluconazole on the intestinal microbiome	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).	14 days (end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome and mycobiome composition at 6 months post-treatment	Differences in gut bacteriome and mycobiome composition, including α- and β diversity, between fluconazole and no-intervention arms and compared to baseline, 6 months after completion of fluconazole treatment.	6 months post-treatment
Gut microbial functional profiles after fluconazole treatment	Differences in gut microbial functional profiles, including metabolic pathways and in vitro fecal microbial fermentation, between fluconazole and no-intervention arms	Baseline, 14 days, 4 weeks, and 6 months
Systemic innate immune responses after fluconazole treatment	Differences in host systemic innate immune response profiles between fluconazole and no-intervention arms at baseline, 14 days, 4 weeks, and 6 months. Responses will be assessed using ex vivo stimulation assays of peripheral blood mononuclear cells and neutrophils, and measurement of antifungal antibodies.	Baseline, 14 days, 4 weeks, and 6 months

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 8, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Fluconazole; Healthy Volunteers; Mycobiome; Innate Immune Response; Microbiota Diversity; Antifungal Drugs; Bacteriome
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Triazoles; Fluconazole
• Other Study ID Numbers: 2023.0143

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No