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

NCT07295314 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: 2023.0143
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gut Microbiome; Healthy Adult Male; Antifungal Therapy

Keywords

Fluconazole; Antifungal Drugs; Mycobiome; Bacteriome; Microbiota Diversity; Innate Immune Response; Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Gut microbiome and mycobiome composition at 6 months post-treatment

  6 months post-treatment

• Gut microbial functional profiles after fluconazole treatment

  Baseline, 14 days, 4 weeks, and 6 months

• Systemic innate immune responses after fluconazole treatment

  Baseline, 14 days, 4 weeks, and 6 months

Study Arms (2)

Fluconazole

EXPERIMENTAL

Participants will receive oral fluconazole 200mg once daily for 14 days.

Drug: Fluconazole 200mg tab

No Intervention

NO INTERVENTION

Participants assigned to the control arm will not receive any treatment.

Interventions

Fluconazole 200mg tab DRUG

Oral administration of one 200 mg fluconazole tablet once daily for 14 days.

Fluconazole

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Healthy males are eligible to participate.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Amsterdam UMC

Amsterdam, 1105 AZ, Netherlands

Location

MeSH Terms

Interventions

Fluconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomized to receive fluconazole or no intervention in a parallel-group design.

Study Record Dates

• First Submitted: December 8, 2025
• First Posted: December 19, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)