A single blind, placebo controlled, single center, randomized controlled pilot study to assess if low dose ciprofloxacin can induce antimicrobial resistance in Escherichia coli (HealthyFood Trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institute Of Tropical Medicine

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Microbiological Phenomena [G06]

Trial duration

23 Feb 2024 → 23 May 2024

Decision date (initial)

2023-11-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To quantify the individual shifts in the ciprofloxacin MIC distribution of E. coli in the human gastrointestinal tract and to compare the shifts between intervention and placebo

Secondary objectives 5

1. To describe per individual the MIC distributions, both at baseline and after administration of the intervention/placebo.
2. To describe per participant the percentage of inhibited E. Coli at the prespecified concentrations of ciprofloxacin (No ciprofloxacin, 0.002 mg/L, 0.004 mg/L, 0.008 mg/L, 0.016 mg/L, 0.03 mg/L, 0.06 mg/L, 0.125 mg/L, 0.250 mg/L), both at baseline and after intervention/placebo.
3. Describe if low dose ciprofloxacin ingestion in humans can induce reduced susceptibility to ciprofloxacin in E. coli – reduced susceptibility defined as a ciprofloxacin MIC ≥ 0.125 mg/L
4. All above mentioned objectives and endpoints will be repeated for “non-E.coli coliforms" (pink colonies)
5. Describe the concentration of ciprofloxacin in feces at baseline and day 30

Conditions and MedDRA coding

antimicrobial resistance in Escherichia coli

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Able and willing to provide written informed consent
2. At least 18 years old
3. Not taking any immunosuppressive agents and not clinically immunocompromised at the time of randomization
4. For females of childbearing potential only, willingness to practice continuous effective contraception during the study and a negative pregnancy test at the screening visit. Note: In accordance with ICH M3, the following will be classified as ‘effective contraception’: implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, or vasectomized partner.

Exclusion criteria 5

1. Use of any antibiotics in the previous 2 months of Visit 1
2. Known contra-indications or allergy to ciprofloxacin
3. Presence of any other condition, that will (likely) require the administration of another antibiotic at the time of randomization, as assessed by the treating physician
4. Pregnant or breastfeeding
5. Negative culture for E. coli at Visit 2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. If from the descriptive plots (see secondary objective 1) it becomes evident that there is an individual location shift (but the shape of the distribution remains the same), the individual difference in median ciprofloxacin MIC will be calculated (after intervention – baseline). Otherwise, the maximum absolute distance between the two individual empirical cumulative empirical distributions (ecdf’s) will be calculated (i.e. Kolmogorov-Smirnov test statistic).

Secondary endpoints 5

1. Individual MIC distributions
2. Percentage of inhibited E. coli at the prespecified concentrations of ciprofloxacin per participant and per time point (baseline and after administration of the intervention/placebo).
3. Percentage of inhibited E. coli ciprofloxacin MIC ≥ 0.125 mg/L per participant and per time point (baseline and after administration of the intervention/placebo). This coincides with the sum of % inhibited at ciprofloxacin MIC = 0.125 mg/L and ciprofloxacin MIC = 0.250 mg/L.
4. All above mentioned endpoints will be repeated for “non-E.coli coliforms"
5. Concentration of ciprofloxacin in feces at day 0 and 30

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institute Of Tropical Medicine

Sponsor organisation

Institute Of Tropical Medicine

Address

Nationalestraat 155

City

Antwerp

Postcode

2000

Country

Belgium

Scientific contact point

Organisation

Institute Of Tropical Medicine

Contact name

Chris Kenyon

Public contact point

Organisation

Institute Of Tropical Medicine

Contact name

Chris Kenyon

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 4 files

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

Application history

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