Effect of Saccharomyces Boulardii CNCM I-745 on Gut Microbiota in Patients Undergoing Antibiotic Therapy (in the Context of Erythema Migrans (Early Skin Form of Lyme Borreliosis))

NCT06451913 | Recruiting Phase 4

• 2 other identifiers: SUBLYME - Sb 2412023-508694-80-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to assess the effect of Saccharomyces boulardii CNCM I-745 on gut microbiota in patients undergoing antibiotic therapy (in the context of erythema migrans (early skin form of Lyme borreliosis)).

Conditions

Erythema Migrans of Lyme Disease

Keywords

Erythema Migrans; Lyme Disease; Gut microbiota; Saccharomyces boulardii CNCM I-745; Lyme borreliosis

Outcome Measures

Primary Outcomes (1)

• Assessment of the effect of Saccharomyces boulardii CNCM I-745, an antibiotic, and their combination on the gut microbiota of patients receiving antibiotic

  Primary endpoint : analysis of the intestinal microbiota in the patient's stools

  At Day 1, Day 7, Day 14 and Day 21

Secondary Outcomes (3)

• Assessment of the efficacy of Saccharomyces boulardii CNCM I-745 in prevention of antibiotic-associated diarrhoea (AAD) in patients undergoing antibiotic therapy

  At Day 1, Day 7, Day 14 and Day 21

• Assessment of the efficacy of Saccharomyces boulardii CNCM I-745 on the stools in patients undergoing antibiotic therapy : Recorded stools in the Bristol Stool Form Scale (BSFS)

  At Day 1, Day 7, Day 14 and Day 21

• Assess the effect of Saccharomyces boulardii CNCM I-745, an antibiotic, and their combination on the gastro-intestinal symptoms of patients receiving antibiotic therapy : Changes from baseline of the GSRS

  Weekly from Day 1 to Day 21

Other Outcomes (3)

• Assessment of the safety and tolerability of Saccharomyces boulardii CNCM I-745. Recording adverse events

  At each assessment time from baseline (Day 1 to Day 58)

• Assess the effect of Saccharomyces boulardii CNCM I-745, an antibiotic, and their combination on the specific gastro-intestinal symptoms of patients receiving antibiotic therapy : Gastrointestinal Symptom Rating scale (GSRS)

  Weekly from Day 1 to Day 21

• Assess the effect of Saccharomyces boulardii CNCM I-745, an antibiotic, and their combination on the gut resistome of patients receiving antibiotic : Changes on the fecal Antimicrobial Resistance Genes (ARGs)

  At Day 1, Day 7, Day 14 and Day 21

Study Arms (2)

Amoxicillin + Saccharomyces boulardii CNCM I-745

EXPERIMENTAL

The patients will received oral Amoxicillin (1000 mg capsules bid) for 14 days and oral Saccharomyces boulardii CNCM I-745 (®) 250 mg x 2 capsules twice a day for 21 days.

Drug: Amoxicillin + Saccharomyces boulardii CNCM I-745; Other: Stool samples; Other: BSFS : Bristol Stool Form Scale; Other: GSRS : Gastrointestinal Symptom Rating Scale

Amoxicillin + Placebo

PLACEBO COMPARATOR

The patients will received oral Amoxicillin (1000 mg capsules bid) for 14 days + oral Placebo capsules for 21 days.

Drug: Amoxicillin + Placebo; Other: Stool samples; Other: BSFS : Bristol Stool Form Scale; Other: GSRS : Gastrointestinal Symptom Rating Scale

Interventions

Amoxicillin + Saccharomyces boulardii CNCM I-745 DRUG

At inclusion visit (V1), the Investigator will dispense and ask the subject to take Amoxicillin 1000 mg bid for 14 days + Saccharomyces boulardii 250 mg x 2 twice a day for 21 days

Amoxicillin + Saccharomyces boulardii CNCM I-745

Amoxicillin + Placebo DRUG

At inclusion visit (V1),the Investigator will dispense and ask the subject to take Amoxicillin 1000 mg bid for 14 days + a matching placebo bid for 21 days

Amoxicillin + Placebo

Stool samples OTHER

The subject will be asked to collect thanks to four OMNIgene® •GUT OMR-200 kits : * an initial stool collection when returning home at D1 (in any case before any intake of amoxicillin and of the investigational medication and up to 1 day after D1). * a stool collection at home after the phone call 1, Day 7 (stool collection up to Day 7 + 1 day) * a stool collection at home after the phone call 2, Day 14 (stool collection up to Day 14 + 1 day) * at home the day of the Visit 2, Day 21 (stool collection up to Day 21 + 1 day)

Amoxicillin + Placebo; Amoxicillin + Saccharomyces boulardii CNCM I-745

BSFS : Bristol Stool Form Scale OTHER

All included subjects will have to complete a stool diary BSFS (Bristol Stool Form Scale) daily and at each bowel movement, from Day 1 until the end of study treatment (Day 21). The patient will fill the form with the date, the time, and the stool texture.

Amoxicillin + Placebo; Amoxicillin + Saccharomyces boulardii CNCM I-745

GSRS : Gastrointestinal Symptom Rating Scale OTHER

All included subjects will have to complete a GSRS (Gastrointestinal Symptom Response Score) questionnaire weekly from Day 1 until the end of the study treatment (Day 21).

Amoxicillin + Placebo; Amoxicillin + Saccharomyces boulardii CNCM I-745

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult Patients, ≥18 years old.
• Who are prescribed antibiotic therapy (as per medical routine practices, amoxicillin 1000 mg bid for 14 days) in the context of erythema migrans (early skin form of Lyme borreliosis).
• Able to comply with study requirements and to provide signed informed consent before any study procedure.
• Has no condition that may interfere with the study assessments.
• Able to fulfil in the diary stool log, according to the physician's opinion.
• Regular defecation (frequency and stool consistency, with at least about three bowel movements a week).
• For women of childbearing potential:
• A negative urine pregnancy test immediately prior to starting the study treatment,
• Agreement to comply with approved methods of contraception during the whole study: unless they meet the criteria of post-menopausal, i.e. 12 months of spontaneous amenorrhea, women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner, should use one or more acceptable methods of contraception that should be maintained throughout the study.

You may not qualify if:

• History of hypersensitivity to the study treatments (active substance or excipients), brewer's or baker's yeast,
• Contraindication and special warning to the study drugs according to the SmPCs,
• History of chronic constipation with passage of fewer than 3 spontaneous bowel movements per week on average,
• History of chronic or recurrent diarrhoea with spontaneous unformed bowel movements equivalent to or more often than 3 times daily,
• Prior gastrointestinal surgery (apart from appendectomy or cholecystectomy performed at least more than one year ago),
• History of Clostridium difficile infection,
• Active gastrointestinal inflammatory disease,
• Known chronic or recurrent systemic disorder that may interfere with the study drug evaluation,
• Immunocompromised (organtransplants, leukaemia, malignant tumours, radiotherapy, chemotherapy,prolonged high dose cortisone treatment, immunosuppressant treament) or critically ill patients (such as autoimmune disease, HIV,…), patients with a central venous catheter,
• Severe hepatic or renal impairment,
• Systemic antibacterial therapy during the 2 months prior to study enrollment,
• New prescription medications during the 2 weeks prior to study enrollment,
• Use of any drug or product that alters gut microbiota or function, such as probiotics, laxatives, antiemetics, cisapride, antisecretory or adsorbent treatments (racecadotril, smectite, activated charcoal), opiates such as loperamide, atropine and other cholinergic agents, 4 weeks prior to study enrollment and during the study,
• Intake of antifungals within 14 days prior to study enrollment,
• Substantial changes in eating habits within 30 days prior to receiving the first dose of IMP product, and during the study as assessed by the Investigator,

Sponsors & Collaborators

• Biocodex: lead

Study Sites (1)

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

RECRUITING

MeSH Terms

Conditions

Erythema Chronicum Migrans; Glossitis, Benign Migratory; Lyme Disease

Interventions

Amoxicillin

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Borrelia Infections; Spirochaetales Infections; Skin Diseases, Bacterial; Skin Diseases, Infectious; Tick-Borne Diseases; Vector Borne Diseases; Erythema; Skin Diseases; Skin and Connective Tissue Diseases; Glossitis; Tongue Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Oana BERNARD, MD

  Chief Scientific Officer

  STUDY DIRECTOR

Central Study Contacts

Gaëlle MARIAULE

CONTACT

03.44.86.82.28; g.mariaule@biocodex.fr

Carine FRANCOIS

CONTACT

03.44.86.82.28; c.francois@biocodex.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The 2 types of investigational products will be checked for blind maintenance before release (capsules will be identical in size, shape, color and appearance). The principal investigator does not have access to the randomization (treatment) code, except in exceptional circumstances for valid medical or safety reason, such as occurrence of a serious adverse event for which the knowledge of the study medication would be considered essential for treating the patient.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, parallel-group, comparative study

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: June 11, 2024
• Study Start: July 16, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)