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Stool Biobanking and Impact of Antimicrobials on the Gut Microbiota in Patients With Bone and Joint Infection (GUMIBONE)

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ClinicalTrials.gov Identifier: NCT03633188
Recruitment Status : Recruiting
First Posted : August 16, 2018
Last Update Posted : January 17, 2019
Sponsor:
Collaborator:
University of Lyon
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:

Bone and joint infections (BJI) is a public health issue in industrialized countries.

Implant-associated BJI, are complex hospital-acquired infections and eradication of the pathogen is challenging in such patients.

A prolonged antimicrobial therapy is usually required from 6 weeks to 3 months, but some patients are eligible to several years of treatment and most of patients report gastrointestinal troubles, such as nausea and mild to severe diarrhea (but very few developed C. difficile diarrhea).

Moreover, the host gut microbiota is probably largely affected in abundance, richness and diversity. Indeed, it is known, that few days of antibiotics are sufficient to induce significant alterations of the gut microbiota, also called dysbiosis.

Severe dysbiosis, which is potentially irreversible and associated with a definitive shift in the gut microbiota metabolism and host homeostasis, may lead to and/or promote a large panel of severe diseases such as Clostridium difficile infection, diabetes mellitus, obesity, inflammatory bowel disease (IBD), cirrhosis, neurological disorders and cancer. It may also be associated with BJI recurrence and then impact global health costs.

The main objective of this study is to constitute biobanking of stools and perform DNA sequencing of the gut microbiota in patients with acute or sub-acute implant-related Bone and Joint Infection (BJI), caused by Staphylococcus aureus.


Condition or disease Intervention/treatment Phase
Infection, Bacterial Biological: Patients treated by antibiotherapy Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Stool Biobanking and Impact of Antimicrobials on the Gut Microbiota in Patients With Bone and Joint Infection
Actual Study Start Date : July 19, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Patients treated by antibiotherapy
35 Patients treated by antibiotherapy for acute and subacute post-operative implant-associated BJI infections and among them 10 patients with Staphylococcus. aureus treated with antibiotics as part of their standard treatment procedure for metagenomic procedure.
Biological: Patients treated by antibiotherapy

Biological samples (stool, blood, swabs) will be collected :

  • Blood sampling (12 ml) at baseline (week 0) at the end of treatment (W6/W24),and 15 days after antibiotherapy stop (optional) (W8/W26),
  • Feces collection at baseline (week 0) during antibiotic treatment (W2), at the end of treatment (W6/W24),15 days after antibiotherapy stop (W8/W26), and W26 after baseline
  • Swab samples (nasal and rectal) at baseline at week 0 and at the end of treatment (W6/W24),




Primary Outcome Measures :
  1. change in the gut microbiota after treatment [ Time Frame: from baseline to week 26 ]

    stools will be collected to perform DNA sequencing of the gut microbiota in patients with acute or sub-acute implant-related Bone and Joint Infection (BJI), caused by Staphylococcus aureus.

    Stools will be collected at baseline, during antibiotic treatment (Week 2), at the end of treatment (Week 6 or Week 24),15 days after antibiotherapy stop (Week 8 or Week 26), and W26 after baseline.



Secondary Outcome Measures :
  1. Assessment of the evolution of intensity of Diarrheic Symptoms [ Time Frame: from baseline to week 8 or week 26 ]
    intensity of diarrheic symptoms will be collected at baseline, at the end of treatment (Week 6 or Week 24) and 15 days after antibiotic stop (Week 8 or Week 26)

  2. Assessment of the evolution of frequency of Diarrheic Symptoms [ Time Frame: from baseline to week 8 or week 26 ]
    frequency of diarrheic symptoms will be collected at baseline, at the end of treatment (Week 6 or Week 24) and 15 days after antibiotic stop (Week 8 or Week 26)

  3. Quantity of rectal acquisition of Multi Drug Resistance (MDR) bacteria under antibiotics measured by classic culture and quantification culture methods [ Time Frame: at week 6 or week 24 ]

    classic culture and quantification culture methods determined by microbiology analysis of the feces.

    Feces will be collected at baseline and at the end of treatment


  4. gut dysbiosis measured by Next Generation Sequencing (NGS) [ Time Frame: from baseline to week 26 ]

    Stools will be collected at baseline, during antibiotic treatment (Week 2), at the end of treatment (Week 6 or Week 24),15 days after antibiotherapy stop (Week 8 or Week 26), and W26 after baseline.

    Microbiota sequencing will be done after DNA extraction. Composition of the microbiota will be screened in feces samples using the shotgun sequencing method to establish a total picture of the gut composition and diversity as well as evolution of the microbiome.


  5. severe post-antibiotic dysbiosis (SPAD) measured by Next Generation Sequencing (NGS) [ Time Frame: from baseline to week 26 ]

    Severe Post-Antibiotic Dysbiosis lead to irreversible change in gut microbiota status and systemic consequences for the host.

    Stools will be collected at baseline, during antibiotic treatment (Week 2), at the end of treatment (Week 6 or Week 24),15 days after antibiotherapy stop (Week 8 or Week 26), and W26 after baseline.


  6. Identification of markers of the gut dysbiosis (inflammatory proteins) measured by Elisa techniques [ Time Frame: from baseline to week 26 ]

    ELISA techniques will be used to determine the concentration of 3 specific inflammatory stool epithelium proteins: zonulin, calprotectin and neopterin.

    Stools will be collected at baseline, during antibiotic treatment (Week 2), at the end of treatment (Week 6 or Week 24),15 days after antibiotherapy stop (Week 8 or Week 26), and W26 after baseline.


  7. Analysis of impact of Bone and Joint Infection on health-related quality of life in patients by EQ5D5L questionnaires [ Time Frame: from baseline to week 26 ]

    EQ-5D questionnaire has 5 dimensions: "Mobility", "Human Autonomy," "Current Activities", "Pain / Discomfort", "Anxiety / Depression". All dimensions are described by 5 (EQ-5D-5L) problem levels corresponding to patient response choices.

    Questionnaire will be completed at baseline, during antibiotic treatment (Week 2), at the end of treatment (Week 6 or Week 24),15 days after antibiotherapy stop (Week 8 or Week 26), and W26 after baseline.


  8. Analysis of impact of Bone and Joint Infection on health-related quality of life in patients by EQ5D3L questionnaire [ Time Frame: from baseline to week 26 ]

    EQ-5D questionnaire has 5 dimensions: "Mobility", "Human Autonomy," "Current Activities", "Pain / Discomfort", "Anxiety / Depression". All dimensions are described by 3 (EQ-5D-3L) problem levels corresponding to patient response choices. In France, only the EQ-5D-3L has been validated, not yet the EQ-5D-5L which has only been translated.

    Questionnaire will be completed at baseline, during antibiotic treatment (Week 2), at the end of treatment (Week 6 or Week 24),15 days after antibiotherapy stop (Week 8 or Week 26), and W26 after baseline.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The subject is willing, able to understand and comply to the protocol requirement
  2. More than 18-years-old
  3. Subject with suspicion of implant-related BJI within 3 months after surgery and treated by antibiotherapy for a maximal duration of six months
  4. Subject signed Inform Consent Form
  5. Contraception for women of childbearing age

Exclusion Criteria:

  1. Pregnancy
  2. Severe disease with a life expectancy < 3months
  3. Any antibiotherapy treated all diseases in the 14 days before inclusion
  4. Guardianship, curatorship patients
  5. Patient non-affiliated to health care system
  6. Patient under the power of law

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03633188


Contacts
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Contact: Tristan FERRY, Pr 4 72 07 24 81 ext +33 tristan.ferry@chu-lyon.fr

Locations
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France
Hôpital de la Croix Rousse-Service de chirurgie orthopédique Recruiting
Lyon, France, 69004
Contact: Sébastien Lustig, Pr       sebastien.lustig@chu-lyon.fr   
Hôpital de la Croix Rousse-Service des Maladies Infectieuses et Tropicales Recruiting
Lyon, France, 69004
Contact: Tristan FERRY, Pr         
Centre Hospitalier Lyon Sud-Service de Chirurgie Orthopédique Recruiting
Pierre Benite, France, 69310
Contact: Adrien VAN-HAECKE, Dr         
Centre Hospitalier Lyon Sud-Service des maladies infectieuses Recruiting
Pierre Bénite, France, 69310
Contact: Claire Triffault Fillit, Dr         
Contact       claire.triffault-fillit@chu-lyon.fr   
Sponsors and Collaborators
Hospices Civils de Lyon
University of Lyon
Investigators
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Principal Investigator: Tristan FERRY, Pr Hospices Civils de Lyon

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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03633188     History of Changes
Other Study ID Numbers: 69HCL17_0652
2017-A02813-50 ( Other Identifier: ANSM )
First Posted: August 16, 2018    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hospices Civils de Lyon:
Bone and Joint Infections (BJI)
gut dysbiosis
antimicrobial resistance
antibiotic resistance gene
mobile genetic elements

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Bacterial Infections
Anti-Bacterial Agents
Anti-Infective Agents