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

Infection, Bacterial Clinical Trial

— GUMIBONE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03633188
• Other study ID #: 69HCL17_0652
• Secondary ID: 2017-A02813-50
• Status: Terminated
• Phase: N/A
• Start date: July 19, 2018
• Est. completion date: August 28, 2020

Study information

• Verified date: February 2021
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: August 28, 2020
• Est. primary completion date: August 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Infection
• Infection, Bacterial

Intervention

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),

Locations

Country	Name	City	State
France	Hôpital de la Croix Rousse-Service de chirurgie orthopédique	Lyon
France	Hôpital de la Croix Rousse-Service des Maladies Infectieuses et Tropicales	Lyon
France	Centre Hospitalier Lyon Sud-Service de Chirurgie Orthopédique	Pierre Benite
France	Centre Hospitalier Lyon Sud-Service des maladies infectieuses	Pierre Bénite

Sponsors (2)

Lead Sponsor	Collaborator
Hospices Civils de Lyon	University of Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in the gut microbiota after treatment	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.	from baseline to week 26
Secondary	Assessment of the evolution of intensity of Diarrheic Symptoms	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)	from baseline to week 8 or week 26
Secondary	Assessment of the evolution of frequency of Diarrheic Symptoms	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)	from baseline to week 8 or week 26
Secondary	Quantity of rectal acquisition of Multi Drug Resistance (MDR) bacteria under antibiotics measured by classic culture and quantification culture methods	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	at week 6 or week 24
Secondary	gut dysbiosis measured by Next Generation Sequencing (NGS)	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.	from baseline to week 26
Secondary	severe post-antibiotic dysbiosis (SPAD) measured by Next Generation Sequencing (NGS)	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.	from baseline to week 26
Secondary	Identification of markers of the gut dysbiosis (inflammatory proteins) measured by Elisa techniques	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.	from baseline to week 26
Secondary	Analysis of impact of Bone and Joint Infection on health-related quality of life in patients by EQ5D5L questionnaires	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.	from baseline to week 26
Secondary	Analysis of impact of Bone and Joint Infection on health-related quality of life in patients by EQ5D3L questionnaire	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.	from baseline to week 26