Assess the Performance of Metagenomic Sequencing in the Diagnosis of STI (NGS-IST)

Sponsor

Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba (Other)

Overall Status

Recruiting

CT.gov ID

NCT05581160

Collaborator

ANRS, Emerging Infectious Diseases (Other)

207

Enrollment

Location

Arm

19.1

Anticipated Duration (Months)

10.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main objective of the study will be to assess the performance of the Next-Generation-Sequencing (NGS) diagnostics of Chlamydia trachomatis and Neisseria gonorrhoeae compared to reference techniques.

Condition or Disease	Intervention/Treatment	Phase
Sexually Transmitted Infections (Not HIV or Hepatitis) Chlamydia Trachomatis Infection Neisseria Gonorrhoeae Infection Mycoplasma Genitalium Infection	Diagnostic Test: Assess the Performance of Metagenomic Sequencing in the Diagnosis of STI (NGS-IST)	N/A

Detailed Description

Sexually Transmitted Infections (STIs) have become a major global public health problem and are among the most common infections. The increase antibiotic resistance, particularly in Neisseria gonorrhoeae and Mycoplasma genitalium, is of concern. Currently, the diagnosis of STIs is based on specific tests by pathogen, mainly by standard culture allowing an antibiotic susceptibility testing, gene amplification tests possibly allowing the search for resistance genes and serologies.

Next-Generation-Sequencing (NGS) is based on the detection and analysis of any DNA and RNA present in the studied sample with a high degree of sensitivity, this method enables the precise identification of non-human sequences regardless its bacterial, viral or parasitologic origin, to detect resistance genes and to characterize the strains.

We propose to assess the performance of NGS for the diagnosis of STIs. We will follow a cohort of 207 PrEP users from Saint-Antoine Hospital every 3 months for 1 year for this purpose.

The main objective of the study will be to assess the performance of the NGS diagnostics of Chlamydia trachomatis and Neisseria gonorrhoeae compared to reference techniques.

The secondary objectives will be (i) to evaluate the performance of the diagnosis by NGS of the other STIs compared to the reference techniques, (ii) to evaluate the interest and the sensitivity of a 3 sites pooled sample "urine, throat and rectum" for the diagnosis of STIs, (iii) to describe the natural history of colonization with Mycoplasma genitalium and the appearance of resistance or pressure of antibiotic selection and (iv) to evaluate the prevalence of agents not usually sought in screening for STI (HSV-1, HSV-2, Haemophilus ducreyi, Campylobacter sp, Shigella sp, Clostridioides difficile, Entamoeba histolytica).

Improved diagnosis of STIs and resistance will allow better patient management.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

207 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

12-months prospective monocentric longitudinal cohort.12-months prospective monocentric longitudinal cohort.

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Assess the Performance of Metagenomic Sequencing in the Diagnosis of STI (NGS-IST)

Actual Study Start Date :

Jul 11, 2022

Anticipated Primary Completion Date :

Feb 11, 2024

Anticipated Study Completion Date :

Feb 11, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 12-month prospective monocentric longitudinal cohort This is a single-arm interventional study. After acceptance of the study (signature of the informed consent form), patients are included in the single-arm interventional study for a period of 12 months with follow-up visits every 3 months (corresponding to standard care for the PrEP users).	Diagnostic Test: Assess the Performance of Metagenomic Sequencing in the Diagnosis of STI (NGS-IST) Proposal of the study to all eligible adult patients coming for pre-exposure prophylaxis (PrEP) consultations from the Infectious and Tropical Diseases Department of Saint-Antoine Hospital (with delivery of a patient's information and signing an informed consent form). The study duration is 12 months. During each visit (D0, M3, M6, M9 and M12), patients will be asked to: Respond to a questionnaire on their history of taking antibiotics, sexually transmitted infections (STIs), their foreign travels, their consumption of tobacco, drugs, alcohol and their sexual practices, Perform the following additional samples: rectal and throat swabs and an urine sample. These samples will be done according to the usual procedures of the center. The diagnosis of STIs (Neisseria gonorrhoeae and Mycoplasma genitalium) will be carried out using 2 techniques: the reference technique and the Next-Generation-Sequencing (NGS) technique.

Arm

Intervention/Treatment

Experimental: 12-month prospective monocentric longitudinal cohort

This is a single-arm interventional study. After acceptance of the study (signature of the informed consent form), patients are included in the single-arm interventional study for a period of 12 months with follow-up visits every 3 months (corresponding to standard care for the PrEP users).

Diagnostic Test: Assess the Performance of Metagenomic Sequencing in the Diagnosis of STI (NGS-IST)

Proposal of the study to all eligible adult patients coming for pre-exposure prophylaxis (PrEP) consultations from the Infectious and Tropical Diseases Department of Saint-Antoine Hospital (with delivery of a patient's information and signing an informed consent form). The study duration is 12 months. During each visit (D0, M3, M6, M9 and M12), patients will be asked to: Respond to a questionnaire on their history of taking antibiotics, sexually transmitted infections (STIs), their foreign travels, their consumption of tobacco, drugs, alcohol and their sexual practices, Perform the following additional samples: rectal and throat swabs and an urine sample. These samples will be done according to the usual procedures of the center. The diagnosis of STIs (Neisseria gonorrhoeae and Mycoplasma genitalium) will be carried out using 2 techniques: the reference technique and the Next-Generation-Sequencing (NGS) technique.

Outcome Measures

Primary Outcome Measures

To evaluate the performance of NGS metagenomic diagnosis of Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng) compared to reference techniques. [12 months]
Sensitivity, specificity, positive and negative predictive values of NGS compared to reference techniques for Ng and Ct.

Secondary Outcome Measures

To evaluate the performance of the diagnosis by NGS of the other STIs compared to the reference techniques. [12 months]
Sensitivity, specificity, positive and negative predictive values of NGS compared to reference techniques for other sexually transmitted infections (STIs).
Describe the epidemiology of circulating strains by molecular typing. [12 months]
Total number of cases of Ct, Ng, agents not usually screened for in STI screening compared to the number of subjects at the time of their inclusion in the study cohort, with 95% confidence interval.
Estimate the incidence and describe the natural history of colonization by Mycoplasma genitalium (Mg). [12 months]
Number of new cases Mycoplasma genitalium (Mg) compared to the number of subjects followed in the study cohort per month of follow-up.
Estimate the incidence of the appearance of Mycoplasma genitalium resistance under antibiotic selection pressure. [12 months]
Number of new cases Mycoplasma genitalium (Mg) compared to the number of subjects followed in the study cohort per month of follow-up under antibiotic selection pressure.
Characterize circulating Neisseria gonorrhoeae (Ng) clones. [12 months]
Total number of cases of circulating Neisseria gonorrhoeae (Ng) clones compared to the number of subjects at the time of their inclusion in the study cohort, with 95% confidence interval.
Characterize the circulating serotypes of Chlamydia trachomatis (Ct). [12 months]
Total number of cases of circulating serotypes of Chlamydia trachomatis (Ct) compared to the number of subjects at the time of their inclusion in the study cohort, with 95% confidence interval.
Estimate the incidence of agents not usually screened for in STI screening (HSV-1, HSV-2, HPV, Mycoplasma hominis, Ureaplasma sp, Haemophilus ducreyi, Campylobacter sp, Shigella sp, Clostridium difficile, Entamoeba histolytica). [12 months]
Number of new cases of agents not usually tested for in STI screening compared to the number of subjects followed in the study cohort per month of follow-up.
Determine the factors associated with STI events. [12 months]
Hazard ratio of determinants (factors) associations with the STI cases incidence.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years old
MSM
PrEP users
Acceptance of study constraints
Affiliated or beneficiary of a Social Security scheme or State Medical Aid
Signature of consent form to participate in the study

Exclusion Criteria:

Language barrier making questioning impossible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Service des Maladies Infectieuses et Tropicales Hôpital Saint-Antoine	Paris		France	75012

Sponsors and Collaborators

Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
ANRS, Emerging Infectious Diseases

Investigators

Study Chair: Karine Lacombe, Pr, PhD, IPLESP INSERM UMR-S1136
Principal Investigator: Laure Surgers, MD, Service des Maladies Infectieuses et Tropicales Hôpital Saint-Antoine