Circulating Cell-Free DNA for Brain Abscess Diagnosis: A Pilot Study (METABCES-PoC)

March 12, 2026 updated by: University Hospital, Grenoble

Assessment of Circulating Cell-Free DNA for the Microbiological Diagnosis of Brain Abscesses: A Pilot Proof-of-Concept Study

Brain abscess is a severe intracranial infection associated with significant morbidity and mortality. Standard management combines neurosurgical intervention, when feasible, with prolonged intravenous antibiotic therapy. Neurosurgical procedures, such as surgical drainage or stereotactic aspiration, play a key role in reducing intracranial pressure, decreasing the infectious burden, and obtaining samples for microbiological identification.

However, neurosurgical intervention is not always possible due to technical limitations or patien related contrindications. In these situations, microbiological documentation becomes particularly challenging. Conventional diagnostic methods have limited sensitivity, with blood cultures and lumbar puncture yielding positive results in only about 25% of brain abscess cases.

Recent advances in infectious disease diagnostics have introduced metagenomic approaches that may improve pathogen detection. Studies have shown that metagenomic analysis of operative samples can provide more comprehensive microbiological documentation than conventional culture-based methods. In addition, next-generation sequencing (NGS) of circulating microbial cell-free DNA in blood enables the detection of short microbial DNA fragments with a short half-life, reflecting active infection. This technology has already demonstrated promising results in clinical situations where microbiological documentation is difficult, such as febrile neutropenia. The present study aims to evaluate the performance of this approach in patients with brain abscess.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Brain abscess is a rare but severe intracranial infection, with an estimated incidence of approximately 0.8 cases per 100,000 individuals and a reported mortality rate ranging from 10% to 20%. Current management relies on a combination of neurosurgical intervention and prolonged intravenous antimicrobial therapy. When feasible, surgical drainage or stereotactic aspiration is performed to reduce intracranial pressure, decrease the infectious burden, and obtain biological samples for microbiological identification of the causative pathogen, enabling targeted antimicrobial treatment.

However, neurosurgical intervention is not always feasible. Technical factors such as small abscess size or deep anatomical location may prevent access to the lesion, and some patients may present contraindications to neurosurgical procedures. In these situations, microbiological documentation becomes particularly challenging. Conventional diagnostic methods, including blood cultures and cerebrospinal fluid analysis, have limited sensitivity in brain abscess and frequently fail to identify the causative pathogen.

Recent advances in molecular diagnostics have led to the development of metagenomic sequencing approaches for pathogen detection. Metagenomic analysis enables the unbiased identification of microbial DNA directly from clinical samples and may provide broader pathogen detection than traditional culture-based techniques. In neurosurgical infections, metagenomic sequencing performed on operative samples has shown promising results and may improve microbiological documentation compared with standard diagnostic methods.

In parallel, sequencing of circulating microbial cell-free DNA (cfDNA) in peripheral blood using next-generation sequencing represents an innovative and minimally invasive diagnostic approach. This technology detects short fragments of microbial DNA released into the bloodstream during active infection and may provide clinically relevant diagnostic information.

This study aims to evaluate the diagnostic performance of circulating microbial cfDNA metagenomic sequencing in patients with brain abscess and to compare its performance with metagenomic sequencing and conventional microbiological cultures performed on intraoperative samples when available.

This pilot study is designed to provide proof-of-concept data on the diagnostic performance of circulating microbial cfDNA sequencing in brain abscess. The results may help define the role of this diagnostic approach in improving microbiological documentation and guiding targeted antimicrobial therapy, particularly when neurosurgical sampling is not feasible.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Grenoble, France
        • CHU de Grenoble Alpes, Laboratoire de bactériologie
        • Contact:
      • Grenoble, France
        • CHU de Grenoble Alpes, Service de réanimation neurochirurgicale
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participant ≥ 18 years of age.
  • Participant presenting with a brain abscess requiring neurosurgical
  • Signed Informed Consent
  • Covered by health insurance

Exclusion Criteria:

  • Participant in exclusion period for another study
  • Participant referred to in articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons : pregnant woman, parturient, breastfeeding mother, person deprived of liberty by judicial or administrative decision, persons undergoing psychiatric care under articles L.3212-1 and L.3213-1 who do not fall under article L.1121-8, persons admitted to a healthcare or social institution for purposes other than research, minors, person under legal protection or unable to express consent).
  • Staff members with a hierarchical relationship to the principal investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Metagenomic Diagnostic Evaluation
Diagnostic test: Plasma Microbial Cell-Free DNA Metagenomic Sequencing
A 20 mL peripheral blood sample will be collected prior to neurosurgical intervention for metagenomic next-generation sequencing (mNGS) analysis of circulating microbial cell-free DNA. Results will be compared with metagenomic analysis and conventional culture of intraoperative brain abscess specimens, which serve as the reference standard for microbiological identification.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Blood and Brain Abscess Metagenomic Concordance
Time Frame: Day 0
Comparison of bacterial species identified by metagenomic next-generation sequencing of cell-free DNA (cfDNA) from blood samples versus metagenomic analysis of per-operative brain abscess samples.
Day 0

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Metagenomic Next-Generation Sequencing vs. Culture Concordance
Time Frame: Day 0
Evaluation of bacterial species identification using metagenomic next-generation sequencing compared to gold-standard culture techniques on per-operative brain abscess samples.
Day 0
Plasma Cell-Free DNA vs. Abscess Culture Correlation
Time Frame: Day 0
Comparison of bacterial species identified by metagenomic analysis of circulating cell-free DNA (cfDNA) from blood samples versus species identified by conventional culture of per-operative brain abscess samples.
Day 0
Potential Clinical Impact on Antimicrobial Treatment
Time Frame: At 1 Month
Assessment of potential therapeutic modifications or antibiotic optimization induced by metagenomic next-generation sequencing results compared to standard culture-based diagnosis.
At 1 Month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Grenoble

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 12, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 18, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 38RC24.0243

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Brain Abscess

Clinical Trials on Plasma Microbial Cell-Free DNA Metagenomic Sequencing

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings