Traumatic Brain InjuryBBAXNCT03965611
Evolution of Oropharyngeal and Rectal Microbiota After Severe Traumatic Brain Injury
An observational study of Traumatic Brain Injury and Multiple Trauma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Modifications of the human gut microbiota have been associated with different pathological conditions such as obesity, inflammatory bowel diseases and neurodegenerative diseases. Recently the " Brain-Gut Axis ", a bidirectional communication axis between brain and gut, has been described. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Traumatic Brain Injury, Multiple Trauma
- What is being tested?
- Oropharyngeal swab, Rectal swab and Disability rating scale (DRS-F)
- Type of treatment
- Surgery or procedure
- How many people
- 58 participants
- Where
- 1 siteFrance
- Study dates
- 21 Apr 2019to Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients who are 18 years of age or older, admitted to intensive care unit for severe trauma.
Who may be able to join
- Admission to Bicêtre Hospital Trauma Center for severe trauma with:
- either isolated severe traumatic brain injury (TBI): TBI with initial Glasgow Coma Scale (GCS) ≤ 8 and AISextrahead score ≤3; either severe trauma without TBI (AISextrahead score > 3)
- Estimated ICU length of stay 48 hours or more
Who cannot join
- Antimicrobial therapy within the previous 3 months
- Long-term corticosteroids use
- Active cancer
- Institutionalized patient
- Gastro-intestinal perforation or emergency gastro-intestinal surgery following trauma
- Withdrawal of consent
- Patient under guardianship
- Pregnant or breastfeeding women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: From the Brain to the Bugs: Evolution of Oropharyngeal and Rectal Microbiota of Patients With Severe Traumatic Brain Injury Admitted in ICU
Modifications of the human gut microbiota have been associated with different pathological conditions such as obesity, inflammatory bowel diseases and neurodegenerative diseases. Recently the " Brain-Gut Axis ", a bidirectional communication axis between brain and gut, has been described. In recent animal studies, an acute brain injury was associated with rapid modifications of the gut microbiota.
In humans, traumatic brain injury (TBI) is a leading cause of death and disability. The patterns of gut and oropharyngeal microbiota following TBI are unknown. The primary purpose of this study is to characterize gut and oropharyngeal microbiota of patients with severe TBI.
Read the detailed description
Study Protocol :
Observational prospective cohort study.
Patients
Patients admitted to the ICU for severe trauma will be included. Two groups of patients with severe trauma will be studied:
- Patients with isolated severe traumatic brain injury (TBI): TBI with initial Glasgow Coma Scale (GCS) ≤ 8 and AISextrahead score ≤3
- Patients with severe trauma without TBI (AISextrahead score > 3)
A group of healthy individuals will serve as a control population.
Expected total enrollment 20 patients in each group, and 10 healthy controls.
Patient data collection
For each patient, the following data will be collected:
- Demographic data: age, sex, height, weight, ICU admission date, simplified acute physiology score II (SAPS II), injury severity score (ISS), abbreviated injury scale (AIS) at ICU admission.
- Trauma-related data: number and type of trauma-related organ injuries, initial GCS, presence of mydriasis at initial management.
- Factors with potential impact on microbiota: antimicrobial therapy, nutrition type, medications (proton pump inhibitors, opioids, sedations, catecholamines, steroids), surgical procedure during ICU stay.
- Evolution: multidrug resistant bacteria acquisition during ICU stay, ICU acquired-infections. Mechanical ventilation duration, extrarenal epuration, ICU length of stay, neurological outcome evaluated by disability rating scale (DRS-F) at ICU discharge and at 90 days post trauma, death at ICU discharge and 90 days.
Sample collection
Oropharyngeal and rectal swabs will be performed for each patient within the first 24 hours after ICU admission (day 0), then 48 hours (day 2) and 7 days (day 7) after ICU admission and weekly thereafter until ICU discharge. Rectal and oropharyngeal swabs will be performed by trained paramedical staff using sterile swabs with transport medium ESwab® (Becton, Dickinson and Company, New Jersey, USA). Swabs will be stored at -80°C until DNA extraction.
DNA extraction
DNA extraction will be performed using QIAamp PowerFecal Pro DNA® kit (Qiagen®, Courtaboeuf, France) for rectal swabs and Extracta DNA Prep® kit (Quanta Biosciences®, Beverly, USA) for oropharyngeal swabs. DNA will be quantified by Quantit® dsDNA HighSensitivity Assay Kit (Fisher Scientific).
16S rRNA amplification and sequencing
V3 and V4 regions of bacterial 16S rRNA gene sequences will be amplified by polymerase chain reaction (PCR) with universal primers (TCGTCGGCAGCGTCAGATGTGTATAAGAGACAGCCTACGGGNGGCWGCAG and GTCTCGTGGGCTCGGAGATGTGTATAAGAGACAGGACTACHVGGGTATCTAATCC), following the Illumina MiSeq® System protocol (Illumina®). Amplicons will be purified and then sequenced using MiSeq® sequencing system ((Illumina®).
Sequences processing
Sequences processing and operational taxonomic unit (OTU) clustering will be performed using SHAMAN software (SHiny Application for Metagenomic ANalysis) based on R® software (package DESeq2), provided by Pasteur Institute. Taxonomic classification will be performed using SILVA database reference.
Statistical analysis
Statistical analysis will be performed using SHAMAN software (SHiny Application for Metagenomic ANalysis). Bacterial phyla, families and genera repartition will be analyzed, and relative abundance of bacterial genera will be compared between the different populations. Alpha-diversity will be analyzed using different parameters (Shannon index, Simpson's diversity index), as well as beta-diversity (principal component analysis).
The different populations of patients and healthy volunteers will be compared, and the evolution of microbiota along time will be studied.
- Conditions
- Traumatic Brain Injury, Multiple Trauma
- Being tested
- Oropharyngeal swab, Rectal swab, Disability rating scale (DRS-F)
- Keywords
- Traumatic brain injury, Multiple trauma, Microbiota, Intensive care unit
- Medical subject headings
- Brain Injuries, Traumatic, Multiple Trauma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oropharyngeal swabProcedure or surgery
Will be performed by trained paramedical staff using sterile swabs with transport medium ESwab® (Becton, Dickinson and Company, New Jersey, USA). Swabs will be stored at -80°C until DNA extraction.
Rectal swabProcedure or surgery
Will be performed by trained paramedical staff using sterile swabs with transport medium ESwab® (Becton, Dickinson and Company, New Jersey, USA). Swabs will be stored at -80°C until DNA extraction.
Disability rating scale (DRS-F)Procedure or surgery
Will be assessed at day 90 +/- 7 days.
| Study group | Role | What they receive |
|---|---|---|
| Patients with isolated severe traumatic brain injury (TBI) | TBI with initial Glasgow Coma Scale (GCS) ≤ 8 and AISextrahead score ≤3. Oropharyngeal and rectal swabs will be performed for each patient within the first 24 hours after ICU admission (day 0), then 48 hours (day 2) and 7 days (day 7) after ICU admission and weekly thereafter until ICU discharge. Receives: Procedure: Oropharyngeal swab; Procedure: Rectal swab; Procedure: Disability rating scale (DRS-F) | |
| Patients with severe trauma without TBI | Patients with severe trauma without TBI (AISextrahead score > 3). Oropharyngeal and rectal swabs will be performed for each patient within the first 24 hours after ICU admission (day 0), then 48 hours (day 2) and 7 days (day 7) after ICU admission and weekly thereafter until ICU discharge. Receives: Procedure: Oropharyngeal swab; Procedure: Rectal swab; Procedure: Disability rating scale (DRS-F) | |
| Healthy Controls | Persons who have not had the conditions being studied or otherwise related conditions or symptoms, as specified in the eligibility requirements.
Oropharyngeal and rectal swabs will be taken only once, at inclusion, after that the participation of the control individual in the trial will be completed. Receives: Procedure: Oropharyngeal swab; Procedure: Rectal swab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in microbiota alpha-diversity as measured by Shannon index
The oropharyngeal and rectal swabs, performed at day 0, day 2, day 7 after ICU admission and weekly thereafter until ICU discharge or no later than day 90, will be used for DNA extraction and the bacterial 16S rRNA amplification and sequencing in order to identify the bacterial species colonizing the gut.
Measured: From day 0 to day 90
Secondary outcomes (5)
Alpha and beta-diversities of oropharyngeal and rectal microbiota at different times post trauma.
The oropharyngeal and rectal swabs, performed at day 0, day 2, day 7 after ICU admission and weekly thereafter until ICU discharge or no later than day 90, will be used for DNA extraction and the bacterial 16S rRNA amplification and sequencing in order to identify the bacterial species.
Measured: From day 0 to day 90
ICU-acquired infections
The ICU-acquired infection rates during the ICU stay
Measured: From day 0 to day 90
Number of patients acquiring colonization or infection with multidrug resistant bacteria during ICU stay
Multidrug resistant bacteria colonisation or infection acquired during the ICU stay
Measured: From day 0 to day 90
Death at ICU discharge and 90 days post trauma.
The rates of deaths at ICU discharge and 90 days post trauma
Measured: From day 0 to day 90
Disability Rating Scale (DRS-F) score at 90 days post trauma
Neurological outcome at 90 days post trauma evaluated by the Disability Rating Scale, the French translation (DRS-F) quoted from 0 (no disability) to 29 (extreme vegetative state)
Measured: From day 0 to day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2019
- Study start21 Apr 2019
- Primary completion2 Jan 2023
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Université Paris-Saclay
- Responsible party
- Sponsor
- Investigators
- Samy Figueiredo, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03965611
- Sponsor's protocol ID
- APHP180537
- Other IDs
- 2018-A02973-52
- Acronym
- BBAX
- Status last verified
- May 2024
- First submitted
- 24 May 2019
- Last updated
- 30 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- From the Brain to the Bugs: Evolution of Oropharyngeal and Rectal Microbiota of Patients With Severe Traumatic Brain Injury Admitted in ICU
- ClinicalTrials.gov ID
- NCT03965611
- Acronym / sponsor ID
- BBAX / APHP180537
- Conditions
- Traumatic Brain Injury, Multiple Trauma
- Keywords
- Traumatic brain injury, Multiple trauma, Microbiota, Intensive care unit
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Université Paris-Saclay
- Study start
- 21 Apr 2019 (actual)
- Primary completion
- 2 Jan 2023 (actual)
- Study completion
- Dec 2024 (estimated)
- First posted
- 29 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Modifications of the human gut microbiota have been associated with different pathological conditions such as obesity, inflammatory bowel diseases and neurodegenerative diseases. Recently the " Brain-Gut Axis ", a bidirectional communication axis between brain and gut, has been described. In recent animal studies, an acute brain injury was associated with rapid modifications of the gut microbiota.
In humans, traumatic brain injury (TBI) is a leading cause of death and disability. The patterns of gut and oropharyngeal microbiota following TBI are unknown. The primary purpose of this study is to characterize gut and oropharyngeal microbiota of patients with severe TBI.
Detailed description
Study Protocol :
Observational prospective cohort study.
Patients
Patients admitted to the ICU for severe trauma will be included. Two groups of patients with severe trauma will be studied:
- Patients with isolated severe traumatic brain injury (TBI): TBI with initial Glasgow Coma Scale (GCS) ≤ 8 and AISextrahead score ≤3
- Patients with severe trauma without TBI (AISextrahead score > 3)
A group of healthy individuals will serve as a control population.
Expected total enrollment 20 patients in each group, and 10 healthy controls.
Patient data collection
For each patient, the following data will be collected:
- Demographic data: age, sex, height, weight, ICU admission date, simplified acute physiology score II (SAPS II), injury severity score (ISS), abbreviated injury scale (AIS) at ICU admission.
- Trauma-related data: number and type of trauma-related organ injuries, initial GCS, presence of mydriasis at initial management.
- Factors with potential impact on microbiota: antimicrobial therapy, nutrition type, medications (proton pump inhibitors, opioids, sedations, catecholamines, steroids), surgical procedure during ICU stay.
- Evolution: multidrug resistant bacteria acquisition during ICU stay, ICU acquired-infections. Mechanical ventilation duration, extrarenal epuration, ICU length of stay, neurological outcome evaluated by disability rating scale (DRS-F) at ICU discharge and at 90 days post trauma, death at ICU discharge and 90 days.
Sample collection
Oropharyngeal and rectal swabs will be performed for each patient within the first 24 hours after ICU admission (day 0), then 48 hours (day 2) and 7 days (day 7) after ICU admission and weekly thereafter until ICU discharge. Rectal and oropharyngeal swabs will be performed by trained paramedical staff using sterile swabs with transport medium ESwab® (Becton, Dickinson and Company, New Jersey, USA). Swabs will be stored at -80°C until DNA extraction.
DNA extraction
DNA extraction will be performed using QIAamp PowerFecal Pro DNA® kit (Qiagen®, Courtaboeuf, France) for rectal swabs and Extracta DNA Prep® kit (Quanta Biosciences®, Beverly, USA) for oropharyngeal swabs. DNA will be quantified by Quantit® dsDNA HighSensitivity Assay Kit (Fisher Scientific).
16S rRNA amplification and sequencing
V3 and V4 regions of bacterial 16S rRNA gene sequences will be amplified by polymerase chain reaction (PCR) with universal primers (TCGTCGGCAGCGTCAGATGTGTATAAGAGACAGCCTACGGGNGGCWGCAG and GTCTCGTGGGCTCGGAGATGTGTATAAGAGACAGGACTACHVGGGTATCTAATCC), following the Illumina MiSeq® System protocol (Illumina®). Amplicons will be purified and then sequenced using MiSeq® sequencing system ((Illumina®).
Sequences processing
Sequences processing and operational taxonomic unit (OTU) clustering will be performed using SHAMAN software (SHiny Application for Metagenomic ANalysis) based on R® software (package DESeq2), provided by Pasteur Institute. Taxonomic classification will be performed using SILVA database reference.
Statistical analysis
Statistical analysis will be performed using SHAMAN software (SHiny Application for Metagenomic ANalysis). Bacterial phyla, families and genera repartition will be analyzed, and relative abundance of bacterial genera will be compared between the different populations. Alpha-diversity will be analyzed using different parameters (Shannon index, Simpson's diversity index), as well as beta-diversity (principal component analysis).
The different populations of patients and healthy volunteers will be compared, and the evolution of microbiota along time will be studied.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients with isolated severe traumatic brain injury (TBI) | – | Procedure: Oropharyngeal swab, Procedure: Rectal swab, Procedure: Disability rating scale (DRS-F)TBI with initial Glasgow Coma Scale (GCS) ≤ 8 and AISextrahead score ≤3. Oropharyngeal and rectal swabs will be performed for each patient within the first 24 hours after ICU admission (day 0), then 48 hours (day 2) and 7 days (day 7) after ICU admission and weekly thereafter until ICU discharge. |
| Patients with severe trauma without TBI | – | Procedure: Oropharyngeal swab, Procedure: Rectal swab, Procedure: Disability rating scale (DRS-F)Patients with severe trauma without TBI (AISextrahead score > 3). Oropharyngeal and rectal swabs will be performed for each patient within the first 24 hours after ICU admission (day 0), then 48 hours (day 2) and 7 days (day 7) after ICU admission and weekly thereafter until ICU discharge. |
| Healthy Controls | – | Procedure: Oropharyngeal swab, Procedure: Rectal swabPersons who have not had the conditions being studied or otherwise related conditions or symptoms, as specified in the eligibility requirements. Oropharyngeal and rectal swabs will be taken only once, at inclusion, after that the participation of the control individual in the trial will be completed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who are 18 years of age or older, admitted to intensive care unit for severe trauma.
Key inclusion criteria (3 listed)
- Admission to Bicêtre Hospital Trauma Center for severe trauma with:
- either isolated severe traumatic brain injury (TBI): TBI with initial Glasgow Coma Scale (GCS) ≤ 8 and AISextrahead score ≤3; either severe trauma without TBI (AISextrahead score > 3)
- Estimated ICU length of stay 48 hours or more
Key exclusion criteria (8 listed)
- Antimicrobial therapy within the previous 3 months
- Long-term corticosteroids use
- Active cancer
- Institutionalized patient
- Gastro-intestinal perforation or emergency gastro-intestinal surgery following trauma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oropharyngeal swabWill be performed by trained paramedical staff using sterile swabs with transport medium ESwab® (Becton, Dickinson and Company, New Jersey, USA). Swabs will be stored at -80°C until DNA extraction. | Procedure or surgery | Healthy Controls, Patients with isolated severe traumatic brain injury (TBI), Patients with severe trauma without TBI |
| Rectal swabWill be performed by trained paramedical staff using sterile swabs with transport medium ESwab® (Becton, Dickinson and Company, New Jersey, USA). Swabs will be stored at -80°C until DNA extraction. | Procedure or surgery | Healthy Controls, Patients with isolated severe traumatic brain injury (TBI), Patients with severe trauma without TBI |
| Disability rating scale (DRS-F)Will be assessed at day 90 +/- 7 days. | Procedure or surgery | Patients with isolated severe traumatic brain injury (TBI), Patients with severe trauma without TBI |
Primary outcome
Change in microbiota alpha-diversity as measured by Shannon index
Time frame: From day 0 to day 90
The oropharyngeal and rectal swabs, performed at day 0, day 2, day 7 after ICU admission and weekly thereafter until ICU discharge or no later than day 90, will be used for DNA extraction and the bacterial 16S rRNA amplification and sequencing in order to identify the bacterial species colonizing the gut.
5 secondary outcomes
Alpha and beta-diversities of oropharyngeal and rectal microbiota at different times post trauma.
Time frame: From day 0 to day 90
ICU-acquired infections
Time frame: From day 0 to day 90
Number of patients acquiring colonization or infection with multidrug resistant bacteria during ICU stay
Time frame: From day 0 to day 90
Death at ICU discharge and 90 days post trauma.
Time frame: From day 0 to day 90
Disability Rating Scale (DRS-F) score at 90 days post trauma
Time frame: From day 0 to day 90
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2024.
- Individual participant dataSharing planned: Undecided
Related trials for Traumatic Brain Injury
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
RecruitingObservational study
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
Moderate Traumatic Brain Injury
Not yet recruitingPhase 1
Nanopulse Laser Therapy
TBI (Traumatic Brain Injury)
RecruitingObservational study
Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samy Figueiredo, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Traumatic Brain Injury and Multiple Trauma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in microbiota alpha-diversity as measured by Shannon index (time frame: From day 0 to day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2024.