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Coma, TraumaticPhase 2ComaDopaNCT06930261

Dopaminergic Disruption Induced by Traumatic Coma: Dopaminergic Pathways Abnormalities and Biomarkers of Recovery Using MRI and 18F-LBT-999 PET

A Phase 2 study testing LBT-999 in people with Coma, Traumatic, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The neural correlates of consciousness have been studied at the macroscopic level. However, the neurochemical basis of these processes remains poorly understood. The mesocircuit theory challenges the cortico-centric view of consciousness. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Coma, Traumatic
What is being tested?
LBT-999
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
1 siteFrance
Study dates
14 Jan 2025to Sep 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • For All Participants:
  • Aged 18-65 years.
  • Affiliated with or beneficiary of a social security system.
  • Signed informed consent provided by the participant or a trusted representative (for patients).
  • For all TBI Participant
  • Hospitalized for a non-penetrating traumatic brain injury (TBI) occurring within the last 30 days, with traumatic coma (Glasgow Coma Scale (GCS) < 10 and motor score (M) < 6) at hospital admission.
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  • Sedative treatments discontinued for more than 48 hours.
  • Clinically stable (no hemodynamic, respiratory, or metabolic instability requiring specific interventions that contraindicate medical transfer to the imaging center).
  • For the TBI-COMA Group:
  • Severe TBI characterized by prolonged coma, defined as an initial GCS < 10 with M < 6, and no recovery of consciousness at inclusion (GCS < 10 with M < 6).
  • For the TBI-REC Group:
  • Severe TBI characterized by prolonged coma, defined as an initial GCS < 10 with M < 6, with recovery of consciousness evidenced by simple command-following (GCS ≥ 10 with M = 6) at inclusion.
  • For Healthy Controls:
  • Matched by age (± 2 years) and sex to patients in the TBI-COMA group.

Who cannot join

  • For All Participants:
  • Pregnant or breastfeeding women
  • Contraindications to MRI
  • Known allergy to the PET radiotracer or its excipients.
  • History of conditions affecting the dopaminergic system
  • Individuals under legal protection measures
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  • Current treatment with dopaminergic agonists or antagonists.
  • For Patients Only:
  • Coma due to causes other than TBI.
  • Decompressive craniectomy resulting in anatomical alterations incompatible with standardized image analysis (e.g., midline shift > 2 cm).
  • For Healthy Controls Only:
  • Women of childbearing potential without effective contraception.
  • Women unwilling to maintain effective contraception during the 30-day study period.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

BENJAMINE SARTON, MD, PhD contact

+33672346866

benjamine.sarton@inserm.fr

STEIN SILVA, MD, PhD contact

+33689176780

silvastein@me.com

France1 site, 1 recruiting

  • CHU de Toulouse

    Toulouse

    Benjamine SARTON, benjamine.sarton@inserm.fr

    Recruiting

Other trials in France

About this study

Official title: Dopaminergic Disruption Induced by Traumatic Coma: Multimodal Neuroimaging Approaches to Characterize Dopaminergic Pathways Using 18F-LBT-999 PET

The neural correlates of consciousness have been studied at the macroscopic level. However, the neurochemical basis of these processes remains poorly understood. The mesocircuit theory challenges the cortico-centric view of consciousness. It highlights the role of subcortical regulation by dopaminergic circuits, including the ventral tegmental area and striatal loops. Experimental data show the importance of dopamine in consciousness recovery. Animal TBI studies link dopamine deficits to loss of consciousness and recovery. In humans, imaging studies show disrupted dopaminergic networks in chronic consciousness disorders. Yet, early-phase dopaminergic disruptions in acute coma remain underexplored.

Molecular imaging with PET or SPECT offers insights into dopamine system disturbances. The novel radiotracer 18F-LBT-999 enables detailed imaging of dopaminergic circuits, providing better spatial resolution and quantification than SPECT.

Read more

This proof of concept study aims to explore acute subcortical dopaminergic loop disruptions. It will combine 18F-LBT-999 PET with structural and functional MRI in post-traumatic coma.

Methods : Patients with severe traumatic brain injury (TBI) admitted to the intensive care unit state will be evaluated within 30 days post-injury. Participants will undergo clinical assessment after sedation clearance and will be categorized into three groups: (1) TBI-COMA (severe TBI with persistent coma), (2) TBI-REC (severe TBI with recovery of command-following), and (3) healthy controls. All participants will undergo clinical evaluations, anatomical and functional MRI, and molecular imaging: 18F-LBT-999-PET. Neurological outcome (CRS-r scale), Disability rating scale (DRS), Quality of life (QUOLIBRI) and axtrapyramidal symptoms (MDS-UPDRS) will be assessed at 3 month.

Primary Hypothesis: Acute post-traumatic severe TBI patients with persistent coma (TBI-COMA) show reduced presynaptic dopamine receptor levels in the striatum, compared to healthy controls.

Secondary Hypotheses:

  • Dopaminergic disruptions correlate with the severity of consciousness impairment, differentiating TBI-COMA and TBI-REC groups.
  • Structural damage in the striatum and nigrostriatal tract, identified via MRI, aligns with dopaminergic abnormalities.
  • Multimodal imaging findings during the acute phase can predict long-term neurological and quality-of-life outcomes.
  • Characterizing structural, functional, and metabolic variations in dopaminergic networks may guide personalized pharmacological treatments.
Conditions
Coma, Traumatic
Being tested
LBT-999
Keywords
moderate traumatic brain injury, severe traumatic brain injury
Medical subject headings
Coma, Post-Head Injury, Brain Injuries, Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LBT-999Drug

    LBT-999 administration for PET imaging

Study groups in NCT06930261
Study groupRoleWhat they receive
TBI-COMA, TBI-REC, ControlExperimental18F-LBT-999 administration for all participants
Receives: Drug: LBT-999

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Striatal 18F-LBT-999 binding potential

    characterization of dopaminergic network metabolic abnormalities in the TBI-COMA group. This will be assessed by comparing the binding potential (BP) of 18F-LBT-999 to presynaptic dopamine transporters in the striatum (caudate nuclei and putamen) between TBI-COMA patients and healthy controls, as measured by PET imaging

    Measured: 1 year after the end of inclusion

Secondary outcomes (7)

  1. Dopaminergic Network Binding (TBI-COMA vs Controls)

    The BP of 18F-LBT-999 in dopaminergic transporters across the dopaminergic network (striatum, pallidum, substantia nigra) and brainstem (Ventral tegmental area (VTA)) will be assessed via PET in both TBI-COMA patients and healthy controls and compared between these groups

    Measured: 1 year after the end of inclusion

  2. Group Comparisons (TBI-COMA vs. TBI-REC):

    The BP of 18F-LBT-999 in the regions of interest (ROIs) described above will be compared between the TBI-COMA and TBI-REC groups

    Measured: 1 year after the end of inclusion

  3. Structural and Functional Correlations

    Relationships between dopaminergic network metabolic changes (PET) and structural or functional changes (MRI) will be explored in all TBI patients (TBI-COMA and TBI-REC):

    Metabolic Changes: BP of 18F-LBT-999 in dopaminergic network ROIs and brainstem.

    Structural White Matter Changes: Diffusion tensor imaging (DTI) tractography of nigrostriatal pathways, expressed as fractional anisotropy (FA) and mean diffusivity (MD).

    Structural Gray Matter Changes: Voxel-based morphometry (VBM) analysis in predefined ROIs and cortical regions linked to consciousness (e.g., default mode network - DMN: posterior cingulate cortex, medial prefrontal cortex), expressed as gray matter density (GMD).

    Functional Changes: Resting-state functional connectivity in the dopaminergic network and DMN, assessed via BOLD fMRI

    Measured: 1 year after the end of inclusion

  4. Motor Behavioral Signatures

    Motor behavior in TBI-COMA and TBI-REC groups will be evaluated using the Movement Disorders society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS score). A 4-part scale for which the maximum score is 16 points for part 1, 52 for part 2, 108 for part 3, 23 for part 4). A higher score indicates more severe symptoms

    Measured: 1 year after the end of inclusion

  5. Assessment of neurological recovery using the Coma recovery scale (CRS-R)

    Using the Coma recovery scale (CRS-R). It 's a standardized neurobehavioral assessment measure designed for use in patients with disorders of consciousness

    Measured: 3, 6 and 12 months post TBI

  6. Assessment of neurological recovery using the Disability Rating Scale (DRS)

    The Disability Rating Scale (DRS), a 30-point continuous scale that provides quantitative information to document the disability and handicap of the patient, a Higher core indicating more severe disability (i.e unresponsive wakefulness syndrome.

    Measured: 3, 6 and 12 months post TBI

  7. Measering the quality of life with the Quality of Life After Brain Injury scale (QOLIBRI).

    This scale is made of 37 questions, assessing 6 domains of quality of life after a head injury: cognitive, affective, functional, relational, physical and emotional. The questionnaire provides a quality of life profile with a total score. A higher score indicating a better quality of life.

    Measured: 1 year after the end of inclusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2025
  2. Study start14 Jan 2025
  3. Primary completionSep 2027 (estimated)
  4. Study completionSep 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Model description
3 groups: * Control * TBI-COMA (TBI with persistent coma, CGS \<10, motor scale \< 6) * TBI-REC (TBI with consciousness recovery ( i.e. response to order, GCS Motor scale =6)
Masking
None (open label)
Enrolment
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06930261
Sponsor's protocol ID
C22-62
Other IDs
2023-504893-39-00, 2023
Acronym
ComaDopa
Status last verified
May 2026
First submitted
21 Nov 2024
Last updated
8 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LBT-999 in people with Coma, Traumatic, run by Institut National de la Santé Et de la Recherche Médicale, France 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 14 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 8 May 2026. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact BENJAMINE SARTON, MD, PhD (+33672346866, benjamine.sarton@inserm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Striatal 18F-LBT-999 binding potential (time frame: 1 year after the end of inclusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06930261.

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 8 May 2026.

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