A Phase 2 interventional study of LBT-999 in Coma, Traumatic, sponsored by Institut National de la Santé Et de la Recherche Médicale, France. Recruiting at 1 site in France. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-05-08.
Sponsored by Institut National de la Santé Et de la Recherche Médicale, France · Phase 2, Interventional, and Basic science
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.
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:
1,775 studies on the registry are indexed under Brain Injuries, Traumatic; 448 are open to participants now.
This study's planned enrollment of 55 is close to the median of 56 across 1,133 interventional studies indexed under Brain Injuries, Traumatic.
Browse Brain Injuries, Traumatic studies →Institut National de la Santé Et de la Recherche Médicale, France is the lead sponsor of 375 studies on the registry; 82 are open to participants now.
Counted across the registry records on this site, refreshed daily.
For All Participants:
For all TBI Participant
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:
Matched by age (± 2 years) and sex to patients in the TBI-COMA group.
Exclusion Criteria:
For All Participants:
For Patients Only:
For Healthy Controls Only:
18F-LBT-999 administration for all participants
Drug: LBT-999
LBT-999 administration for PET imaging
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
Time frame: 1 year after the end of inclusion
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
Time frame: 1 year after the end of inclusion
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
Time frame: 1 year after the end of inclusion
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
Time frame: 1 year after the end of inclusion
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
Time frame: 1 year after the end of inclusion
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
Time frame: 3, 6 and 12 months post TBI
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.
Time frame: 3, 6 and 12 months post TBI
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.
Time frame: 1 year after the end of inclusion
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Coma, Post-Head Injury
Institut National de la Santé Et de la Recherche Médicale, France