METHYL (1R,2S,3S,5S)-8-[(E)-4-(18F)FLUORANYLBUT-2-ENYL]-3-(4-METHYLPHENYL)-8-AZABICYCLO[3.2.1]OCTANE-2-CARBOXYLATE for Traumatic brain injury | Traumatic coma

Inclusion criteria

• {"criterion_text":"- For all participants: Female or male between 18 and 65 years of age\n- For all participants: Affiliation with a social security scheme or beneficiary of such a scheme.\n- For all participants: Informed consent signed by the participant or by the trusted person (for patients)\n- For all patients: Patient admitted to hospital, victim of non-penetrating TBI occurring within <30 days: traumatic coma (GCS < 10 with M < 6) on hospital admission.\n- For all patients: Discontinuation of sedative treatments for more than 48 hours\n- For all patients: Clinical stability: absence of haemodynamic, respiratory or metabolic failure requiring specific management that contraindicates a medical transfer to the imaging centre.\n- For the TC-COMA group: Severe TBI, corresponding to prolonged abolition of consciousness - coma- and defined by an initial Glasgow Coma Scale, GCS < 8 with a motor score, M < 6), without return to consciousness (GCS < 10 with M < 6) on the day of inclusion.\n- For the severe TC-ROS group: severe TBI, corresponding to prolonged abolition of consciousness - coma - and defined by an initial Glasgow Coma Scale, GCS < 8 with a motor score, M < 6), with return to consciousness clinically identified by evidence of responses to simple commands (GCS > or = 10 with M = 6).\n- For control subjects: age (+ or - 2 years) and sex matched to patients in the TC-COMA group"}

Exclusion criteria

• {"criterion_text":"- For all participants: Pregnant or breastfeeding woman\n- For control group participants: Women not wishing to maintain effective contraception during the 30-day study period.\n- For all participants: Contraindication to MRI\n- For all participants: Known allergic reaction to PET radiotracer or its excipient\n- For all participants: History of pathology responsible for a disturbance of the dopaminergic system\n- For all participants: Current treatment with a dopaminergic agonist or antagonist effect\n- For all participants: Persons under court protection, guardianship or curatorship\n- For all patients: Coma of origin other than TBI\n- For all patients: Decompressive craniectomy with anatomical changes incompatible with standardized image analysis (midline deviation > 2 cm).\n- For control group participants: Female of childbearing age without effective contraception"}

Primary endpoints

• {"endpoint_text":"- To characterize metabolic abnormalities in the dopaminergic network of patients in the TC-COMA group, the level of [18F]LBT-999 binding to presynaptic dopamine membrane transporters located in the striatum (caudate nuclei and putamen), assessed during PET scans of these patients, will be compared with that of subjects in the control group. This level of binding will be expressed by the average Binding potential (BP) in the striatum.","definition_or_measurement_approach":"Binding level assessed during PET scans, expressed by the average Binding potential (BP) in the striatum (caudate nuclei and putamen). Comparison between TC-COMA group and control group."}

Secondary endpoints

• {"endpoint_text":"- The level of [18F]LBT-999 binding to presynaptic membrane dopamine transporters located throughout the dopaminergic network and brainstem in the patients in the TC-COMA group and subjects in the control group will be assessed by PET scan. This level of binding will be expressed by the mean BP and by the Standard Uptake Value ratio (SUV-r) within each region of interest (ROI) of the dopaminergic network (i.e. striatum, pallidum, substantia nigra) and brainstem, and compared between the groups;","definition_or_measurement_approach":"Assessment by PET; binding expressed by mean BP and SUV-r within ROIs (striatum, pallidum, substantia nigra) and brainstem; comparisons between groups."}
• {"endpoint_text":"- The level of [18F]LBT-999 binding to presynaptic membrane dopamine transporters located at the ROIs defined above and expressed by BP and SUV-r, in patients in the TC-COMA group will be compared to that of patients in the TC-ROS group.","definition_or_measurement_approach":"Assessment by PET; BP and SUV-r in predefined ROIs compared between TC-COMA and TC-ROS patients."}
• {"endpoint_text":"- The links between metabolic changes in the dopaminergic network and structural changes on the one hand, and functional changes on the other, will be established on the basis of parameters collected by PET and MRI in all TC patients (TC-COMA and TC-ROS): o Metabolic changes in the dopaminergic network o Structural changes in white matter o Structural changes in gray matter o Functional changes","definition_or_measurement_approach":"Correlation/association analyses using PET and MRI parameters to link metabolic (PET) changes with structural (MRI white and gray matter) and functional changes."}
• {"endpoint_text":"- Motor behavioral signatures will be assessed in all patients (TC-COMA and TC-ROS) and expressed by the score obtained on the MDS-UPDRS scale.","definition_or_measurement_approach":"Motor behavior measured using MDS-UPDRS scale scores."}
• {"endpoint_text":"- Patients' neurological outcome will be assessed at 3 months, 6 months and 1 year after CT using the CRS-R and DRS (Disability Rating Scale) (35); quality of life using the QOLIBRI","definition_or_measurement_approach":"Neurological outcome assessed at 3, 6, and 12 months using CRS-R and DRS; quality of life assessed with QOLIBRI."}

France

Earliest CTIS Part Ii Submission Date

26-03-2024

Latest Decision Or Authorization Date

22-04-2024

Processing Time Days

27

Number Of Sites

4

Number Of Participants

55

Primary sponsor

Full Name

Institut National De La Sante Et De La Recherche Medicale

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Zionexa SAS","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Institut National De La Sante Et De La Recherche Medicale","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Union des Blessés de la Face et de la Tête","duties_or_roles":"Monetary support","organisation_type":""}