Dopaminergic disruption induced by traumatic coma: multimodal neuroimaging approaches to characterize dopaminergic pathways abnormalities and biomarkers of recovery using the [18F]LBT-999 radiotracer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut National De La Sante Et De La Recherche Medicale

Participant type

Healthy volunteers, Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

Trial duration

14 Jan 2025 → ongoing

Decision date (initial)

2024-04-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Zionexa SAS · Institut National De La Sante Et De La Recherche Medicale · Union des Blessés de la Face et de la Tête

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Others

To characterize metabolic abnormalities of the dopaminergic network within the striatum in comatose patients with severe traumatic brain (TC-COMA group) injury using the radiotracer [18F]LBT-999.

Secondary objectives 5

1. To characterize metabolic abnormalities in the dopaminergic network throughout the network and within the brainstem, in severe comatose TC patients (TC-COMA group) using the radiotracer [18F]LBT-999.
2. To compare metabolic abnormalities in the dopaminergic network between patients with severe TC with persistent coma (TC-COMA) and severe TC with recovery of response to simple commands at inclusion (TC-ROS).
3. To investigate in all severe TC patients (TC-COMA and TC-ROS) the potential link between: o Structural and metabolic changes in the dopaminergic network ; o Functional and metabolic changes within the dopaminergic network
4. To study in all severe TC patients (TC-COMA and TC-ROS) the motor behavioral signatures of metabolic abnormalities within the dopaminergic network;
5. To determine the prognostic value of structural, functional and metabolic abnormalities within the dopaminergic network in all TC patients (TC-COMA and TC-ROS) on patients' neurological outcome and quality of life at 3 months, 6 months and 1 year.

Conditions and MedDRA coding

Comatose Traumatic Brain Injury patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. For all participants: Female or male between 18 and 65 years of age
2. For all participants: Affiliation with a social security scheme or beneficiary of such a scheme.
3. For all participants: Informed consent signed by the participant or by the trusted person (for patients)
4. 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.
5. For all patients: Discontinuation of sedative treatments for more than 48 hours
6. For all patients: Clinical stability: absence of haemodynamic, respiratory or metabolic failure requiring specific management that contraindicates a medical transfer to the imaging centre.
7. 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.
8. 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).
9. For control subjects: age (+ or - 2 years) and sex matched to patients in the TC-COMA group

Exclusion criteria 10

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 5

1. 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;
2. 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.
3. 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
4. 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.
5. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut National De La Sante Et De La Recherche Medicale

Sponsor organisation

Institut National De La Sante Et De La Recherche Medicale

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

Stein Silva

Public contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

Benjamine Sarton

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications