Identification of Sodium Channel Fragments as Serum Biomarkers of a Traumatic Central Nervous System Injury (SpasT-SCI-T)

Identification Des Fragments de Canaux Sodiques Comme Biomarqueurs sériques d'Une lésion Traumatique du système Nerveux Central

Following spinal cord injury (SCI), 75% of patients develop spasticity of the limbs characterized by an increase in muscle tone causing severe pain. Currently, the diagnosis of spinal cord injury is based on clinical and radiological evaluation by CT and MRI, but there is no reliable biomarker capable of predicting the medium and long-term clinical course in terms of emergence and severity of spasticity and neurological recovery. Recently, pre-clinical models in rats have shown the presence of protein fragments from a cleavage of sodium channels in spinal cords below the level of injury. Other studies have also shown the presence of these fragments in the brain following a head injury. These fragments would be potentially useful as a biomarker of the SCI. The detection of sodium fragments would be potentially useful as a biomarker of a lesion of the central nervous system (spinal cord or brain) and of the severity of the spasticity in patients suffering from SCI. The main objective of this study is to detect the presence of sodium fragments in blood samples from patients with SCI from or brain injury. The secondary objectives will be to study the post-lesional / injury kinetics of sodium fragments, to determine their diagnostic values in terms of the severity of the injury, and their prognostic values concerning the emergence of the spasticity in patients with SCI. An initial prospective cohort will include 40 people. The fragments of sodium channels will be measured in blood samples taken within 6 hours post-trauma, then 1, 3, 5 and 7 days post-trauma, as well as 3 and 6 months post-trauma. The overall expression of sodium fragments will be compared to that of healthy controls. Participants will be recruited in the acute care units of the AP-HM. Participants will be recruited from the main acute care units of the AP-HM. Post-traumatic follow-up assessments during their rehabilitation will be carried out at 3 and 6 months in the neurosurgery department of North Hospital from APHM.

Study Overview

• Status: Not yet recruiting
• Conditions: Brain Injuries; Spasticity, Muscle; Spinal Cord Injury
• Intervention / Treatment: Other: Blood sampling

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pierre-Hugues ROCHE; Phone Number: 0033491365135; Email: Pierre-hugues.ROCHE@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

healthy volonteers group: Inclusion Criteria

• Male or Female
• Age 18 to 75
• free of central or peripheral nervous system trauma
• Having given free and informed consent
• Beneficiary of or affiliated to a social security scheme

Exclusion Criteria:

• Pregnant or breast-feeding women
• Person under guardianship or curatorship
• Diagnosis of a neurological disorder
• Diagnosis of a psychiatric disorder
• Diagnosis of a neurodegenerative disease

Spinal Cord injury patients group:

Inclusion Criteria:- Male or female

• Aged 18 to 75
• Beneficiary of or affiliated to a social security scheme
• Having suffered within 6 hours a trauma with an acute LME confirmed according to the following characteristics:
• Lesion located at C4-T12 level and radiologically documented (CT scan and/or spinal MRI performed within 6 hours)
• Complete or incomplete according to the American Spinal Injury Association impairment scale (ASIA A to D)
• Signed consent for emergency and continuation of study

Exclusion criteria:

• Pregnant or breast-feeding patient
• Absence of consent from the volunteer or his/her trusted support person
• Patient under guardianship or trusteeship
• Brain injury due to cranioencephalic trauma with a Glasgow score of less than 14 on reassessment, associated with a cerebral CT scan of grade III or less on the Marshall classification
• Presence of another neurological or mental disorder or neurodegenerative disease

Brain injury patients Group:

Inclusion criteria:

• Male or female
• Aged 18 to 75
• Have suffered a traumatic brain injury (TBI) with a proven acute brain injury according to the following characteristics:
• Glasgow score less than 13 on admission without metabolic cause in the context of head trauma
• Cerebral CT scan at least grade II according to Marshall classification
• Absence of traumatic spinal lesion threatening the integrity of the spinal canal assessed by neuroradiological examination (CT and/or MRI)
• Signed consent for emergency and continuation of study
• ASIA E score

Exclusion criteria:

• Pregnant or breast-feeding patient
• Absence of consent from the volunteer or his/her trusted support person
• Patient under guardianship
• ASIA score A to D
• Presence of another neurological or mental disorder or neurodegenerative disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy volunteers	Other: Blood sampling; Blood sampling to study sodium fragment kinetics
Experimental: Patients with Spinal cord injury	Other: Blood sampling; Blood sampling to study sodium fragment kinetics
Active Comparator: Patients with Brain Injury	Other: Blood sampling; Blood sampling to study sodium fragment kinetics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Detect the presence of sodium fragments in blood samples from patients	6 hours to 6 months post-injury

Secondary Outcome Measures

Outcome Measure	Time Frame
kinetics of sodium fragments in patients with acute SCI and in traumatic brain injury patients in the post-trauma period	6 hours to 6 months post-injury
To correlate measurements of sodium fragments in blood from 6 hours to 6 months post-injury with the occurence of spasticity in the post-trauma period	3 and 6 months-post-injury

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: François CREMIEUX, francois.cremieux@ap-hm.fr

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: July 31, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Craniocerebral Trauma; Trauma, Nervous System; Spinal Cord Diseases; Muscle Hypertonia; Brain Injuries; Wounds and Injuries; Spinal Cord Injuries; Muscle Spasticity
• Other Study ID Numbers: RCAPHM21_0427

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No