The Crosstalk Between the Epigenome and Mitochondria in SCI

NCT06537427 | Not Yet Recruiting

• 1 other identifier: 6884
• Study Type: observational
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

SCI is a devastating neurological disorder for which there are not yet restorative therapies. Thus, there is a need to explore new therapeutic strategies to treat SCI patients. To this end an appropriate selection and enrolment of suitable participants is crucial for the success of the therapeutic protocol. The selection of participants in SCI trials is often based on injury categories (e.g. sensorimotor complete vs incomplete), and neglects biological aspects (e.g. biomarkers released into the CSF and/or blood) that may be amenable to specific therapeutic interventions. On a biomolecular standpoint, it is renown that CNS lacks the ability to sustain a complete regenerative response after damage, which is partially due to the inability of damaged neurons to sustain an epigenetic pro-regenerative response. The background of the present protocol study stands in pre-existing data which showed a crosstalk between the epigenome gene and mitochondria activated upon SCI. The clinical branch of this study protocol aims to investigate if and how targeted proteomic changes following the acute and chronic phase of SCI may play a role in determining the severity of neurologic impairments, as determined with ASIA gradingscale system, at the time of patients' presentation and in the conversion of ASIA grade during follow-up. A previous pilot study conducted by Wichmann et al. has shed light on proteomics after SCI enabling a profiling of inflammatory responses after spinal cord injury, timing of proteomics changes involved in inflammatory responses and differences between proteins title in CSF and peripheral blood. On the other hand, authors failed to prove a correlation between inflammatory proteins expression and timing of expression and neurologic status. However, previous studies proved that proteome expression variations SCI-induced can be detected into patients' CSF and serum and that biomarkers released into the CSF and/or blood may provide a plethora of information as to the patients' biological response to SCI. These samples may contain a unique fingerprint that can be used by scientists and clinicians to elucidate the mechanisms underlying irreversible central nervous system (CNS) degeneration following SCI. This could allow treatments to target specific molecules which promote CNS degeneration. Within this context the identification of prognostic biomarkers of SCI will help to assign SCI patients to the correct therapeutic treatment that, in association with canonical therapies, may synergistically act to improve functional recovery. The aim of the present study is to investigate the presence of prognostic markers in SCI patient-derived serum and CSF with respect to a control group of healthy patients.

Conditions

Injury, Spinal Cord

Outcome Measures

Primary Outcomes (1)

• Changes from baseline in the proteome profile in serum and CSF samples of SCI patients

  To evaluate molecular variations in CSF and/or serum SCI-derived patients, both in acute and chronic phase after injury, patients with acute SCI will be enrolled and they will be followed until the chronic stage. CSF and serum biomarkers of SCI-group will be compared to those of the control group (non-SCI group) undergoing spinal anesthesia for lower limbs orthopedic surgery, in which few milliliters of CSF and serum will be collected.

  Months 1-24

Secondary Outcomes (1)

• Correlation of the proteome profile of SCI patient's with their clinical profile.

  Months 1-24

Study Arms (2)

Control group/CTRL

Healthy adults undergoing spinal anesthesia for lower limbs orthopaedic surgery.

Other: Data collection

Patients with an acute spinal cord injury/SCI

Patients with an acute, traumatic SCI

Other: Data collection

Interventions

Data collection OTHER

The data to be collected are the following: * Demographic data: gender and age of the patient at diagnosis of SCI; * Drug assumption and drug abuse at the time of SCI; * A complete assessment of patients' comorbidities; * Complete neurological examination on admission and at 6-8 months follow-up according to ASIA protocol; * Neuro-radiological data: spinal CT and MRI performed within 48 hours of admission to document the type, level and extent of the lesion of the spine and the spinal cord; * CSF pressure, chemical and biological markers; * Serum chemical and biological markers; * Data coming from surgical procedure: type of decompression, type of stabilization, extension of the stabilization, surgical approach, staged surgery, timing of surgery, length of surgery, eventual intraoperative, postoperative or long-term surgical-related complications \[13\]; * Data on hospitalization: length of stay, hospital-acquired infections, any adverse event occurred during hospitalisation.

Control group/CTRL; Patients with an acute spinal cord injury/SCI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

SCI patients will receive at admission an intrathecal lumbar drain below L2, that will remain in place for 5 days. Intensive care clinical setting will allow MAP continuous monitoring, whose augmentation above 85 mmHg is a well-established standard of care in SCI patients. CSF drainage will be employed for 5 days maintaining intrathecal pressure at a mean value of 5.3 mmHg with respect to the CTRL group in which the intrathecal pressure had a mean value of 15 mmHg .Lumbar intrathecal insertion will have the dual clinical objective of 1) monitoring CSFP for evaluation of SCPP and 2) collecting CSF samples if needed in order to reduce CSFP and to keep SCPP above 85 mmHg. 3 ml of blood serum will be collected daily for exams.

You may qualify if:

• ASIA impairment scale grade A, B, or C upon admission;
• neurological level of injury between C1-L1;
• patient older than 18 years;
• ability to collect a valid, reliable baseline neurologic examination within 24h of injury.

You may not qualify if:

• Concomitant TBI;
• major axial or appendicular trauma;
• in case of sedation or intoxication making unreliable the neurological examination.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Data Collection

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: August 5, 2024
• Study Start: August 30, 2024
• Primary Completion: August 30, 2025
• Study Completion (Estimated): August 30, 2026
• Last Updated: August 28, 2024

Record last verified: 2024-07