Clinical trial NCT03818451: Co-ultra PEALut Enhances Neuronal Recovery Following Moderate Traumatic Brain Injury
Official title: Co-ultra PEALut Enhances Neuronal Recovery Following Moderate Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Traumatic Brain Injury
Keywords: Moderate brain trauma
Glialia
Neuroinflammation
Neuroprotection
Lead sponsor: University of Messina
Sponsor class: OTHER
First posted: 2019-01-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Traumatic brain injury (TBI) typically provokes secondary injury mechanisms, including the dynamic interplay between the ischemic, inflammatory, and cytotoxic processes. Moreover, such an impact induces a substantial level of cell death and results in the degeneration of the dendrites, thereby leading to persistent motor, sensory, and cognitive dysfunction. Previous studies have shown that the adult-born immature granule neurons in the dentate gyrus are the most susceptible of all the cell types in the hippocampus to damage following a moderate TBI due to a controlled cortical impact (CCI) device. Currently, there is no efficient approach available for avoiding immature neuron death or degeneration following TBI. Hence, this study aimed to assess the neuro-regenerative properties of co-ultramicronized PEALut (Glialia®), which is composed of palmitoylethanolamide (PEA) and the flavonoid luteolin (Lut), in an in vivo model of TBI, as well as in patients affected by TBI.

Detailed description: Study Setting All patients affected by moderate TBI (Glasgow Coma Score 9-13) admitted to the neurosurgical department of the University Hospital of Messina, Italy, will be screened for recruitment.

Ethics The institutional review board (IRB) approved the study. Written consent will be obtained from each patient or the closest family member prior to the start of the study.

Study Design A randomized controlled single-blind study to assess the effects of co-ultraPEALut (Glialia®) administration in TBI patients will be carried out. The study is set to recruit at least 30 patients.

Recruited patients are randomly allocated to one of the two branches of the study: standard TBI treatment + Glialia® (Study Group) and standard TBI treatment (Control Group) in a 1:1 ratio using precompiled randomization tables.

General treatment

All patients will undergo standard treatments according to patterns of severity and in the light of distinct variables, mainly represented by the conditions of cerebral hemodynamics. These procedures can be summarized as follows:

* Surgical evacuation of hemorrhagic masses and / or "debridement" of outbreaks brain contusion;
* Medical management aimed to maintenance of euvolemia and adequate brain perfusion. Goals were a systolic blood pressure \>90 mmHg and a cerebral perfusion pressure \>60 mmHg. Prevention of secondary complications of critical illness included: preventive therapy of venous thromboembolism (VTE) using low molecular weight heparin (LMWH) and seizures using levetiracetam prophylactically for the first seven days after injury;
* Patient who underwent surgical treatment, received also postoperative intensive care treatments including: position of the head high, lower values of end-tidal CO2, sedation with reduced metabolic consumption of O2, increase in plasma osmolarity by administration of mannitol in controlled doses or hypernatremia, therapeutic CSF drainage.

Specific Treatment The investigations agent, the co-ultraPEALut, will be administered orally twice daily (every 12 h) for 180 days in association with the specific therapy (e.g., antiplatelet agents, anticoagulants, antiepileptic drugs) commonly administered to these patients and/or with drugs prescribed for comorbidities (i.e. diabetes, arterial hypertension).

Eligibility criteria: Inclusion Criteria:

* Traumatic brain injuries
* Moderate trauma
* Glasgow Coma Score 9-13
* Loss of consciousness lasting \>1 min
* post-traumatic amnesia \>20 minutes
* CT scan Marshall Scale class II-VI.

Exclusion Criteria:

* Spinal cord injuries
* Pre-existing neurological disorders affecting the brain and/or the spinal cord
* Severe hypertension
* Diabetes, and chronic renal disease
* Remarkable chronic cerebravasculopathy of the CT
* Severe cognitive deficit.

Primary outcomes:
measure: Cognitive outcome assessed Mini Mental State Examination (MMSE)
timeFrame: All patients will undergo neurological and neuropsychological evaluations at baseline (T0), after 30 days (T30) and 6 months (T180)
measure: Cognitive outcome assessed by the Brief Neuropsychological Cognitive Examination (BNCE)
timeFrame: All patients will undergo neurological and neuropsychological evaluations at baseline (T0), after 30 days (T30) and 6 months (T180)
measure: Depression outcome assessed by Beck Depression Inventory
timeFrame: Outcome measure will be assessed at 180 days (T180) after trauma
measure: Assessment of Independence by Barthel Index
timeFrame: Outcome measure will be assessed at 180 days (T180) after trauma
Secondary outcomes:
Other outcomes:
Locations:
city: Messina
country: Italy
facility: Department of Neurosurgery, University of Messina
Study officials:
References: