Antisecretory Factor In Severe Traumatic Brain Injury

Study Overview
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Brief Summary
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This study evaluates the addition of Salovum, an egg yolk powder enriched for antisecretory factor, to standard care of participants with severe traumatic brain injury. Half of the participants will be administered Salovum while the other half will be given a placebo egg yolk powder, not enriched for antisecretory factor. Intracranial pressure (ICP), partial brain oxygen pressure (PtbO2), microdialysis of metabolites and inflammatory mediators and trauma intensity level (TIL) will be assessed in all patients.

Detailed Description
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Cerebral edema accounts for an essential part of the morbidity and mortality in severe traumatic brain injury but can also arise in other cerebral pathologies such as infectious and ischemic conditions such e.g. stroke and meningitis. Cerebral edema can lead to an elevated intracranial pressure (ICP) with impact on both perfusion and diffusion in the brain. AF (antisecretory factor) is a 41 kilodalton endogenous and essential protein with proposed antisecretory and anti-inflammatory effects. AF is homologous to S5A and Rpn10 proteins which are parts of the 26S proteasome subunit. AF also shows close homology to angiocidin a protein with reported anti-proliferative and anti-angiogenic properties. The AF protein is cleaved into several active peptides, one of which has been synthesized within a 16 amino acid peptide (AF-16) that has been used in animal experimental studies. Salovum® is a product based on the egg yolk powder B221®, and contains high levels of AF. Salovum® is classified as a food for special medical purposes (FSMP) by the European Food Safety Agency. AF has shown clinical effects in Mb Ménière, mastitis and meningitis. Experimentally AF-16 and AF have been shown to reduce intracranial pressure and improve outcome in models of traumatic brain injury (TBI) and herpes encephalitis. Preliminary results show reduction of ICP and improved outcome in human traumatic brain injury. A randomized, prospective, double-blinded phase 2-3 in participants with severe traumatic head injury is ongoing at Tygerberg University Hospital, Cape Town, South Africa (ClinicalTrials.gov identification number: NCT03339505). The antisecretory factor is an endogenous protein and no antibody formation has been demonstrated in human administration. Although Salovum® has been given to hundreds of patients, no side effects have been recorded. Egg yolk allergy is a contraindication but no cases of triggered allergy have been reported. The mechanisms underlying the effects of antisecretory factor on cerebral edema are not clarified. Immune modulation through effects on myeloid cells, proteasome modulation and effects on ion pumps have been proposed. The present study intends to clarify mechanisms behind the proposed effect of antisecretory factor in cerebral edema In the present study participants with severe traumatic brain injury as defined in inclusion and exclusion criteria will be randomised to either treatment with Salovum or placebo egg powder during 5 days after enrolment. Randomisation will be performed in blocks and randomisation envelopes will be used with the number inside the envelope. Salovum and normal egg powder will be suspended with tap water and administered through the gastric feeding tube. All participants will receive standard care for severe TBI according to the treatment algorithm at the Neuro Intensive Care Unit (NICU), Department of Neurosurgery, Skåne University Hospital, Lund, Sweden. The algorithm prescribes invasive monitoring of ICP, PtbO2 and metabolites (cerebral microdialysis). As this algorithm includes stepwise co-interventions in order to control ICP and cerebral perfusion pressure (CPP) the TIL score will be used to compensate for the bias of increased co-interventions in either arm. At follow up patients will be assessed for mortality and Glasgow Outcome Scale-Extended (GOSE)

Official Title
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Evaluation of Antisecretory Factor in Treatment of Severe Traumatic Brain Injury With Multimodal Monitoring

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Dietary Supplement: Salovum
* Dietary Supplement: Placebo egg yolk powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe traumatic brain injury, Glasgow Outcome Scale (GCS) <9 at admission to NICU. Clinical indication for insertion of intracranial pressure monitor, intracerebral oxygen pressure monitor and microdialysis catheter. Consultation with relatives or consent from guardians. Exclusion Criteria: Known egg yolk allergy. Unilateral or bilateral fixed and dilated pupil after initial operative intervention.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants with severe TBI and scheduled for multimodal monitoring will be randomised to active or placebo treatment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Egg yolk powder not enriched for antisecretory powder | Dietary Supplement: Placebo egg yolk powder<br>* Normal egg yolk powder<br>|
| Experimental: Salovum<br>Egg yolk powder enriched for antisecretory powder | Dietary Supplement: Salovum<br>* Active egg yolk powder<br>* Other names: Antisecretory factor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICP mean | Measured by an intracranial pressure sensor | Change from baseline during intervention | 
| ICP area under curve | Measured by an intracranial pressure sensor | Change from baseline during intervention | 
| ICP mean | Measured by an intracranial pressure sensor | During intervention, 5 days | 
| ICP area under curve | Measured by an intracranial pressure sensor | During intervention, 5 days | 
| Treatment intensity level | Treatment intensity level (TIL) scale. Minimum 0 (no intervention to control intracranial pressure (ICP)), maximum 38 points (maximum efforts to control ICP) | Change from baseline during intervention | 
| Treatment intensity level | Treatment intensity level (TIL) scale. Minimum 0 (no intervention to control intracranial pressure (ICP)), maximum 38 points (maximum efforts to control ICP) | During intervention, 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracerebral oxygen partial pressure | Measured by an intracranial oxygen sensor | Change from baseline during intervention | 
| Intracerebral oxygen partial pressure | Lactate/pyruvate ratio assessed by online microdialysis | During intervention, 5 days | 
| Rate of cerebral metabolism | Lactate/pyruvate ratio assessed by online microdialysis | Change from baseline during intervention | 
| Rate of cerebral metabolism | Lactate/pyruvate ratio assessed by online microdialysis | During intervention, 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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traumatic brain injury, cerebral edema, antisecretory factor, inflammatory cytokines, cerebral oxygen monitoring, intracranial pressure, microdialysis