Effect of Antisecretory Factor, Given as a Food Supplement to Adult Patients With Severe Traumatic Brain Injury
Condition: Brain Trauma
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Study type: Interventional
Phase: Phase 3

Summary: 
      The present trial intends to assess whether Salovum®, an egg powder enriched for
      antisecretory factor given to patients with severe traumatic brain injury will improve
      outcome compared to a control group given placebo egg powder.

      100 patients with GCS<9 will be enrolled and randomised to active or placebo treatment during
      maximum 5 days. Salovum® or placebo will be administered orally by nasogastric feeding tubes.

      Primary endpoint will be overall 30 data mortality. Secondary endpoints will be intracranial
      pressure and treatment intensity level.
    

Detailed description: 
      Treatment of increased ICP, using Anti-secretory Factor, in patients with severe head trauma
      Brain edema, defined as an increased fluid content in either the extracellular or
      intracellular space, arise in both trauma and in conjunction with other brain pathologies
      such as infectious diseases, intracranial tumors and ischemic events, i.e. stroke. The
      mechanisms underlying the formation of edema are not fully understood. In the injured brain,
      leakage over the blood brain-barrier arise which leads to transport of fluid from the blood
      to the extracellular space, causing an extracellular or vasogenic edema. Damage to cell
      membranes and disruption of cell function causes an intracellular or cytotoxic edema.
      Although one type of edema may predominate initially, one type most likely leads to another.
      In addition to the physiological, flow-related changes that arise, the edema is also worsened
      by the inflammatory response to damage. In the injured brain, disease associated molecular
      patterns (DAMP), and pro-inflammatory cytokines that can give rise to both intracellular and
      extracellular edema are released.

      If the edema becomes expansive enough to give rise to a significant increase in intracranial
      pressure the circulation of the brain is threatened and surgical intervention inevitable. The
      most common procedure is hemicraniectomy, a procedure intended to add more space for the
      edematous brain to expand. The procedure itself is risky, and re-operations due to hematoma,
      CSF-leakage and more are common. Furthermore, it is not known how the procedure itself
      affects the brain in terms of increased edema, tearing of the brain etc.

      Antisecretory factor, AF is a 41 kDa protein that exists in most mammals. It was first
      discovered due to its ability to inhibit experimental diarrhea. Endogenous AF secretion
      increases after exposure to bacterial toxins and an increase in AF secretion in combination
      with an inflammatory reaction may be a part of normal defense against the secretory and
      inflammatory component in diarrhea and other pathological processes involving membrane
      leakage and inflammation. AF has been shown to modulate pro-inflammatory and anti-
      inflammatory cytokine release. AF has also been shown to be effective against vertigo
      symptoms in Meniere's disease, which is believed to be caused by an abnormal collection of
      lymph around the balance nerve. AF and AF16 (the functional terminal 16 amino-acid peptide)
      have been tested in animal models of cerebral edema such as herpes encephalitis and traumatic
      brain injury with significant reduction of intracranial pressure, morbidity and mortality AF
      is commercially available for human use as Salovum®, an egg yolk powder B221® enriched for
      AF. It is available in pharmacies without prescription, but can also be prescribed as a
      dietary supplement in Sweden. Salovum® is classified as a "medical food" by the Swedish
      Pharmaceutical Agency and the European Union. Salovum® is currently registered in the
      Republic of South Africa.

      Hypothesis Cerebral edema in traumatic brain injury is caused by inflammation triggered by
      tissue damage. The anti-secretory and anti-inflammatory compound Salovum® has the potential
      to counteract this and thus reduce cerebral edema in traumatic brain injury. Furthermore, the
      reduction of cerebral edema is hypothesized to decrease intracranial pressure, reduce the
      development of secondary brain damage and subsequently reduce treatment intensity levels and
      death.

      Aims and Objectives Though, the number of patients with severe traumatic head injury in
      Sweden is decreasing and the need for a larger, randomized trial in a centre with large
      volumes of traumatic brain injury is needed The primary focus for scientific investigation is
      to evaluate if AF given as a dietary supplement (Salovum®) will reduce 30-day mortality in
      adult patients with severe traumatic brain injury. The secondary aims are to investigate
      whether AF will reduce intracranial pressure and treatment intensity levels - TIL, during
      intervention.

      Methodology The outlined study is a phase-2, prospective, double-blinded, randomized,
      placebo-controlled trial. After inclusion patients will be randomized to active Salovum® or
      placebo egg powder treatment every 4th hour during 5 days. Treatment of patients will be
      according to current algorithms at the study site.

      Study population 100 adult (age 18+) patients with severe traumatic brain injury, where
      ICP-monitoring is deemed necessary, will be included in the study.

      Patient samples A venous whole blood sample will be drawn before and after treatment in all
      patients. The blood sample will be frozen and stored at the study site for further analysis.

      Anticipated benefits In an ongoing Swedish study, preliminary results indicate that AF has a
      very potent ICP- lowering effect in patients with severe TBI and other pathologies
      encompassing cerebral edema, which might prove an effect on 30-day mortality in this trial.
    

Intervention name(s): Salovum; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Dietary supplement with high concentration of anti-secretory factor; Placebo for Salovum
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double blinded and prospective.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment